Consensus document for the use of the Polypill in the secondary prevention of cardiovascular disease

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Results from major randomized controlled clinical trials and Registry studies. (A) Randomized controlled trials. (A.1) Phase 3 placebo-controlled clinical trial for agalsidase beta (total patients randomized: 58, follow-up 6 months). Endothelial deposits in kidney biopsies.<a class="elsevierStyleCrossRef" href="#bib0280">25</a> (A.2) Phase 2 placebo-controlled clinical trial for agalsidase alfa (total patients randomized: 26, follow-up 6 months). Endothelial deposits in kidney biopsies.<a class="elsevierStyleCrossRef" href="#bib0275">24</a> (A.3) Phase 4 placebo-controlled clinical trial for agalsidase beta (total patients randomized: 82, follow-up 3 years). Severe kidney, cardiac, central nervous system events or death.<a class="elsevierStyleCrossRef" href="#bib0285">26</a> (A.4) Phase 4 head-to-head controlled clinical trial for agalsidase beta versus alfa (Canadian Fabry Disease Initiative, total patients randomized: 114, sample size calculation: >600, follow-up 8 years). Severe kidney, cardiac, central nervous system events or death (http://garrodsymposium.com/garrod2016/posters/#p104; accessed July 18, 2016). (B) Registry data. Fabry Registry, patients treated with agalsidase beta. Severe kidney, cardiac, central nervous system events or death.<a class="elsevierStyleCrossRef" href="#bib0290">27</a> Incidence of severe clinical events in first 6 months of ERT compared to next 5 years (1044 patients, follow-up 5 years). Note that as patients get 5 years older during the study, an increased incidence rate of events would be expected but the opposite was observed. S In all trials ERT was used at label dose: 0.2mg/kg/2 weeks for agalsidse alfa and 1.0mg/kg/2 weeks for agalsidase beta. * Statistically significant difference, n.a. Not available, given the nature of the study. 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] ] 13 => array:3 [ "nombre" => "José Juan" "apellidos" => "Alemán" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 14 => array:3 [ "nombre" => "Isabel" "apellidos" => "Egocheaga" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Sociedad Española de Cardiología, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Sociedad Española de Medicina Interna, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Sociedad Española de Medicina de Familia y Comunitaria, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Sociedad Española de Médicos Generales y de Familia, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Sociedad Española de Médicos de Atención Primaria, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Documento de consenso del uso clínico de la Polypill en la prevención secundaria del riesgo cardiovascular" ] ] "textoCompleto" => "IntroductionCardiovascular diseaseCardiovascular disease (CVD) includes ischemic diseases of heart, brain and peripheral vascular system. Its main substrate is atheromatosis, a chronic disorder that develops insidiously throughout life and is usually advanced when the first symptoms appear.<a class="elsevierStyleCrossRef" href="#bib0625">1</a> CVD often begins with an acute episode due to an atherothrombotic complication in the form of acute coronary syndromes (including sudden death in 15–20% cases) and stroke, as major manifestations.<a class="elsevierStyleCrossRef" href="#bib0630">2</a> The fact that the first (or successive) clinical manifestations may be lethal or highly disabling emphasizes the need for primary and secondary prevention.Although cardiovascular (CV) mortality has dropped considerably in recent decades in many European countries, CVD causes 4 million deaths in Europe every year and over 1.9 million deaths in the European Union. Therefore, it is the major cause of premature death. 40% of all deaths in the European Union are due to CVD,<a class="elsevierStyleCrossRef" href="#bib0630">2</a> while in Spain they account for 30.3% of all deaths, being the leading cause of death.<a class="elsevierStyleCrossRef" href="#bib0635">3</a>CVD causes a high number of disability cases and will continue to be the major cause of loss in productivity.<a class="elsevierStyleCrossRef" href="#bib0625">1</a> In Spain it is estimated that health care costs of CVD will increase from 5.9 million euros in 2014 to 8.8 million euros in 2020, with hospitalization being responsible for approximately 50% of health care costs.<a class="elsevierStyleCrossRef" href="#bib0640">4</a>CVD is strongly related to lifestyle, especially with smoking, unhealthy eating habits, physical inactivity and psychosocial stress.<a class="elsevierStyleCrossRef" href="#bib0645">5</a> The chronicity of these patients is a determinant in the decision making regarding their follow-up and treatment. The high rates of rehospitalization and morbidity and mortality in the short term after hospital discharge in patients treated on CV events show the need to stress on the help and follow-up required by these patients after discharge. CVD prevention is key to stop the occurrence of CVD, and is defined as a series of coordinated actions, both in population and individuals, aimed at eradicating, eliminating or minimizing the impact of CVD and their associated disability.<a class="elsevierStyleCrossRef" href="#bib0625">1</a> Prevention is typically defined as primary prevention and secondary prevention. However, in CVD distinction between these two categories is arbitrary because of the underlying and progressive nature of the atherosclerotic process.<a class="elsevierStyleCrossRef" href="#bib0625">1</a>For understanding the dynamics of the CV epidemic it is important to differentiate between the effect of a decrease in mortality and changes related to the prevention of clinical episodes. It has been shown that prevention of CVD through various lifestyle and pharmacological preventive strategies works. Specifically, over 50% of the reduction in CV mortality is related to the modification of risk factors and 40% to the improvement of treatments.<a class="elsevierStyleCrossRef" href="#bib0625">1</a> In spite of this, in the developed countries the application of these preventive measures is much lower than expected. One of the aspects to improve is the lack of therapeutic compliance of patients, which limits the potential benefit that might be obtained through prevention.Concept of adherence to therapyThe World Health Organization defines the adherence to a long-term therapy as the degree of adherence to the pharmacological treatment, the follow-up of a diet and/or changes in lifestyle to comply with the recommendations agreed upon with the doctor or other health professionals.<a class="elsevierStyleCrossRef" href="#bib0650">6</a> Thus, adherence involves both taking the medication properly (in accordance with the prescribed dosage and schedule) and lifestyle modifications over time. And, unlike compliance, implies the patient's active participation.<a class="elsevierStyleCrossRefs" href="#bib0650">6–8</a> Adherence to therapy is a complex behavior process that has been defined as: “An active, voluntary and collaborative involvement of the patient in a course on behavior to produce a therapeutic result”.<a class="elsevierStyleCrossRef" href="#bib0665">9</a>It is estimated that the number of patients with good adherence in secondary prevention of CVD is generally low and that it decreases progressively over time.<a class="elsevierStyleCrossRefs" href="#bib0670">10–12</a> On average, after 6 months of effective treatment, over 50% patients decide to suspend their treatment and lifestyle modifications.<a class="elsevierStyleCrossRef" href="#bib0685">13</a> The lack of adherence to therapy, and therefore, not complying with the therapeutic goals, has a high impact on the health of the patient and entails a high economic cost due to the increase of hospitalization and death rates.<a class="elsevierStyleCrossRef" href="#bib0690">14</a> There are many reasons leading to the lack of adherence to pharmacological treatment<a class="elsevierStyleCrossRefs" href="#bib0685">13,15–18</a> such as those related to the patient's own personal situation, chronicity and the asymptomatic character of the disease itself, the lack of doctor–patient communication, or lack of accessibility to medical services, etc.The direct association between adherence to the prescribed pharmacological treatment and the degree of control of chronic diseases and the incidence of CV episodes, leading to higher or lower morbidity and mortality, is currently known.<a class="elsevierStyleCrossRefs" href="#bib0715">19,20</a> Lack of adherence to therapy is a major global problem in both developed and developing countries<a class="elsevierStyleCrossRef" href="#bib0725">21</a> and is one of the obstacles to improving patients’ health and quality of life and reducing costs of Health and Social care.<a class="elsevierStyleCrossRef" href="#bib0730">22</a> Support instead of blaming the patient, simplifying treatment, better doctor–patient communication and a multidisciplinary approach taking into account the preferences of the patient, might provide solutions tailored to each individual case.PolypillPreventing CVD by using fixed-dose combination therapies has gained increasing momentum as a strategy to stop the progression of the disease. Including key medications necessary to reduce cardiovascular risk (CVR) in a single capsule or tablet, once-daily, can improve adherence to therapy.<a class="elsevierStyleCrossRef" href="#bib0735">23</a> The results of clinical trials have supported the viability of these therapies in the prevention and management of CVD although with some warnings, essentially related to the lack of evidence on the effect of these therapies to effectively reduce CV events. There are currently several ongoing clinical trials that will provide definitive evidence on the effectiveness of these combinations.<a class="elsevierStyleCrossRef" href="#bib0690">14</a>The Polypill for secondary prevention of CVD is the first fixed-dose combination therapy approved in Europe indicated for the secondary prevention of CV events as a replacement treatment in adult patients adequately controlled with the monoingredients administered concomitantly in equivalent therapeutic doses. The capsule includes 3 active ingredients: acetylsalicylic acid (ASA) 100mg, atorvastatin 20mg and ramipril 2.5, 5 or 10mg. In Spain, its price includes the price of its 3 ingredients.<a class="elsevierStyleCrossRef" href="#bib0740">24</a>Purpose of the consensus document and field of applicationThe purpose of this consensus document is to define and recommend, through evidence available in the literature and the opinion of health professionals, the impact of non-adherence to therapy for secondary prevention of CVD and the potential use of a Polypill in the daily clinical practice of these patients; Without forgetting that the use of a fixed-dose combination therapy should not make ignore the need to maintain an adequate lifestyle.The recommendations in this document are aimed at all those specialists, cardiologists, internists and primary care practitioners authorized to prescribe and monitor patients with high and very high CVR and requiring secondary prevention of CVD, or high-risk patients, or very high CVR requiring treatment with antiplatelet, hypolipidemic and antihypertensive drugs.Methodology used in the documentThe consensus was performed using RAND/UCLA methodology.<a class="elsevierStyleCrossRef" href="#bib0745">25</a> This consensus method is based on the scientific evidence and the collective judgment and clinical experience of a panel of experts. The purpose of this method is to promote the critical discussion of experts, through the individual reflection of a questionnaire and a new group discussion on the consensuses and disagreements reached in the individual reflection, through a face-to-face, structured and participatory session. In order to define the degree of acceptance of the recommendations, a percentage agreement was established. The recommendations were classified as “unanimously accepted” if the entire panel of experts agreed, “accepted by consensus” if over 80% agreed “in discrepancy”, accepted by 66–79% and “rejected” when it was approved by less than 66%.Finally, a final recommendation report was drafted. This document included both the agreements and disagreements after the consensus phase. The recommendations were accompanied by the final percentage agreement obtained in the last vote. The final report was validated and approved by the participants.In order to evaluate the levels of scientific evidence and degrees of recommendation, the modified SIGN method<a class="elsevierStyleCrossRef" href="#bib0750">26</a> was used, using the Oxford Centre for Evidence-Based Medicine system<a class="elsevierStyleCrossRef" href="#bib0755">27</a> for diagnostic questions and the SIGN system for the remaining questions (treatment, prognosis, etc.) (<a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>). In addition, whenever possible, AGREE<a class="elsevierStyleCrossRef" href="#bib0760">28</a>was used when drafting the document.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>RecommendationsImpact of lack of adherence on cardiovascular healthThe non-symptomatic and chronic nature of CVD, drug co-payment, complex therapeutic schedules or not in accordance with current clinical practice guidelines and the lack of educational programs for professionals and patients<a class="elsevierStyleCrossRef" href="#bib0655">7</a> would explain, among other causes, the lack of adherence to therapy and perpetuity of CVD as the main cause of global morbidity and mortality in a setting with high economic cost. The increase in the rate of major CV events,<a class="elsevierStyleCrossRefs" href="#bib0765">29–31</a>the increase in healthcare burden and in health costs<a class="elsevierStyleCrossRef" href="#bib0780">32</a>are the consequences of this lack of adherence to therapy (LE: 2+).The lack of adherence to therapy results in a higher CV morbidity and mortality, both in primary and secondary prevention of CVD,<a class="elsevierStyleCrossRefs" href="#bib0765">29–31</a> as well as a higher rate of hospital admissions and readmissions.<a class="elsevierStyleCrossRefs" href="#bib0775">31,33</a>Therefore, lack of adherence to therapy has been shown to increase the rate of major CV events, both in primary (LE: 2+) and secondary prevention of CVD (LE: 1−), which implies poorer quality of life for patients.<a class="elsevierStyleCrossRefs" href="#bib0765">29–31,33</a>On the other hand, within the CVR, CVD implies risk factors, related clinical conditions, or comorbidities,<a class="elsevierStyleCrossRefs" href="#bib0785">33,34</a> such as hypertension (HT), dyslipidemia or diabetes mellitus. Thus, non-adherence to therapy for one of these conditions may lead to non-adherence to other therapies. There is also evidence that non-adherent patients are less likely to attend medical visits,<a class="elsevierStyleCrossRefs" href="#bib0790">34,35</a> which would imply the loss of possibilities for an early (and opportunistic) diagnosis of other CVR-related or non-CVR-related diseases.The frequency of medical visits is directly related to adherence to therapy, which is greater in patients with a higher number of medical visits with a prescription.<a class="elsevierStyleCrossRef" href="#bib0790">34</a> The patient's lack of confidence in initiating a new therapy may lead to a lower number of visits to the physician.<a class="elsevierStyleCrossRefs" href="#bib0655">7,36</a> In addition, patients non-adherent to their treatment, due to lack of trust/communication with their doctor, usually do not attend or attend fewer visits compared to adherent patients.<a class="elsevierStyleCrossRef" href="#bib0795">35</a>Despite this, the lack of adherence to therapy increases the burden of care due to the greater complexity of complications and hospital admissions<a class="elsevierStyleCrossRef" href="#bib0690">14</a> (LE: 1++).Likewise, non-adherence to pharmacological therapy entails a high cost of healthcare arising mainly from hospitalization (which accounts for approximately 50% of the cost) and, secondly, pharmaceutical costs.<a class="elsevierStyleCrossRefs" href="#bib0640">4,7,33</a> Furthermore, it is a major cause of the inefficient healthcare system<a class="elsevierStyleCrossRefs" href="#bib0640">4,7</a> because of the increase in direct costs as a result of CVD (costs of admission, emergency visits, outpatient hospital care, etc.) and the increase in indirect costs (early mortality and morbidity).It is important to emphasize the need for studies that evaluate the cost-effectiveness not only of treatment, but also of pharmacological interventions, which has been termed as the “size of treatment effects”.<a class="elsevierStyleCrossRef" href="#bib0775">31</a> The available studies do not really reflect the magnitude of the problem because they evaluate the cost-effectiveness of a particular treatment, regardless of compliance, or because they fail to investigate the effect size, particularly because compliance and effectiveness of treatment are unknown. Thus, adherence is a key factor in ensuring the sustainability of the healthcare system, since non-adherence is linked to poorer health outcomes and higher costs for the system<a class="elsevierStyleCrossRefs" href="#bib0640">4,7,33</a>(LE: 2++).Adherence to therapy in secondary prevention and in patients of high, or very high risk with subclinical cardiovascular diseaseDespite all improvements in both the therapeutic and the CVD outcomes, the lack of adherence to medication indicated in chronic diseases continues to be an important barrier in the secondary prevention of CVD.<a class="elsevierStyleCrossRef" href="#bib0675">11</a>The lack of time and resources devoted to the patient's health education, the difficulty of access to cardiac rehabilitation programs, the awareness of the physician and the patient self-awareness of the disease and care are factors that determine the lack of adherence in secondary prevention and in high or very high risk patients with subclinical CVD.Adherence to therapy is more closely correlated with the type of disease or therapeutic schedule than with the patient's demographic characteristics (age, sex, education, and income level).<a class="elsevierStyleCrossRef" href="#bib0710">18</a> Several studies have shown low adherence in different patient profiles. Thus the FOCUS study<a class="elsevierStyleCrossRef" href="#bib0695">15</a> concludes that the low adherence to a complex pharmacological treatment of patients who have suffered an acute myocardial infarction is associated with a young age and depression. (LE: 1++). In terms of secondary prevention, poor adherence has been reported in: elderly, unemployed patients, with higher comorbidity, polypharmacy, multivascular disease, non-interventional treatment, etc.<a class="elsevierStyleCrossRefs" href="#bib0675">11,37–39</a> (LE: 2−). Patients who have suffered an acute coronary syndrome or an intervention are more adherent than those who have suffered a stroke, probably due to the cognitive/physical worsening associated with the latter. In addition, some authors show that non-adherence to medication in patients with post-traumatic stress arising from stroke may be due to concern or fear of drugs<a class="elsevierStyleCrossRef" href="#bib0820">40</a> (LE: 2−). <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> lists the recommendations on these determinants.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Actions to measure adherence to therapyIt is crucial to be provided with reliable methods for measuring and evaluating adherence to therapy efficiently, so that the necessary preventive and/or corrective actions can be taken.A great variety of strategies have been described to assess the therapeutic adherence of patients with chronic diseases, although their specific measurement shows many difficulties.<a class="elsevierStyleCrossRef" href="#bib0710">18</a> Most studies conducted to evaluate strategies aimed at improving adherence measures overestimate the degree of adherence.<a class="elsevierStyleCrossRefs" href="#bib0825">41,42</a> Direct and indirect methods have been described and applied. The former are poorly applicable to standard clinical practice and the latter are simpler and more applicable, but limited because of their low sensitivity and moderate specificity.Direct methods for assessing pharmacological adherence (such as blood or urine drug levels, direct observation of intake, etc.) are expensive, complex and poorly applicable to routine clinical practice. Therefore, their use is practically relegated to the field of research.<a class="elsevierStyleCrossRefs" href="#bib0835">43,44</a> (LE: 4).The most simple indirect method is the method based on the opinion of the professional. However it has been proven not sufficiently valid as the only tool to assess adherence, not only because of the subjectivity that it entails, but mainly because of the deficiencies in doctor–patient communication. 74% physicians believe their patients are taking the prescribed medication and 83% patients do not inform their practitioner about their adherence to therapy. Therefore, there is little agreement between doctors’ perception on the quality of their communication with their patients and the actual information that the patients report to their doctor.<a class="elsevierStyleCrossRefs" href="#bib0845">45,46</a> (LE: 2+).The indirect method based on the counting of tablets compares the number of tablets remaining in the package in a scheduled appointment, taking into account the prescribed tablets and the time elapsing between the prescription and the counting, and thus obtain the compliance rate considering 80–110% as good adherence.<a class="elsevierStyleCrossRefs" href="#bib0835">43,47</a> For some authors it is considered as a reference method.<a class="elsevierStyleCrossRef" href="#bib0860">48</a> It can be used to confirm suspected noncompliance, but it has the limitation that when the patients are feeling observed, they improve their adherence. Specific devices for the counting of tablets are currently available (Monitors Events Medication Systems) which are containers recording every opening and are subsequently analyzed by computer (LE: 2+).Another indirect method widely recommended is the personalized clinical interview. The technique usually used is self-test questionnaire. The most used tests are the Haynes and Sackett test,<a class="elsevierStyleCrossRef" href="#bib0865">49</a> the Moriski–Green–Levine test<a class="elsevierStyleCrossRef" href="#bib0870">50</a> and the Prochasca–Diclemente test.<a class="elsevierStyleCrossRef" href="#bib0875">51</a> Although other national tests (such as Herrera Carranza<a class="elsevierStyleCrossRef" href="#bib0880">52</a> and Batalla<a class="elsevierStyleCrossRef" href="#bib0885">53</a> tests) have been developed, different method validation studies performed in our country for the assessment of adherence through a clinical interview conclude that these methods are not very useful, showing little consistency with the method of counting tablets. They are a very reliable method if the patient declares himself to be non-compliant, and is therefore very useful to inquire about the reasons for non-adherence.<a class="elsevierStyleCrossRef" href="#bib0890">54</a> These results are consistent with other international studies<a class="elsevierStyleCrossRefs" href="#bib0825">41,42</a> (LE: 2+).In recent years the electronic medical record has been implemented in practically all of our country, and afterwards the electronic prescription, which allows access to the containers that patients withdraw from the pharmacy offices, resulting in a method of easy applicability in clinical practice. It is currently considered as a valid method for the quantification of adherence and allows to explore the dosage from the beginning of the prescription and confirm the persistence in adherence over time. Poor adherence may be detected as a result of intermittent drop-outs in dosing and usually underestimated by other methods. However, these non-compliances can be clinically acknowledged in the event of intermittent failures in treatment efficacy<a class="elsevierStyleCrossRef" href="#bib0895">55</a> (LE: 4).Another indirect method to assess adherence, frequently used in clinical practice but with fewer comparative studies, is assessing the therapeutic effect of the prescribed drugs (and also its known and expected side effects), such as modifications in heart rate, blood pressure (BP), blood glucose, body weight, etc., as well as attendance at scheduled control visits (LE: 4).To date, the methods described are the most commonly used in clinical practice for the assessment of therapeutic adherence. None of them are considered ideal since all have advantages and disadvantages. Combining various methods can significantly increase the validity of the results<a class="elsevierStyleCrossRefs" href="#bib0895">55,56</a> (LE: 4). <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows recommendations on the existing actions to measure therapeutic adherence.Actions to optimize adherence to therapyBearing in mind the positive effect of adherence to placebo, proven even in clinical variables,<a class="elsevierStyleCrossRef" href="#bib0665">9</a> patient adherence is more than just a single drug intake. Therefore, intervention strategies aimed at improving adherence should include aspects other than the drugs involved. The improvement and persistence of adherence to CV drugs is a dynamic process influenced by many factors. One of them is that multiple interventions of reinforcement are required systematically over time.<a class="elsevierStyleCrossRef" href="#bib0895">55</a>The strategies evaluated to improve adherence mainly include behavioral interventions, information to patients, use of fixed-dose combination therapies to reduce the number of daily tablets required and combined strategies. Some of these intervention strategies have been proven effective in improving adherence and/or persistence in the CVD field. Since there is evidence that pharmacological adherence decreases significantly during the first 6 months after prescription,<a class="elsevierStyleCrossRefs" href="#bib0655">7,13</a> these months are a critical and decisive time to act on this problem.Other strategies are aimed at achieving persistence in adherence to therapy. These strategies include mailing video programs or newsletters providing information, multimedia educational programs, review of medications with the patient, follow-up with phone contacts or videophone, “pillbox with Alarm” warning of the time to take medication, etc. In general, complex interventions have provided moderate improvements and simple interventions have shown little or no effect. And all of them have shown a pattern of loss of efficacy through time, requiring reinforcement strategies.<a class="elsevierStyleCrossRefs" href="#bib0895">55,57</a> Numerous interventions to improve adherence in chronic CV disease have been shown to be effective, such as reducing copayment, automated reminders, mail-orders to pharmacies, health care counseling, and fixed-dose combination therapy<a class="elsevierStyleCrossRef" href="#bib0770">30</a> (LE: 1+).A review of the literature identified numerous intervention studies to improve adherence to CV drugs in patients with hypertension, dyslipidemia, congestive heart failure or coronary disease in the community setting. These studies were based on providing information-education, in behavioral programs, social intervention and combined interventions. Behavioral interventions have been shown to be most effective (compared to other types of interventions), whereas adding information strategies has not led to further improvements in adherence<a class="elsevierStyleCrossRef" href="#bib0910">58</a> (LE: 1+).A new strategy to improve drug adherence and health outcomes is the use of management services (electronic or otherwise) of therapeutic drug plans by pharmacists or other health care providers. Several studies have shown significant improvements in adherence to CV drugs. However, interventions in treatment management require a complex approach involving a patient-focused approach, reinforcement interventions and multidisciplinary participation<a class="elsevierStyleCrossRefs" href="#bib0905">57,59,60</a> (LE: 1+).The most current and most frequently used interventions in routine clinical practice to improve patient adherence are focused primarily on correcting the amount of daily tablets.<a class="elsevierStyleCrossRefs" href="#bib0665">9,61</a> Simplifying the dosing schedule is perhaps the intervention with greater effectiveness evidence. There are many evidences showing a direct association between the complexity of the prescribed treatment (in terms of dosage, route of administration, number of drugs, etc.) and adherence. A systematic review of 20 randomized clinical trials concludes that reducing the dosing frequency in patients with chronic diseases improves therapeutic adherence<a class="elsevierStyleCrossRef" href="#bib0930">62</a> (LE: 1+).In this context of simplifying therapeutic regimens, fixed-dose combination therapies are a complementary strategy to improve adherence in many types of diseases. In addition, it reduces production and distribution costs and improves the affordability of treatment.<a class="elsevierStyleCrossRef" href="#bib0655">7</a> In addition, patients included in studies involving a fixed-dose combination therapy show a favorable perception toward said therapy<a class="elsevierStyleCrossRef" href="#bib0935">63</a> (LE: 2+). Therefore, it can be stated that simplifying treatment is an effective strategy, since most studies have found significant improvements in the adherence rate and in the process control in the group of patients where the therapeutic schedule for CV prevention was simplified/facilitated<a class="elsevierStyleCrossRef" href="#bib0940">64</a> (NS: 1+). <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the recommendations regarding actions to be taken to optimize therapeutic adherence.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Fixed-dose combination therapies improve therapeutic adherenceSeveral studies have shown that not all patients receive the appropriate drugs for secondary prevention of CVD. In addition, as mentioned above, a higher number of daily doses and tablets is associated with lower compliance. The effect of fixed-dose combinations on a single tablet on the improvement in therapeutic adherence has been studied in different contexts and <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> summarizes the main studies:<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>As reported in the results of several studies shown in the table above, it has been proven that fixed-dose combination therapies improve therapeutic adherence with respect to free treatments. Simplifying administration and reducing the number of drugs contribute to therapeutic adherence.<a class="elsevierStyleCrossRefs" href="#bib0945">65–67</a> In addition, the potential value of applying the concept of fixed-dose combination therapy for secondary prevention of CVD has been acknowledged by different panels of experts (World Health Organization and Combination Pharmacotherapy and Public Health Research Working Group). In summary, the use of fixed-dose combination therapy simplifies the onset and maintenance of treatment in patients in secondary prevention and in high CVR. In addition, replacing the drugs indicated for secondary or primary prevention of CVD in patients with high CVR by a single daily dose combination improves the therapeutic adherence, the availability and the efficiency of the preventive treatment. <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a> lists the recommendations on these determinants.<elsevierMultimedia ident="tbl0030"></elsevierMultimedia>Expected benefits in Polypill patientsIn patients with no or little adherence to therapy, in secondary cardiovascular preventionThe reduction of CV episodes with ASA, ramipril and statins has been proven in the medical literature and, in addition, it is known that the prognostic relevance of the 3 drugs together is higher than that of each drug separately.<a class="elsevierStyleCrossRef" href="#bib0960">68</a> As we have seen previously, reducing the number of drugs might help increase compliance, which would lead to improved prognosis for patients with poor compliance. There have been some studies on primary and secondary prevention of CVD in terms of the usefulness of fixed-dose combination therapies, although none of them have been carried out with the 3 ingredients of the Polypill. Some of these studies are limited in the sample studied and others are still in the data collection and follow-up phase. Therefore, the results are also limited.<a class="elsevierStyleCrossRef" href="#bib0690">14</a>Some investigations with fixed-dose combination therapies have shown improvements in systolic BP, number of vascular episodes and total mortality in individuals taking these treatments<a class="elsevierStyleCrossRefs" href="#bib0965">69–72</a> (LE: 1++). In the UMPIRE study, mild but statistically significant improvements occurred in systolic BP and LDL-C in patients with fixed-dose combination therapies compared to routine treatment.<a class="elsevierStyleCrossRef" href="#bib0985">73</a> It is estimated that, in the United States alone, the use of a fixed-dose combination therapy with the active ingredients commonly used and with proven effectiveness in individual formulations can prevent 3.2 million CV episodes and 1.7 million strokes.<a class="elsevierStyleCrossRef" href="#bib0990">74</a> However, these effects on reducing CV episodes have recently been questioned in a systematic Cochrane review that grouped studies on primary and secondary prevention of CVD. In this review no benefit was shown for fixed-dose combination therapies for the prevention of CV events. However, a great heterogeneity was observed in the results, not explained by the fact of mixing studies on primary and secondary prevention of CVD. In the same study, BP and lipid parameters dropped more in the group of fixed-dose combination therapies, although the results were also very heterogeneous<a class="elsevierStyleCrossRef" href="#bib0965">69</a> (LE: 1++).A cost-effectiveness study has recently been published with Spanish data comparing the use of the CV Polypill versus its ingredients separately. The results, based on an increased therapeutic adherence and, therefore, higher effectiveness in the real world, show that the treatment with CV Polypill would additionally prevent from 46 non-lethal CV episodes (including 17.48 acute coronary syndromes, 19.62 revascularizations, 6.99 strokes) and 11 lethal cases per 1000 treated patients. In addition, a strategy that includes Polypill is a dominant strategy (higher effectiveness and lower cost than the use of the ingredients separately).<a class="elsevierStyleCrossRef" href="#bib0995">75</a>Polypill, which contains drugs of proven prognostic efficacy, can improve adherence, becoming an interesting CV prevention strategy. In addition, it has been developed in a very specific conceptual framework to improve adherence, accessibility, effectiveness, and therefore cost-effectiveness, and has been tested in clinical studies.<a class="elsevierStyleCrossRef" href="#bib0695">15</a>In summary, simplifying the therapeutic regimen is accompanied by best results in terms of therapeutic adherence and best control of CVR factors, both in primary and secondary prevention<a class="elsevierStyleCrossRef" href="#bib0690">14</a> (LE: 1+). However, no differences were found in clinical episodes, probably because it was not the purpose of the studies, because of the limited sample size of the studies and the low number of episodes<a class="elsevierStyleCrossRef" href="#bib0690">14</a>(LE: 1++).In adherent patients on secondary prevention of cardiovascular diseaseRecently the European guidelines for the prevention of CVD in clinical practice has been published<a class="elsevierStyleCrossRef" href="#bib1000">76</a> which includes the recommendation of using Polypill to improve adherence. Additionally, this guidelines also makes hygiene and dietary recommendations and usually includes a section where it is recommended that the patient know and understand their treatment. As in the case of non-adherent or poorly adherent patients, “the advantage that can be expected from a fixed-dose combination therapy is the simplification of the therapeutic regimen, particularly in polypharmacy patients and with comprehension difficulties”. Specifically, in the group of patients with good therapeutic adherence, fixed-dose combination therapy simplifies treatment and may encourage long-term adherence.Identifying clinical situations in cardiovascular secondary prevention tributary of the administration of PolypillFor all of the above mentioned, Polypill can be very useful in certain contexts to promote therapeutic adherence. Clinical situations in CV secondary prevention have been reported where administration of Polypill would bring benefits and include patients with coronary events (acute, chronic, and revascularized or not), patients with ischemic stroke, and patients with symptomatic peripheral artery disease.The clinical criteria that might determine the indication of Polypill in secondary prevention of CVD, would be patients with a history of non-adherence or with some of the predictors of pharmacological non-adherence; Patients controlled with the individual drugs; Patients with poor control with equipotent doses and with adherence problems and, finally, patients with multiple diseases and polypharmacy patients.Timing for prescribing PolypillAlthough there are no studies that have addressed the optimal time to start treatment with Polypill, experts agree that the following should be evaluated: combination therapy at the acute stage of the ischemic event; if difficulties are predicted on patient adherence, on accessibility to treatment or on follow-up.The therapeutic purposes for secondary prevention of CVD in patients with confirmed coronary disease are well described in the clinical practice guidelines of all scientific societies. These therapeutic purposes include healthy lifestyle habits in both physical exercise and eating habits, as well as the control of CVR factors with BP levels <140/90mmHg, and LDL-c <70mg/DL (1.8mmol/l) or a ≥50% reduction in baseline LDL-c levels. It is important to emphasize that these therapeutic purposes must be maintained throughout the patient's life.<a class="elsevierStyleCrossRefs" href="#bib1005">77–80</a>In patients who are already being treated with the different drugs separately, replacing triple therapy by Polypill would improve patient adherence and might be used as a strategy to improve control of CVR factors and therefore decrease vascular episodes.<a class="elsevierStyleCrossRefs" href="#bib1025">81,82</a>Because of these circumstances, and in the specific case of Polypill, the main determinants to replace an individualized therapy by Polypill are mainly the non-compliance of the subject, the difficulty of access to treatments, polypharmacy or the economic advantages that this might imply. In all cases, it should be guaranteed (as far as possible) that the therapeutic response for proper levels of LDL-c and BP be obtained with Polypill. Otherwise, we should evaluate the possibility of separately adding the necessary extra dose of complementary medication or return to the individualized treatment. But, previously it should be verified that not complying with the purposes is not due to non-compliance with the treatment with Polypill, since it might worsen as the number of drugs increases. <a class="elsevierStyleCrossRef" href="#tbl0035">Table 7</a> lists the recommendations on the timing to prescribe Polypill and replacement to Polypill and vice versa.<elsevierMultimedia ident="tbl0035"></elsevierMultimedia>Clinical situations where Polypill would not be indicatedOf the 3 ingredients used in Polypill, atorvastatin is offered in a single 20mg dose. Such a dose might be adequate but, in a number of patients, it may not have the therapeutic potency to obtain the therapeutic goals indicated in the clinical practice guidelines. Ramipril is the only Polypill ingredient that allows a titration according to the patient's requirements as it is offered in 3 different doses (2.5, 5 and 10mg). But, like atorvastatin it may not have the power necessary to comply with the therapeutic purposes in patients with difficult HT control. On the other hand, each ingredient of Polypill (ASA 100mg, atorvastatin 20mg and ramipril at 3 different doses) might cause side effects and specific contraindications, although the adverse effects of each ingredient manifest clinically differently and might be identified relatively easily.Although we can state that Polypill offers proven effectiveness and greater adherence to therapy there are 2 scenarios in which its administration would not be indicated. These situations are defined in patients where treatment with Polypill does not obtain the therapeutic purposes indicated by the guidelines of clinical practice or at least an acceptable approach to those objectives and in those patients with adverse effects to one of the 3 ingredient of Polypill (LE: √, based on expert opinion with 83% agreement).Specific clinical situations that may benefit from PolypillProfile of high or very high risk patients with subclinical cardiovascular diseaseCVD is a continuum ranging from the presence of risk factors in isolation to disease clinically reported (including the acute episode), from subclinical disease or asymptomatic lesion of the target organs. The presence of subclinical CVD, defined as the presence of organ damage, left ventricular hypertrophy, kidney failure, microalbuminuria/proteinuria, increased media intima thickness, atherosclerotic plaque, lower ankle-brachial index, etc. places patients at a high or very high CVR level. This makes them, in most cases, candidates for a pharmacological intervention, not only for the control of their risk factors but also for organ protection, not being enough the treatment aimed at modifying the lifestyle.Blockade of the renin–angiotensin–aldosterone system is one of the interventions that have been proven beneficial in these patients.<a class="elsevierStyleCrossRef" href="#bib1035">83</a> Both ACEI and ARBs have demonstrated, in addition to lowering BP, the ability to provide organic protection at vascular, cardiac and kidney levels.<a class="elsevierStyleCrossRefs" href="#bib1040">84–86</a> Several ACE inhibitors (enalapril, lisinopril, quinapril, ramipril and trandolapril) and ARBs (candesartan, valsartan and losartan) are indicated in patients with left ventricular dysfunction or clinical heart failure.<a class="elsevierStyleCrossRef" href="#bib1035">83</a> However, only telmisartan and ramipril are indicated to reduce CVR based on clinical trials.<a class="elsevierStyleCrossRef" href="#bib1035">83</a> Ramipril is indicated in CV prevention to reduce CV morbidity and mortality in patients with proven atherothrombotic disease or diabetes with at least one RCV factor<a class="elsevierStyleCrossRef" href="#bib1035">83</a> (LE: 4).Statins are also drugs that have been shown to provide organic protection in patients with high CVR in primary prevention of CVD.<a class="elsevierStyleCrossRefs" href="#bib1055">87–93</a> (LE: 1++). The benefit of antiaggregation, however, is controversial in primary prevention. Therefore, it should be individualized in every case, depending on the expected risk/benefit. While in secondary prevention their benefit is proven, in primary prevention they may only be recommended in patients with high CVR and low risk of hemorrhage.<a class="elsevierStyleCrossRefs" href="#bib1090">94–96</a> (LE: 1++).Despite the CVR of patients with subclinical CVD, the asymptomatic nature of their disease and the lack of a previous CV episode have an influence on the poor compliance and lack of adherence to the prescribed treatment. Therefore, many of these patients may benefit from a therapeutic strategy that facilitates compliance such as fixed-dose combination therapy, consisting of those pharmacological ingredients that have been proven beneficial in the presence of subclinical CV disease.As previously discussed, the use of a fixed-dose combination therapy may reduce CV morbidity and mortality<a class="elsevierStyleCrossRef" href="#bib0965">69</a> (LE: 1++) and although there is no definitive evidence of the ingredients that should be part of these treatments, there is consensus that they should include a renin–angiotensin–aldosterone system blocker and a statin<a class="elsevierStyleCrossRef" href="#bib0965">69</a> (LE: 1++). In addition, 2 systematic reviews/meta-analyzes have been proven to have an effect on CV protection, combining ASA with statins.<a class="elsevierStyleCrossRefs" href="#bib1105">97,98</a> (LE: 1+). <a class="elsevierStyleCrossRef" href="#tbl0040">Table 8</a> lists the recommendations in this subtype of patients.<elsevierMultimedia ident="tbl0040"></elsevierMultimedia>Profile of high or very high risk patients without established or subclinical cardiovascular diseasePrimary prevention of CVD is aimed at preventing from CV episodes in patients without CVD symptomatology. In patients with a high CVR, clinical practice guidelines recommend the use of statins and antihypertensive drugs to reduce this CVR and vascular accidents.<a class="elsevierStyleCrossRefs" href="#bib1015">79,99,100</a> In the case of ASA, the third ingredient of the Polypill, the controversy over its benefit in primary prevention of CVD is more significant due to the lack of clear evidence of a favorable benefit/risk ratio in these patients. Nevertheless, some publications mention that in patients with high CVR, the clinical benefit might be obtained when the absolute risk is reduced above the risk of hemorrhage.<a class="elsevierStyleCrossRef" href="#bib1125">101</a>There is some evidence on the effectiveness and safety of the use of fixed-dose combination therapies in patients with primary prevention of CVD.<a class="elsevierStyleCrossRefs" href="#bib0975">71,102–104</a> However, the lack of specific evidence in the case of Polypill caused a debate among the group of experts due to the controversial use of ASA in these patients. This is why the panel of experts did not reach consensus on the possibility of recommending Polypill in all patients on primary prevention of CVD, being exclusively recommended in certain patients with very high RCV (see previous section).Replacement of an angiotensin II receptor blocker by the Polypill angiotensin converting enzyme inhibitorThere are different pharmacological groups capable of blocking the renin–angiotensin–aldosterone system, with ACEIs and ARBs being the main ones. As previously mentioned, both ACEIs and ARBs have been proven capable of providing organic protection at vascular, cardiac and kidney levels, in addition to lowering BP<a class="elsevierStyleCrossRefs" href="#bib1040">84–86</a> (LE: 4).Although its mechanism of action is different, its effectiveness and safety are similar from a CV point of view. These two pharmacological groups are mainly different because of the best tolerability of ARBs, mainly due to the lower incidence of cough, a side effect that occurs in less than 10% of those treated with ACE inhibitors and which is related to its effect on bradykinins.The effect of ARBs on the risk of myocardial infarction has been analyzed in a meta-analysis of 20 clinical trials involving a total 109,000 patients, been proved to have the same capacity as ACE inhibitors to reduce the risk of Myocardial infarction (OR: 1.008, CI 95%: 0.926–1.099)<a class="elsevierStyleCrossRef" href="#bib1145">105</a> (LE: 1++). Direct comparisons, such as in the ONTARGET<a class="elsevierStyleCrossRef" href="#bib1150">106</a> trial, in patients with high CVR do not find differences between ACE inhibitors and ARBs in their protective effect on CV morbidity and mortality. In this study, telmisartan and ramipril were equivalent in their protective effect on CV episodes (LE: 1+). Based on this, the European Hypertension Guidelines concluded in 2007 that both pharmacological groups were interchangeable from a point of view of CV protection<a class="elsevierStyleCrossRefs" href="#bib1010">78,85</a> (LE: 4).In summary, there is sufficient evidence based on clinical trials showing that there are no differences in the organic protection provided by ACE inhibitors and ARBs. The main difference is in the higher incidence of cough with ACE inhibitors (see recommendations in <a class="elsevierStyleCrossRef" href="#tbl0045">Table 9</a>).<elsevierMultimedia ident="tbl0045"></elsevierMultimedia>Replacement between statinsStatins are useful in secondary prevention of CVD and in the control of LDL-C levels and are recommended by clinical practice guidelines<a class="elsevierStyleCrossRefs" href="#bib1015">79,80</a> (LE: 1++). Specifically, atorvastatin 20mg, with a hypocholesterolemic potency reducing LDL-C by 41–43%<a class="elsevierStyleCrossRefs" href="#bib1155">107,108</a> is the most used statin, with a proper balance between efficacy and adverse effects<a class="elsevierStyleCrossRef" href="#bib1165">109</a> (LE: 1++).In high CVR situations (secondary prevention of CVD, diabetes mellitus with other risk factors or target organ damage, high risk primary prevention of CVD), statin therapies always require potent high dose statins to try to achieve C-LDL reduction purposes<a class="elsevierStyleCrossRefs" href="#bib1015">79,110</a> (LE: 4).In patients in secondary prevention of CVD, statin doses may be reduced in up to 42% patients due to adverse effects or safety reasons. These decreases in the dose of statins cause a reduction of the hypocholesterolemic effect, and may be accompanied by increased CVR<a class="elsevierStyleCrossRefs" href="#bib1175">111,112</a> (LE: 2+) (see recommendations in <a class="elsevierStyleCrossRef" href="#tbl0045">Table 9</a>).Polypill limitations, precautions and contraindicationsIn the context of any chronic pharmacological treatment it is important to consider the disadvantages and risks of administering fixed-dose drugs by means of Polypill. What happens if we do not comply with the therapeutic purposes indicated in the clinical guidelines, both in very high-risk patients and patients after an ischemic episode? What should we do if the patient begins to have side effects to any ingredient of the Polypill (e.g. gastrointestinal side effects caused by ASA, cough caused by ACEI, and myopathies or enzyme elevation for statins, etc.)? Can the occurrence of side effects make the patient stop taking the medication and lose the hypothetical benefit of all the pharmacological ingredients of Polypill? Can the combination of several drugs and their excipients cause adverse effects other than each drug individually?Although there are currently no publications on the adverse effects of Polypill, the Cochrane systematic review conducted to evaluate other fixed-dose combination therapies for CV prevention<a class="elsevierStyleCrossRef" href="#bib0965">69</a> showed that (LE: 1++), the reduction in BP and lipid parameters is higher than expected. In addition, the use of fixed-dose combination therapies is associated with mild increases in the frequency of side effects (30%), compared to placebo or with the use of drugs administered individually, which are mostly not serious, mainly because there are more patients taking the medication. Approximately half of the patients with side effects treated with fixed-dose combination therapies discontinue their use. Treatment discontinuation in fixed-dose combination therapies is 14 vs 11% in individuals treated with placebo (RR: 1.26, CI 95%: 1.02–1.55). Finally, the increase in the therapeutic adherence to fixed-dose combination therapy is associated to the benefit in complying with the therapeutic purposes, and explains the increased incidence of side effects.Therefore, the panel of experts concludes that: The disadvantages and risks of administering fixed doses by means of Polypill are to not comply with the required or optimal control purposes. However, the use of fixed-dose combination therapies is associated with a higher reduction in BP and lipid values than expected, due to the increased therapeutic adherence. In addition, there is insufficient data to determine the frequency of adverse effects for Polypill, as compared to the 3 drugs separately. However, in other studies, the use of other fixed-dose combination therapies has been associated with mild increase in the frequency of non-serious side effects compared to use of the drugs separately, and this can be attributed to the improved adherence<a class="elsevierStyleCrossRef" href="#bib0965">69</a> (LE: 1++).Regarding the precautions for treatment with Polypill (ASA, ramipril and atorvastatin), the Polypill datasheet, currently available under the name Trinomia®, details the warnings for special populations, the need for monitoring during treatment and warnings about specific adverse reactions.<a class="elsevierStyleCrossRef" href="#bib0740">24</a>Therefore, precautions in the use of the Polypill in CV prevention are specified in its datasheet and arise from the precautions in the use of ASA, ramipril and atorvastatin.In addition, some experts consider it appropriate to emphasize that an increased risk of adverse effects should not be expected as a result of interactions between them and that the patient should understand that simplifying treatment is not synonymous with detracting from it.Skipping one dose is the most frequent cause of unintended therapeutic non-compliance.<a class="elsevierStyleCrossRef" href="#bib1185">113</a> Since the approved dosing regimen for Polypill is the same as that of its 3 ingredients separately,<a class="elsevierStyleCrossRef" href="#bib1190">114</a> the recommendations to be followed are specified in the data sheet since no short-term consequences are anticipated given the half-life of each of them (LE: 1+) (see recommendations in <a class="elsevierStyleCrossRef" href="#tbl0050">Table 10</a>).<elsevierMultimedia ident="tbl0050"></elsevierMultimedia>Habits and behaviors of the patient under treatment with PolypillEven though the patient follows an adequate therapeutic regimen, there remains a residual risk of a similar magnitude, or higher, compared to the risk that has been eliminated, due in part to the genetic load and unsuitable lifestyles. Therefore drugs, in our case Polypill, should be associated with lifestyle habits and behaviors that contribute to reduce residual risk and limit the gene expression leading to the progression of the disease and/or to developing new acute processes. Therefore, patients treated pharmacologically in both primary and secondary prevention of CVD require lifestyle heart-healthy habits, including<a class="elsevierStyleCrossRef" href="#bib1195">115</a> quitting smoking and other toxic substances such as cocaine, in addition to inadequate alcohol consumption (LE: 1+, B), following a heaart-healthy diet (LE: 1++, DR: A), practice regular moderate physical exercise, 2h 30min a week or 75min of intense aerobic exercise (LE: 1+, DR: B), normal body weight with a BMI ranging from 18 to 25kg/m2 (LE: 1+, DR: B). Finally, following cardiac training and rehabilitation programs that favor physical activity and heart-healthy lifestyle habits are extremely useful tools that have also been shown to be effective in adherence to pharmacological treatment (LE: 2++, DR: B) (see recommendations in <a class="elsevierStyleCrossRef" href="#tbl0055">Table 11</a>).<elsevierMultimedia ident="tbl0055"></elsevierMultimedia>The use of drugs proven efficient in secondary prevention of CVD has been increased. However, poor adherence to healthy lifestyles, and the fact that it does not improve through the years, is disappointing, as evidenced by the EUROASPIRE I, II and III European records and even with clear worsening in EUROASPIRE IV.<a class="elsevierStyleCrossRefs" href="#bib0955">67,116,117</a> This last record emphasizes that in a population of patients, 6 months after an acute coronary syndrome, or requiring percutaneous or surgical coronary revascularization,<a class="elsevierStyleCrossRef" href="#bib0955">67</a> there is persistent smoking in 16%, little or no physical exercise in 59.9%, 37.6% are obese (BMI≥30kg/m2) and 58.2% have central obesity (waist circumference ≥102cm in men or ≥88cm in women). 42.7% had BP ≥140/90mmHg (≥140/80 in diabetics). 80.5% have LDL-c ≥70mg/dl (≥1.8mmol/l). 26.8% had diabetes mellitus.FundingFerrer Laboratories have funded the logistics necessary for drafting this paper, but in no case have they participated in the debates or decisions.Conflict of interestsThe authors report no conflict of interest.Guarantees of scientific societiesSpanish Society of Cardiology (SEC).Spanish Society of Internal Medicine (SEMI).Spanish Society of Family and Community Medicine (SemFYC).Spanish Society of General and Family Practitioners (SEMG).Spanish Society of Primary Care Physicians (SEMERGEN)." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres813170" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec810532" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres813171" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec810531" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Cardiovascular disease" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Concept of adherence to therapy" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Polypill" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Purpose of the consensus document and field of application" ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "Methodology used in the document" ] ] ] 5 => array:3 [ "identificador" => "sec0035" "titulo" => "Recommendations" "secciones" => array:12 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Impact of lack of adherence on cardiovascular health" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Adherence to therapy in secondary prevention and in patients of high, or very high risk with subclinical cardiovascular disease" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Actions to measure adherence to therapy" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Actions to optimize adherence to therapy" ] 4 => array:2 [ "identificador" => "sec0060" "titulo" => "Fixed-dose combination therapies improve therapeutic adherence" ] 5 => array:3 [ "identificador" => "sec0065" "titulo" => "Expected benefits in Polypill patients" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "In patients with no or little adherence to therapy, in secondary cardiovascular prevention" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "In adherent patients on secondary prevention of cardiovascular disease" ] ] ] 6 => array:2 [ "identificador" => "sec0080" "titulo" => "Identifying clinical situations in cardiovascular secondary prevention tributary of the administration of Polypill" ] 7 => array:2 [ "identificador" => "sec0085" "titulo" => "Timing for prescribing Polypill" ] 8 => array:2 [ "identificador" => "sec0090" "titulo" => "Clinical situations where Polypill would not be indicated" ] 9 => array:3 [ "identificador" => "sec0095" "titulo" => "Specific clinical situations that may benefit from Polypill" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0100" "titulo" => "Profile of high or very high risk patients with subclinical cardiovascular disease" ] 1 => array:2 [ "identificador" => "sec0105" "titulo" => "Profile of high or very high risk patients without established or subclinical cardiovascular disease" ] 2 => array:2 [ "identificador" => "sec0110" "titulo" => "Replacement of an angiotensin II receptor blocker by the Polypill angiotensin converting enzyme inhibitor" ] 3 => array:2 [ "identificador" => "sec0115" "titulo" => "Replacement between statins" ] ] ] 10 => array:2 [ "identificador" => "sec0120" "titulo" => "Polypill limitations, precautions and contraindications" ] 11 => array:2 [ "identificador" => "sec0125" "titulo" => "Habits and behaviors of the patient under treatment with Polypill" ] ] ] 6 => array:2 [ "identificador" => "sec0130" "titulo" => "Funding" ] 7 => array:2 [ "identificador" => "sec0135" "titulo" => "Conflict of interests" ] 8 => array:2 [ "identificador" => "sec0140" "titulo" => "Guarantees of scientific societies" ] 9 => array:2 [ "identificador" => "xack272671" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-09-14" "fechaAceptado" => "2016-10-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec810532" "palabras" => array:6 [ 0 => "Cardiovascular disease" 1 => "Prevention" 2 => "Adherence" 3 => "Recommendations" 4 => "Combination therapy" 5 => "Polypill" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec810531" "palabras" => array:6 [ 0 => "Enfermedad cardiovascular" 1 => "Prevención" 2 => "Adherencia" 3 => "Recomendaciones" 4 => "Tratamiento combinado" 5 => "Polypill" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Cardiovascular disease is a chronic disorder which is usually already at an advanced stage when the first symptoms develop. The fact that the initial clinical presentation can be lethal or highly incapacitating emphasizes the need for primary and secondary prevention. It is estimated that the ratio of patients with good adherence to secondary prevention of cardiovascular disease is low and also decreases gradually over time. The Polypill for secondary prevention of cardiovascular disease is the first fixed-dose combination therapy of salicylic acid, atorvastatin and ramipril approved in Spain. The purpose of this consensus document was to define and recommend, through the evidence available in the literature and clinical expert opinion, the impact of treatment adherence in the secondary prevention of cardiovascular disease and the use of the Polypill in daily clinical practice as part of a global strategy including adjustments in patient lifestyle. A RAND/UCLA methodology based on scientific evidence, as well as the collective judgment and clinical expertise of an expert panel was used for this assessment. As a result, a final report of recommendations on the impact of the lack of adherence to treatment of secondary prevention of cardiovascular disease and the effect of using a Polypill in adherence of patients was produced. The recommendations included in this document have been addressed to all those specialists, cardiologists, internists and primary care physicians with competence in prescribing and monitoring patients with high and very high cardiovascular risks." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La enfermedad cardiovascular suele estar en fase avanzada cuando aparecen los primeros síntomas. El hecho de que la presentación clínica inicial pueda ser letal o altamente incapacitante enfatiza la necesidad de la prevención primaria y secundaria. Se estima que la proporción de pacientes con buena adherencia en prevención secundaria de la enfermedad cardiovascular es baja y disminuye progresivamente en el tiempo. La Polypill para la prevención cardiovascular secundaria es el primer tratamiento combinado en dosis fija de ácido acetilsalicílico, atorvastatina y ramipril aprobada en España. El propósito de este documento de consenso fue definir y recomendar, a través de la evidencia en la literatura y la opinión clínica de expertos, el impacto de la adherencia al tratamiento de prevención cardiovascular secundaria y el uso en la práctica clínica de la Polypill integrado en una estrategia global que incluye modificaciones en el estilo de vida. Para la realización de este consenso se ha utilizado la metodología RAND/UCLA que está basada en la evidencia científica y en el juicio colectivo y experiencia clínica de un panel de expertos. Como resultado se ha elaborado un informe final de recomendaciones sobre el impacto de la falta de adherencia al tratamiento de la prevención cardiovascular secundaria y el efecto del uso de una Polypill en la adherencia terapéutica de los pacientes. Las recomendaciones de este documento se orientan a todos aquellos especialistas, cardiólogos, médicos internistas y médicos de atención primaria con competencia en la prescripción y seguimiento de los pacientes de alto y muy alto riesgo cardiovascular y que requieran prevención secundaria." ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: González-Juanatey JR, Mostaza JM, Lobos JM, Abarca B, Llisterri JL, Baron-Esquivias G, et al. Documento de consenso del uso clínico de la Polypill en la prevención secundaria del riesgo cardiovascular. Med Clin (Barc). 2017;148:139.e1–139.e15." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "The authors state that they have contributed to the critical revision of the intellectual content, the development of the consensus document, the preparation of the article and the approval of this final version." ] ] "multimedia" => array:11 [ 0 => array:9 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Scottish Intercollegiate Guidelines Network.<a class="elsevierStyleCrossRef" href="#bib0750">26</a>" "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Levels of scientific evidence</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High quality meta-analysis, systematic reviews of clinical trials or high-quality clinical trials with very little risk of bias \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Well-conducted meta-analysis, systematic reviews of clinical trials or well-conducted clinical trials with low risk of bias \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1− \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Meta-analysis, systematic reviews of clinical trials or clinical trials with high risk of bias \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High quality systematic reviews of cohort or case-control studies. Cohort or case-control studies with very low risk of bias and moderate probability of causal relationship \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Well-conducted cohort or case-control studies with low risk of bias and moderate probability of causal relationship \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2− \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cohort or case-control studies with high risk of bias and significant risk of no causal relationship \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Non-analytical studies such as case reports and case series \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Expert Reviews \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Degrees of recommendation</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">At least one meta-analysis, systematic review or clinical trial classified as 1+ and directly applicable to the target population of the guideline; Or a number of scientific evidence consisting of studies classified as 1+ and very consistent with each other \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A number of scientific evidence consisting of studies classified as 2++, directly applicable to the target population of the guideline and very consistent with each other; Or scientific evidence extrapolated from studies classified as 1++ or 1+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A number of scientific evidence consisting of studies classified as 2++, directly applicable to the target population of the guideline and very consistent with each other; Or scientific evidence extrapolated from studies classified as 2++ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Scientific evidence of level 3 or 4; or scientific evidence extrapolated fromstudies rated as 2+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Good clinical practice</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recommended practice, based on clinical experience and consensus by panel of experts \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365565.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Levels of evidence and degrees of recommendation (SIGN)." ] ] 1 => array:9 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Oxford Center for Evidence-Based Medicine.<a class="elsevierStyleCrossRef" href="#bib0755">27</a>" "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Levels of scientific evidence</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systematic review with homogeneity of level 1 studies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ib \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Level 1 studies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Level 2 studies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systematic review of level 2 studies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Level 3 studies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systematic review of level 3 studies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Consensus, opinions from panel of experts with no explicit critical assessment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Level 1 studies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">They meet: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– Masked comparison with a valid reference test (“gold standard”) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– Adequate spectrum of patients \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Level 2 studies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">They present only one of these biases: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– Non-representative population (the sample does not reflect the population where the test will be applied) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– Comparison with an inadequate reference standard (“gold standard”) (the test to be evaluated is part of the gold standard or the test result influences the gold standard) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– Non-masked comparison \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– Case-control studies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Level 3 studies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">They present 2 or more of the criteria described in Level 2 studies. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Recommendation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Evidence \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ia or Ib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IV \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365561.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Levels of scientific evidence and recommendations for questions on diagnosis." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "A: agreement% y (n); DR: degree of recommendation; MEMS: Medication Event Monitoring Systems LE: level of evidence." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the determinants of the lack of therapeutic adherence \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A (No.) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE/DR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">There is no “patient with a non-adherence personality”, although there are predictors of non-adherence. Therefore, adherence must be pursued in all patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2++/B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib0655">7,118</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365569.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the actions to measure adherence to therapy \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A (No.) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE/DR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Direct methods to measure adherence are not of choice in routine clinical practice<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">87% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Indirect methods are the most applicable methods in routine clinical practice, keeping in mind that they overestimate the adherence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The opinion or perception of the health professional is not sufficiently valid as a method of measuring adherence<a class="elsevierStyleCrossRef" href="#tblfn0020">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2+/D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib0845">45,46</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Methods of measurement based on clinical interview are most useful in standard practice, although they offer the limitation of poor agreement with other more valid methods (such as pill counts) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">87% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1+/A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib0825">41,42,48–51,54</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The control of prescriptions dispensed in pharmacy, through the electronic prescribing modules of the clinical history, provides acceptable validity and clinical applicability \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4/D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRef" href="#bib0895">55</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Using more than one method of therapeutic adherence assessment provides best reliability at the expense of increasing the time spent with the patient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4/D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib0895">55,56</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The measurement of pharmacological adherence will be initiated through the personalized clinical interview method, using some of the self-questionnaire tests. If the patient states to be compliant, but non-compliance is still suspected, the method of counting tablets will be applied. In cases of monitoring the non-compliance pattern, counting will be performed with MEMS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1+/B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib0825">41,42,48,54</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">When a therapeutic failure occurs, poor therapeutic adherence might be the cause<a class="elsevierStyleCrossRef" href="#tblfn0010">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">87% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4/D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRef" href="#bib0895">55</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365560.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Some experts believed that in some cases direct methods can be useful and provide relevant information. b In the opinion of some experts, the perception of the health professional is not valid as a measure (degree of adherence). However, in some cases it might be a good approach." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "c" "nota" => "Some experts explained that the suspicion should be verified to rule out a poor outcome or poor treatment selection." ] ] ] "descripcion" => array:1 [ "en" => "Recommendations on the determinants of lack of therapeutic adherence and recommendations on the actions to measure adherence." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "A: agreement % y (n); CV: cardiovascular; DR: degree of recommendation; LE: level of evidence." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No. \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A (No.) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE/DR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">10. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No specific intervention can be recommended for all patients. The causes of lack of adherence should be analyzed in each case, which will allow to select the appropriate strategies for each patient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">86% (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">11. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">With the evidence currently available it cannot be stated that a specific intervention to improve adherence is better than another. Combining interventions seems to be the best strategy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">12. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A good professional-patient relationship is crucial<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> and communication should be effective, since these are key elements to facilitate the understanding by the patient of their disease and treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2++/B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRef" href="#bib0655">7</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">13. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The therapeutic plan should be agreed upon with the patient to facilitate their involvement and involve them in their monitoring and follow-up. Self-responsibility should be encouraged and family members should be involved \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1+/B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib0650">6,58</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">14. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Any strategy should include simplification of the therapeutic schedule to improve therapeutic adherence, reducing the number of daily doses and using the fixed-dose combination therapy<a class="elsevierStyleCrossRef" href="#tblfn0020">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1+/Ac \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib0965">69–73,81,82</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">15. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Therapeutic adherence has to be evaluated periodically not making the patient feel guilty \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">16. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Every pharmacological intervention should consider strategies to reinforce adherence over time \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4/D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib0895">55,57</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">17. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Effective and economically affordable drugs should be developed to ensure adherence to the therapeutic regimen in secondary prevention of CVD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2+/C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRef" href="#bib0725">21</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">18. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Specific recommendations should be made specifically for less adherent populations such as: elderly, patients with multivascular disease, cerebrovascular disease, comorbidities, etc. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2+/C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRef" href="#bib0810">38</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365568.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "It includes physicians, nurses and community pharmacists." ] 1 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "b" "nota" => "One expert wanted to clarify that this simplification does not only mean reducing the number of doses and introducing fixed combinations, but it is also important to reduce unnecessary drugs. c Degree of recommendation assigned according to the evidence obtained from the references indicated as source reference, discussed in this and the following section." ] ] ] "descripcion" => array:1 [ "en" => "Recommendations on actions to optimize adherence to therapy." ] ] 4 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ASA: acetylsalicylic acid; CVD: cardiovascular disease; HTA: hypertension; 95% CI: 95% confidence interval; RR: relative risk." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Ref. \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study design \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Results/conclusions \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">US \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#bib0735">23</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Meta-analysis of 68 studies, 4 of them on patients with hypertension • Comparison of treatment in fixed-dose combinations versus conventional pharmacological regimen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Fixed-dose combination therapies decreased the risk of noncompliance by 26% compared to the conventional schedule (combined RR: 0.74, CI 95%: 0.69–0.80; p<0.0001) • Fixed-dose combination therapies for HT decreased the risk of medication failure by 24% compared to the standard regimen (combined RR: 0.76, CI 95%: 0.71–0.81; p<0.0001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#bib0985">73</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Randomized clinical trial UMPIRE • 1002 patients at high risk for CVD • Comparison of fixed-dose combination therapy: ASA, simvastatin, lisinopril and a drug for hypertension (atenolol or hydrochlorothiazide) vs standard clinical care \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• In patients with fixed-dose combination therapy, adherence improved with respect to standard clinical care (86 vs 95). 65%; RR to be adherent: 1.33, CI 95%: 1.26–1.41; p<0.001) • In the subgroup of patients with lower adherence at baseline (n=727), adherence at the end of the study was 77 vs 23% (RR: 3.35, CI 95%: 2.74–4.09; p<0.001 for interaction) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#bib0695">15</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• FOCUS clinical trial with 695 randomized patients • Comparison of a fixed-dose combination therapy (ASA, simvastatin and ramipril) compared to the 3 drugs administered separately • Adherence to treatment measured with Morisky Green and tablet count at 9 months of follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Patients with fixed-dose combination therapy showed better adherence compared to the group receiving the drugs seaparately: 50.8% adherent patients vs 41% (p=0.019; intention to treat population) and 65.7 vs 55.7% (p=0.012; per protocol population) when using the main endpoint (attending the final visit with Morisky Green=20 and high pill count (80–110%). Adherence was also higher in this group when measured by Morisky Green alone (68 vs 59% of adherent patients, p=0.049) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1++ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#bib1215">119</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Randomized clinical trial IMPACT • 513 patients at high risk for CVD • Comparison of fixed-dose combination therapy (ASA, simvastatin, lisinopril and atenolol or hydrochlorothiazide) with conventional pharmacological regimen • Adherence at month 12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Adherence to the 4 recommended drugs was higher within the fixed-dose combination therapy than in patients with conventional drug regimens (81 vs 46% (RR: 1.75, CI 95%: 1.52–2.03; p<0.001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1++ \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365566.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Results of therapeutic adherence in fixed-dose combination therapies." ] ] 5 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at6" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "A: agreement % y (n); CV: cardiovascular; DR: degree of recommendation; LE: level of evidence." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the use of fixed-dose combination therapies \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A (No.) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE/DR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">19. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A fixed-dose combination containing the active ingredients that have demonstrated its benefits in CV prevention can improve prevention by increasing patient adherence to treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4/D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib0695">15,23,65–67,119</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">20. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fixed-dose combination therapies improve therapeutic adherence mainly in secondary prevention of CVD and particularly in patients such as: young, elderly, patients with depression, patients with low economic resources, who live in an urban area or who have suffered a stroke \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1++/A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib0655">7,15</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365562.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Recommendations on the use of fixed-dose combination therapies." ] ] 6 => array:8 [ "identificador" => "tbl0035" "etiqueta" => "Table 7" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at7" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "A: agreement% y (n); DR: degree of recommendation; LE: level of evidence." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="middle" scope="col" style="border-bottom: 2px solid black">Nr \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="middle" scope="col" style="border-bottom: 2px solid black">Recommendations on the timing of Polypill prescription \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="middle" scope="col" style="border-bottom: 2px solid black">A (No.) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="middle" scope="col" style="border-bottom: 2px solid black">LE/DR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">21. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Although the Polypill does not include high doses of statins and these are recommended generically after an acute episode, the onset with Polypill can be evaluated at hospital admission by an acute CV event if there are predicted difficulties in the patient's adhesion, in accessibility to therapy or follow-up. If prescription takes place when the patient is admitted or discharged, it will depend on every hospital and the hospital's possibilities<a class="elsevierStyleCrossRef" href="#tblfn0025">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="top">92% (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">22. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A key timing to assess Polypill prescription is when low adherence to treatment is detected for any reason, during the follow-up of a patient already distant from the acute CV episode. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">23. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Another time to assess Polypill prescription is in polypharmacy patients or patients claiming reduction/simplification of their multiple treatments, regardless of being or not an adherent patient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">24. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In case of a patient in secondary prevention of CVD, their individual treatment can be modified (one, 2 or 3 medications separately) to Polypill as a therapeutic alternative: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(A) When low therapeutic adherence or difficulty to access drugs by any circumstance is detected \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(B) When polymerization needs to be reduced specifically with the express claim of the patient in this regard and particularly in the adherent patient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">25. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In a patient treated with Polypill, therapy should be modified to a separate and individualized treatment: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• When the therapeutic purposes of the guidelines have not been met, having discarded that it is the consequence of a therapeutic noncompliance. The possibility of adding the extra necessary dose of other drugs separately might be considered to meet the purposes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• When intolerance to any Polypill ingredients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• When any contraindication to any Polypill ingredients occurs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365567.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "a" "nota" => "The experts considered it important that the hospital discharge report should indicate whether the patient is provided with Polypill, at the dose that the cardiologist considers necessary, regardless of being or not compliant." ] ] ] "descripcion" => array:1 [ "en" => "Recommendations on the timing of Polypill prescription." ] ] 7 => array:8 [ "identificador" => "tbl0040" "etiqueta" => "Table 8" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at8" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "A: agreement % y (n); CVD: cardiovascular disease; IMT: average intima thickness; DR: degree of recommendation; LVH: left ventricular hypertrophy; ABI: ankle-brachial index; LE: level of evidence." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No. \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the benefits of Polypill in patients with high or very high CVR with subclinical cardiovascular disease \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A (No.) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE/DR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">26. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">There is sufficient evidence to consider the use of Polypill in the following subgroups of patients for subclinical CVD, as long as they do not present a high risk of hemorrhage<a class="elsevierStyleCrossRef" href="#tblfn0030">a</a>: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypertensive patients with high cardiovascular risk, defined by: LVH, microalbuminuria/proteinuria, renal failure, increased pulse wave velocity, increased IMT, presence of vascular atheroma plaque, pathological ABI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diabetic and hypertensive patients with microalbuminuria/proteinuria regardless of the presence of the remaining subclinical disease markers. It might also be considered in the absence of hypertension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365563.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0030" "etiqueta" => "a" "nota" => "Some members of the panel of experts stated that the dosages and indications of the Polypill ingredients separately should be taken into consideration." ] ] ] "descripcion" => array:1 [ "en" => "Profile of high or very high risk patients with subclinical cardiovascular disease." ] ] 8 => array:8 [ "identificador" => "tbl0045" "etiqueta" => "Table 9" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at9" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "A: Agreement % y (n); ARB: angiotensin II receptor blocker; DR: degree of recommendation; ACEI: Angiotensin-converting-enzyme inhibitor; LE: level of evidence." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on ARB replacement by the ACEI of Polypill \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A (No.) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE/DR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">27. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ARBs can be replaced by an ACEI, except in cases in which the patient previously presented any side effect with an ACE-inhibitor, such as cough or angioneurotic edema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1++/A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib1040">84–86,105,106</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365564.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the administration of Polypill in patients taking statins other than atorvastatin \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A (No.) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE/DR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">28. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In patients taking statins other than atorvastatin,<a class="elsevierStyleCrossRef" href="#tblfn0035">a</a> they might be replaced by Polypill, as long as the LDL-C lowering power is maintained in comparable terms (moderate hypocholesterolemic intensity) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4/D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRef" href="#bib1170">110</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">29. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In patients requiring higher therapeutic intensity than with atorvastatin 20mg<a class="elsevierStyleCrossRef" href="#tblfn0035">a</a> the replacement in statins can not be recommended because the loss of hypocholesterolemic effect can be accompanied by an increased risk and lower benefit of the hypocholesterolemic treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2+/D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRef" href="#bib1175">111</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">30. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">It is necessary to consider an individualized therapeutic approach before a therapeutic replacement, taking into account the objectives of LDL-C in terms of individual risk, as advocated by the European guidelines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4/D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib1020">80,110</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365570.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0035" "etiqueta" => "a" "nota" => "Equivalent doses of different statins for reducing LDL-c by 41% as is the case of atorvastatin 20mg,<a class="elsevierStyleCrossRef" href="#bib1160">108</a> lovastatin: 80mg pitavastatin: 4mg, pravastatin 80mg, rosuvastatin: 5mg and simvastatin 40mg." ] ] ] "descripcion" => array:1 [ "en" => "Recommendations on replacing drugs by the Polypill ingredients." ] ] 9 => array:8 [ "identificador" => "tbl0050" "etiqueta" => "Table 10" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at10" "detalle" => "Table 1" "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "A: agreement% y (n); ASA: acetylsalicylic acid; DR: degree of recommendation; LE: level of evidence." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the administration of Polypill \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A (No.) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE/DR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">31. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">It is recommended that Polypill be taken as a single daily capsule, preferably after a meal to decrease the potential gastrointestinal side effects of ASA<a class="elsevierStyleCrossRef" href="#tblfn0040">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">87% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1+/A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRefs" href="#bib0940">64,114,120–124</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">32. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polypill should be swallowed with some beverage. Do not chew or crush before swallowing. Do not open the capsule since the closure system guarantees the pharmacological properties of the active ingredients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1+/A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon,<a class="elsevierStyleCrossRefs" href="#bib0940">64,114</a>Available at:http://www.aemps.gob.es/cima/pdfs/es/ft/72375/FT_72375.pdf<a class="elsevierStyleCrossRefs" href="#bib1220">120–124</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">33. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">If you forget to take a dose, take your usual dose when the next \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">34. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Taking into account the characteristics of its 3 ingredients, it is not expected that the effect of Polypill significantly decreases when forgetting one intake \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">√ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based on the opinion of the expert panel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365571.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0040" "etiqueta" => "a" "nota" => "A member of the panel of experts emphasized that drug intake should be individualized in each patient depending on their characteristics and personal circumstances." ] ] ] "descripcion" => array:1 [ "en" => "Recommendations on the administration of Polypill." ] ] 10 => array:8 [ "identificador" => "tbl0055" "etiqueta" => "Table 11" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at11" "detalle" => "Table 1" "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "A: agreement% y (n); DR: degree of recommendation; LE: level of evidence." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on lifestyle habits and behaviors in patients treated with the Polypill \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A (No.) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE/DR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">35. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Heart-healthy lifestyle habits is, together with pharmacological treatment, the basis of the prevention and treatment of coronary disease. The cornerstones of heart-healthy lifestyle are: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2++/B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Not using toxic substances \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Heart-healthy diet \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Regular physical exercise \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Prevent from obesity especially central obesity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Control of associated standard cardiovascular risk factors (diabetes, hypertension, dyslipidemia) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRef" href="#bib1195">115</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">36. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In addition, educational and cardiac rehabilitation programs are necessary to promote a healthy lifestyle \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4/D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ref. source \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Based upon<a class="elsevierStyleCrossRef" href="#bib1195">115</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1365559.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Recommendations on lifestyle habits and behaviors in patients treated with the Polypill." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:124 [ 0 => array:3 [ "identificador" => "bib0625" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "937.e1–937.e66" "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Guía europea sobre prevención de la enfermedad cardiovascular en la práctica clínica (versión 2012)" ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Rev Esp Cardiol" "fecha" => "2012" "volumen" => "65" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0630" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "European Cardiovascular Disease Statistics 2012" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:2 [ "fecha" => "2012" "editorial" => "European Heart Network, Brussels, European Society of Cardiology, Sophia Antipolis European Heart" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0635" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nota de prensa: Defunciones según la causa de muerte año 2012" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2014" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0640" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coste económico de las enfermedades cardiovasculares desde 2014–2020 en 6 países europeos" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2014" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0645" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Joint WHO/FAO expert consultation on diet, nutrition and the prevention of chronic diseases" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2002" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0650" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adherence to long-term therapies: evidence for action" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2003" "editorial" => "World Health Organization" "editorialLocalizacion" => "Geneva" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0655" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An alarming threat to secondary prevention: low compliance (lifestyle) and poor adherence (drugs)" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Esp Cardiol (Engl Ed)" "fecha" => "2012" "volumen" => "65" "numero" => "Suppl. 2" "paginaInicial" => "10" "paginaFinal" => "16" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0660" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variations in patients’ adherence to medical recommendations: a quantitative review of 50 years of research" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Med Care" "fecha" => "2004" "volumen" => "42" "paginaInicial" => "200" "paginaFinal" => "209" "link" => array:1 [ …1] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0665" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of placebo adherence on reducing cardiovascular mortality: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00392-013-0642-6" "Revista" => array:6 [ "tituloSerie" => "Clin Res Cardiol" "fecha" => "2014" "volumen" => "103" "paginaInicial" => "229" "paginaFinal" => "235" "link" => array:1 [ …1] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0670" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adherence to statin or aspirin or both in patients with established cardiovascular disease: exploring healthy behaviour vs. drug effects and 10-year follow-up of outcome" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2125.2008.03212.x" "Revista" => array:6 [ "tituloSerie" => "Br J Clin Pharmacol" "fecha" => "2008" "volumen" => "66" "paginaInicial" => "110" "paginaFinal" => "116" "link" => array:1 [ …1] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0675" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictors of long-term adherence to evidence-based cardiovascular disease medications in outpatients with stable atherothrombotic disease: findings from the REACH Registry" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/clc.22217" "Revista" => array:6 [ "tituloSerie" => "Clin Cardiol" "fecha" => "2013" "volumen" => "36" "paginaInicial" => "721" "paginaFinal" => "727" …1 ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0680" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-compliance with digoxin in patients with heart failure and/or atrial fibrillation: a systematic review and meta-analysis of observational studies" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.acvd.2012.06.004" "Revista" => array:6 [ …6] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0685" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aiming at strategies for a complex problem of medical nonadherence" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.gheart.2013.06.001" "Revista" => array:6 [ …6] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0690" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A polypill strategy to improve global secondary cardiovascular prevention: from concept to reality" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2014.06.009" "Revista" => array:6 [ …6] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0695" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A polypill strategy to improve adherence: results from the FOCUS project" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2014.08.021" "Revista" => array:6 [ …6] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0700" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Medication nonfulfillment rates and reasons: narrative systematic review" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1185/03007990903550586" "Revista" => array:6 [ …6] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0705" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Medication nonadherence: a diagnosable and treatable medical condition" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2013.4638" "Revista" => array:6 [ …6] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0710" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adherence to medication" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMra050100" "Revista" => array:6 [ …6] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0715" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A meta-analysis of the association between adherence to drug therapy and mortality" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmj.38875.675486.55" "Revista" => array:5 [ …5] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0720" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Self-reported medication adherence and cardiovascular events in patients with stable coronary heart disease: the heart and soul study" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archinte.167.16.1798" "Revista" => array:6 [ …6] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0725" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(11)61215-4" "Revista" => array:6 [ …6] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0730" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "357 e357–357 e327" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The impact of medication adherence on coronary artery disease costs and outcomes: a systematic review" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ …3] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0735" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fixed-dose combinations improve medication compliance: a meta-analysis" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.amjmed.2006.08.033" "Revista" => array:6 [ …6] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0740" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ficha técnica de Trinomia 100mg/20mg/10mg cápsulas duras" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ …1] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0745" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Métodos de consenso. Uso adecuado de la evidencia en la toma de decisiones. Método RAND/UCLA" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ …5] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0750" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Available in: http://www.sign.ac.uk/guidelines/fulltext/50/index.html [accessed 03.05.13]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "SIGN 50: a guideline developers’ handbook" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ …3] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0755" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Available in: http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ [accessed 09.10.14]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Levels of evidence" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ …1] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0760" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "AGREE II: advancing guideline development, reporting and evaluation in health care" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ …5] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0765" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Untangling the relationship between medication adherence and post-myocardial infarction outcomes: medication adherence and clinical outcomes" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ahj.2013.09.014" "Revista" => array:6 [ …6] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0770" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Statin treatment non-adherence and discontinuation: clinical implications and potential solutions" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0775" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The economic consequences of noncompliance in cardiovascular disease and related conditions: a literature review" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1742-1241.2007.01683.x" "Revista" => array:6 [ …6] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0780" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Full coverage for preventive medications after myocardial infarction" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMsa1107913" "Revista" => array:6 [ …6] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0785" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of medication adherence on hospitalization risk and healthcare cost" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0790" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The incidence and determinants of primary nonadherence with prescribed medication in primary care: a cohort study" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/M13-1705" "Revista" => array:6 [ …6] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0795" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Level of unawareness and management of diabetes, hypertension, and dyslipidemia among adults in Luxembourg: findings from ORISCAV-LUX study" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0057920" "Revista" => array:5 [ …5] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0800" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Patient and physician related factors of adherence to evidence based guidelines in diabetes mellitus type 2, cardiovascular disease and prevention: a cross sectional study" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2296-14-47" "Revista" => array:5 [ …5] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0805" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Patients’ adherence to secondary prevention pharmacotherapy after acute coronary syndromes" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11096-012-9735-y" "Revista" => array:6 [ …6] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0810" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined secondary prevention after hospitalization for myocardial infarction in France: analysis from a large administrative database" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.acvd.2009.02.005" "Revista" => array:6 [ …6] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0815" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guideline-recommended secondary prevention drug therapy after acute myocardial infarction: predictors and outcomes of nonadherence" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/HJR.0b013e328338e5da" "Revista" => array:6 [ …6] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0820" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Concerns about medications mediate the association of posttraumatic stress disorder with adherence to medication in stroke survivors" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjhp.12022" "Revista" => array:6 [ …6] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0825" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interventions for enhancing medication adherence" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ …3] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0830" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Can simple clinical measurements detect patient noncompliance?" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0835" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adherencia al tratamiento en el paciente anciano" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ …5] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0840" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Medicines adherence: involving patients in decisions about prescribed medicines and supporting adherence. NICE clinical guideline 76" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ …1] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0845" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Misperceptions of patients vs providers regarding medication-related communication issues" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0850" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Physician assessments of patient compliance with medical treatment" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0855" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metodología de estudios del incumplimiento terapéutico" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:4 [ …4] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0860" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Validity of four indirect methods to measure adherence in primary care hypertensives" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.jhh.1002196" "Revista" => array:6 [ …6] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0865" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "96–97" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How to detect and manage low patient compliance in chronic illness" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0870" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Concurrent and predictive validity of a self-reported measure of medication adherence" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0875" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Stages of change in the modification of problem behaviors" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0880" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "El incumplimiento terapéutico como problema relacionado con medicamentos diferenciado" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ …5] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0885" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cumplimiento de la prescripción farmacológica en pacientes hipertensos" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ …5] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0890" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Review of the test used for measuring therapeutic compliance in clinical practice" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0895" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev-pharmtox-011711-113247" "Revista" => array:6 [ …6] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0900" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How often is medication taken as prescribed? A novel assessment technique" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0905" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacist intervention to improve medication adherence in heart failure: a randomized trial" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0910" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interventions promoting adherence to cardiovascular medicines" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11096-012-9607-5" "Revista" => array:6 [ …6] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0915" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of a pharmacist-led intervention on diuretic compliance in heart failure patients: a randomized controlled study" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0920" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of intervention through a pharmaceutical care program on patient adherence with prescribed once-daily atorvastatin" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/pds.1198" "Revista" => array:6 [ …6] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0925" "etiqueta" => "61" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Strategies to improve drug adherence" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehq297" "Revista" => array:6 [ …6] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0930" "etiqueta" => "62" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of medication dosing frequency on adherence in chronic diseases" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 62 => array:3 [ "identificador" => "bib0935" "etiqueta" => "63" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Could the polypill improve adherence? The patient perspective" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 63 => array:3 [ "identificador" => "bib0940" "etiqueta" => "64" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Trinomia. The polypill for secondary prevention of cardiovascular events" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ …1] ] ] ] ] ] 64 => array:3 [ "identificador" => "bib0945" "etiqueta" => "65" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dosing frequency and medication adherence in chronic disease" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.18553/jmcp.2012.18.7.527" "Revista" => array:6 [ …6] ] ] ] ] ] 65 => array:3 [ "identificador" => "bib0950" "etiqueta" => "66" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of dosing frequency on chronic cardiovascular disease medication adherence" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1185/03007995.2012.677419" "Revista" => array:6 [ …6] ] ] ] ] ] 66 => array:3 [ "identificador" => "bib0955" "etiqueta" => "67" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/2047487315569401" "Revista" => array:6 [ …6] ] ] ] ] ] 67 => array:3 [ "identificador" => "bib0960" "etiqueta" => "68" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fixed-dose compounds and the secondary prevention of ischemic heart disease" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.recesp.2011.02.027" "Revista" => array:7 [ …7] ] ] ] ] ] 68 => array:3 [ "identificador" => "bib0965" "etiqueta" => "69" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fixed-dose combination therapy for the prevention of cardiovascular disease" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ …4] ] ] ] ] ] 69 => array:3 [ "identificador" => "bib0970" "etiqueta" => "70" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The combined use of aspirin, a statin, and blood pressure-lowering agents (polypill components) and the risk of vascular morbidity and mortality in patients with coronary artery disease" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ahj.2013.04.011" "Revista" => array:6 [ …6] ] ] ] ] ] 70 => array:3 [ "identificador" => "bib0975" "etiqueta" => "71" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase ii, double-blind, randomised trial" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(09)60611-5" "Revista" => array:6 [ …6] ] ] ] ] ] 71 => array:3 [ "identificador" => "bib0980" "etiqueta" => "72" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of a secondary prevention combination therapy with an aspirin, an ACE inhibitor and a statin on 1-year mortality of patients with acute myocardial infarction treated with a beta-blocker. Support for a polypill approach" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1185/03007995.2011.590969" "Revista" => array:6 [ …6] ] ] ] ] ] 72 => array:3 [ "identificador" => "bib0985" "etiqueta" => "73" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2013.277064" "Revista" => array:6 [ …6] ] ] ] ] ] 73 => array:3 [ "identificador" => "bib0990" "etiqueta" => "74" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Projected impact of polypill use among US adults: medication use, cardiovascular risk reduction, and side effects" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ahj.2010.12.019" "Revista" => array:6 [ …6] ] ] ] ] ] 74 => array:3 [ "identificador" => "bib0995" "etiqueta" => "75" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Available in http://www.revespcardiol.org/es/utilidad-un-policomprimido-cardiovascular-eneltratamiento/avance-resumen/S0300-8932(16)30217-2/" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Utilidad de un policomprimido cardiovascular en el tratamiento de pacientes en prevención secundaria en España: un estudio de coste-efectividad" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ …2] ] ] ] ] ] 75 => array:3 [ "identificador" => "bib1000" "etiqueta" => "76" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR)" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/2047487316653709" "Revista" => array:6 [ …6] ] ] ] ] ] 76 => array:3 [ "identificador" => "bib1005" "etiqueta" => "77" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/eht296" "Revista" => array:6 [ …6] ] ] ] ] ] 77 => array:3 [ "identificador" => "bib1010" "etiqueta" => "78" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/eht151" "Revista" => array:6 [ …6] ] ] ] ] ] 78 => array:3 [ "identificador" => "bib1015" "etiqueta" => "79" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts)" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehs092" "Revista" => array:6 [ …6] ] ] ] ] ] 79 => array:3 [ "identificador" => "bib1020" "etiqueta" => "80" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ESC/EAS guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS)" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehr158" "Revista" => array:6 [ …6] ] ] ] ] ] 80 => array:3 [ "identificador" => "bib1025" "etiqueta" => "81" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevention: Polypills for cardiovascular prevention: a step forward?" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrcardio.2013.157" "Revista" => array:6 [ …6] ] ] ] ] ] 81 => array:3 [ "identificador" => "bib1030" "etiqueta" => "82" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Polypill and global cardiovascular health strategies" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.semtcvs.2011.05.005" "Revista" => array:6 [ …6] ] ] ] ] ] 82 => array:3 [ "identificador" => "bib1035" "etiqueta" => "83" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Should all patients at high cardiovascular risk receive renin–angiotensin system blockers?" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/qjmed/hcr190" "Revista" => array:6 [ …6] ] ] ] ] ] 83 => array:3 [ "identificador" => "bib1040" "etiqueta" => "84" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/HJH.0b013e3281fc975a" "Revista" => array:6 [ …6] ] ] ] ] ] 84 => array:3 [ "identificador" => "bib1045" "etiqueta" => "85" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reappraisal of European guidelines on hypertension management: A European Society of Hypertension Task Force document" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/HJH.0b013e328333146d" "Revista" => array:6 [ …6] ] ] ] ] ] 85 => array:3 [ "identificador" => "bib1050" "etiqueta" => "86" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/01.HYP.0000107251.49515.c2" "Revista" => array:6 [ …6] ] ] ] ] ] 86 => array:3 [ "identificador" => "bib1055" "etiqueta" => "87" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(04)16895-5" "Revista" => array:6 [ …6] ] ] ] ] ] 87 => array:3 [ "identificador" => "bib1060" "etiqueta" => "88" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(12)60367-5" "Revista" => array:6 [ …6] ] ] ] ] ] 88 => array:3 [ "identificador" => "bib1065" "etiqueta" => "89" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(02)09327-3" "Revista" => array:6 [ …6] ] ] ] ] ] 89 => array:3 [ "identificador" => "bib1070" "etiqueta" => "90" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(08)60104-X" "Revista" => array:6 [ …6] ] ] ] ] ] 90 => array:3 [ "identificador" => "bib1075" "etiqueta" => "91" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characteristics and lipid distribution of a large, high-risk, hypertensive population: the lipid-lowering component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ …5] ] ] ] ] ] 91 => array:3 [ "identificador" => "bib1080" "etiqueta" => "92" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(03)12948-0" "Revista" => array:6 [ …6] ] ] ] ] ] 92 => array:3 [ "identificador" => "bib1085" "etiqueta" => "93" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Statins for the primary prevention of cardiovascular disease" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ …4] ] ] ] ] ] 93 => array:3 [ "identificador" => "bib1090" "etiqueta" => "94" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(09)60503-1" "Revista" => array:6 [ …6] ] ] ] ] ] 94 => array:3 [ "identificador" => "bib1095" "etiqueta" => "95" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Collaborative overview of randomised trials of antiplatelet therapy – I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration" ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 95 => array:3 [ "identificador" => "bib1100" "etiqueta" => "96" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 96 => array:3 [ "identificador" => "bib1105" "etiqueta" => "97" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Additive benefits of pravastatin and aspirin to decrease risks of cardiovascular disease: randomized and observational comparisons of secondary prevention trials and their meta-analyses" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archinte.164.1.40" "Revista" => array:6 [ …6] ] ] ] ] ] 97 => array:3 [ "identificador" => "bib1110" "etiqueta" => "98" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term statin safety and efficacy in secondary prevention: can combination therapy improve outcomes?" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 98 => array:3 [ "identificador" => "bib1115" "etiqueta" => "99" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ …3] ] ] ] ] ] 99 => array:3 [ "identificador" => "bib1120" "etiqueta" => "100" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Available in: http://www.nice.org.uk/guidance/PH25" "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Prevention of cardiovascular disease at population level" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ …1] ] ] ] ] ] 100 => array:3 [ "identificador" => "bib1125" "etiqueta" => "101" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(09)60503-1" "Revista" => array:6 [ …6] ] ] ] ] ] 101 => array:3 [ "identificador" => "bib1130" "etiqueta" => "102" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomized Polypill crossover trial in people aged 50 and over" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0041297" "Revista" => array:5 [ …5] ] ] ] ] ] 102 => array:3 [ "identificador" => "bib1135" "etiqueta" => "103" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy (‘polypill’) on cardiovascular risk factors" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1742-1241.2010.02412.x" "Revista" => array:6 [ …6] ] ] ] ] ] 103 => array:3 [ "identificador" => "bib1140" "etiqueta" => "104" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combination pharmacotherapy to prevent cardiovascular disease: present status and challenges" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/eht407" "Revista" => array:6 [ …6] ] ] ] ] ] 104 => array:3 [ "identificador" => "bib1145" "etiqueta" => "105" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Angiotensin II receptor blockers and myocardial infarction: an updated analysis of randomized clinical trials" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/HJH.0b013e32832961ed" "Revista" => array:6 [ …6] ] ] ] ] ] 105 => array:3 [ "identificador" => "bib1150" "etiqueta" => "106" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Telmisartan, ramipril, or both in patients at high risk for vascular events" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0801317" "Revista" => array:6 [ …6] ] ] ] ] ] 106 => array:3 [ "identificador" => "bib1155" "etiqueta" => "107" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmj.326.7404.1423" "Revista" => array:5 [ …5] ] ] ] ] ] 107 => array:3 [ "identificador" => "bib1160" "etiqueta" => "108" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dyslipidemia and its therapeutic challenges in renal transplantation" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1600-6143.2012.04084.x" "Revista" => array:6 [ …6] ] ] ] ] ] 108 => array:3 [ "identificador" => "bib1165" "etiqueta" => "109" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.jhh.1001748" "Revista" => array:6 [ …6] ] ] ] ] ] 109 => array:3 [ "identificador" => "bib1170" "etiqueta" => "110" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/01.cir.0000437738.63853.7a" "Revista" => array:7 [ …7] ] ] ] ] ] 110 => array:3 [ "identificador" => "bib1175" "etiqueta" => "111" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical implications of switching from intensive to moderate statin therapy after acute coronary syndromes" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijcard.2010.07.006" "Revista" => array:6 [ …6] ] ] ] ] ] 111 => array:3 [ "identificador" => "bib1180" "etiqueta" => "112" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New AHA and ACC guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00508-014-0513-9" "Revista" => array:6 [ …6] ] ] ] ] ] 112 => array:3 [ "identificador" => "bib1185" "etiqueta" => "113" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment compliance in chronic illness: current situation and future perspectives" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.rce.2014.03.008" "Revista" => array:6 [ …6] ] ] ] ] ] 113 => array:3 [ "identificador" => "bib1190" "etiqueta" => "114" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Ficha técnica Trinomia [cited March 2015]." ] ] ] 114 => array:3 [ "identificador" => "bib1195" "etiqueta" => "115" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => 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Consensus statement

Consensus document for the use of the Polypill in the secondary prevention of cardiovascular disease

Documento de consenso del uso clínico de la Polypill en la prevención secundaria del riesgo cardiovascular

José Ramón González-Juanateya,

Corresponding author

Jose.Ramon.Gonzalez.Juanatey@sergas.es

Corresponding author.

, José María Mostazab, José María Lobosc, Benjamín Abarcad, José Luis Llisterrie, Gonzalo Baron-Esquiviasa, Enrique Galvea, Rosa María Lidóna, Francisco Xavier Garcia-Molla, Pedro Luis Sáncheza, Carmen Suárezb, Jesús Millánb, Vicente Pallarese, José Juan Alemánc, Isabel Egocheagad

a Sociedad Española de Cardiología, Madrid, Spain

b Sociedad Española de Medicina Interna, Madrid, Spain

c Sociedad Española de Medicina de Familia y Comunitaria, Barcelona, Spain

d Sociedad Española de Médicos Generales y de Familia, Madrid, Spain

e Sociedad Española de Médicos de Atención Primaria, Madrid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Cardiovascular disease</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cardiovascular disease &#40;CVD&#41; includes ischemic diseases of heart&#44; brain and peripheral vascular system&#46; Its main substrate is atheromatosis&#44; a chronic disorder that develops insidiously throughout life and is usually advanced when the first symptoms appear&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">1</span></a> CVD often begins with an acute episode due to an atherothrombotic complication in the form of acute coronary syndromes &#40;including sudden death in 15&#8211;20&#37; cases&#41; and stroke&#44; as major manifestations&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">2</span></a> The fact that the first &#40;or successive&#41; clinical manifestations may be lethal or highly disabling emphasizes the need for primary and secondary prevention&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Although cardiovascular &#40;CV&#41; mortality has dropped considerably in recent decades in many European countries&#44; CVD causes 4 million deaths in Europe every year and over 1&#46;9 million deaths in the European Union&#46; Therefore&#44; it is the major cause of premature death&#46; 40&#37; of all deaths in the European Union are due to CVD&#44;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">2</span></a> while in Spain they account for 30&#46;3&#37; of all deaths&#44; being the leading cause of death&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">CVD causes a high number of disability cases and will continue to be the major cause of loss in productivity&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">1</span></a> In Spain it is estimated that health care costs of CVD will increase from 5&#46;9 million euros in 2014 to 8&#46;8 million euros in 2020&#44; with hospitalization being responsible for approximately 50&#37; of health care costs&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">CVD is strongly related to lifestyle&#44; especially with smoking&#44; unhealthy eating habits&#44; physical inactivity and psychosocial stress&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">5</span></a> The chronicity of these patients is a determinant in the decision making regarding their follow-up and treatment&#46; The high rates of rehospitalization and morbidity and mortality in the short term after hospital discharge in patients treated on CV events show the need to stress on the help and follow-up required by these patients after discharge&#46; CVD prevention is key to stop the occurrence of CVD&#44; and is defined as a series of coordinated actions&#44; both in population and individuals&#44; aimed at eradicating&#44; eliminating or minimizing the impact of CVD and their associated disability&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">1</span></a> Prevention is typically defined as primary prevention and secondary prevention&#46; However&#44; in CVD distinction between these two categories is arbitrary because of the underlying and progressive nature of the atherosclerotic process&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">For understanding the dynamics of the CV epidemic it is important to differentiate between the effect of a decrease in mortality and changes related to the prevention of clinical episodes&#46; It has been shown that prevention of CVD through various lifestyle and pharmacological preventive strategies works&#46; Specifically&#44; over 50&#37; of the reduction in CV mortality is related to the modification of risk factors and 40&#37; to the improvement of treatments&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">1</span></a> In spite of this&#44; in the developed countries the application of these preventive measures is much lower than expected&#46; One of the aspects to improve is the lack of therapeutic compliance of patients&#44; which limits the potential benefit that might be obtained through prevention&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Concept of adherence to therapy</span><p id="par0030" class="elsevierStylePara elsevierViewall">The World Health Organization defines the adherence to a long-term therapy as the degree of adherence to the pharmacological treatment&#44; the follow-up of a diet and&#47;or changes in lifestyle to comply with the recommendations agreed upon with the doctor or other health professionals&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">6</span></a> Thus&#44; adherence involves both taking the medication properly &#40;in accordance with the prescribed dosage and schedule&#41; and lifestyle modifications over time&#46; And&#44; unlike compliance&#44; implies the patient&#39;s active participation&#46;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">6&#8211;8</span></a> Adherence to therapy is a complex behavior process that has been defined as&#58; &#8220;An active&#44; voluntary and collaborative involvement of the patient in a course on behavior to produce a therapeutic result&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">It is estimated that the number of patients with good adherence in secondary prevention of CVD is generally low and that it decreases progressively over time&#46;<a class="elsevierStyleCrossRefs" href="#bib0670"><span class="elsevierStyleSup">10&#8211;12</span></a> On average&#44; after 6 months of effective treatment&#44; over 50&#37; patients decide to suspend their treatment and lifestyle modifications&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">13</span></a> The lack of adherence to therapy&#44; and therefore&#44; not complying with the therapeutic goals&#44; has a high impact on the health of the patient and entails a high economic cost due to the increase of hospitalization and death rates&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">14</span></a> There are many reasons leading to the lack of adherence to pharmacological treatment<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">13&#44;15&#8211;18</span></a> such as those related to the patient&#39;s own personal situation&#44; chronicity and the asymptomatic character of the disease itself&#44; the lack of doctor&#8211;patient communication&#44; or lack of accessibility to medical services&#44; etc&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The direct association between adherence to the prescribed pharmacological treatment and the degree of control of chronic diseases and the incidence of CV episodes&#44; leading to higher or lower morbidity and mortality&#44; is currently known&#46;<a class="elsevierStyleCrossRefs" href="#bib0715"><span class="elsevierStyleSup">19&#44;20</span></a> Lack of adherence to therapy is a major global problem in both developed and developing countries<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">21</span></a> and is one of the obstacles to improving patients&#8217; health and quality of life and reducing costs of Health and Social care&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">22</span></a> Support instead of blaming the patient&#44; simplifying treatment&#44; better doctor&#8211;patient communication and a multidisciplinary approach taking into account the preferences of the patient&#44; might provide solutions tailored to each individual case&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Polypill</span><p id="par0045" class="elsevierStylePara elsevierViewall">Preventing CVD by using <span class="elsevierStyleItalic">fixed-dose combination therapies</span> has gained increasing momentum as a strategy to stop the progression of the disease&#46; Including key medications necessary to reduce cardiovascular risk &#40;CVR&#41; in a single capsule or tablet&#44; once-daily&#44; can improve adherence to therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">23</span></a> The results of clinical trials have supported the viability of these therapies in the prevention and management of CVD although with some warnings&#44; essentially related to the lack of evidence on the effect of these therapies to effectively reduce CV events&#46; There are currently several ongoing clinical trials that will provide definitive evidence on the effectiveness of these combinations&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">14</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The Polypill for secondary prevention of CVD is the first fixed-dose combination therapy approved in Europe indicated for the secondary prevention of CV events as a replacement treatment in adult patients adequately controlled with the monoingredients administered concomitantly in equivalent therapeutic doses&#46; The capsule includes 3 active ingredients&#58; acetylsalicylic acid &#40;ASA&#41; 100<span class="elsevierStyleHsp" style=""></span>mg&#44; atorvastatin 20<span class="elsevierStyleHsp" style=""></span>mg and ramipril 2&#46;5&#44; 5 or 10<span class="elsevierStyleHsp" style=""></span>mg&#46; In Spain&#44; its price includes the price of its 3 ingredients&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">24</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Purpose of the consensus document and field of application</span><p id="par0055" class="elsevierStylePara elsevierViewall">The purpose of this consensus document is to define and recommend&#44; through evidence available in the literature and the opinion of health professionals&#44; <span class="elsevierStyleItalic">the impact of non-adherence to therapy for secondary prevention of CVD and the potential use of a Polypill in the daily clinical practice of these patients</span>&#59; Without forgetting that the use of a fixed-dose combination therapy should not make ignore the need to maintain an adequate lifestyle&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The recommendations in this document are aimed at all those specialists&#44; cardiologists&#44; internists and primary care practitioners authorized to prescribe and monitor patients with high and very high CVR and requiring secondary prevention of CVD&#44; or high-risk patients&#44; or very high CVR requiring treatment with antiplatelet&#44; hypolipidemic and antihypertensive drugs&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Methodology used in the document</span><p id="par0065" class="elsevierStylePara elsevierViewall">The consensus was performed using RAND&#47;UCLA methodology&#46;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">25</span></a> This consensus method is based on the scientific evidence and the collective judgment and clinical experience of a panel of experts&#46; The purpose of this method is to promote the critical discussion of experts&#44; through the individual reflection of a questionnaire and a new group discussion on the consensuses and disagreements reached in the individual reflection&#44; through a face-to-face&#44; structured and participatory session&#46; In order to define the degree of acceptance of the recommendations&#44; a percentage agreement was established&#46; The recommendations were classified as &#8220;unanimously accepted&#8221; if the entire panel of experts agreed&#44; &#8220;accepted by consensus&#8221; if over 80&#37; agreed &#8220;in discrepancy&#8221;&#44; accepted by 66&#8211;79&#37; and &#8220;rejected&#8221; when it was approved by less than 66&#37;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Finally&#44; a final recommendation report was drafted&#46; This document included both the agreements and disagreements after the consensus phase&#46; The recommendations were accompanied by the final percentage agreement obtained in the last vote&#46; The final report was validated and approved by the participants&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In order to evaluate the levels of scientific evidence and degrees of recommendation&#44; the modified SIGN method<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">26</span></a> was used&#44; using the Oxford Centre for Evidence-Based Medicine system<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">27</span></a> for diagnostic questions and the SIGN system for the remaining questions &#40;treatment&#44; prognosis&#44; etc&#46;&#41; &#40;<a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#41;&#46; <span class="elsevierStyleItalic">In addition&#44; whenever possible&#44; AGREE</span><a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">28</span></a><span class="elsevierStyleItalic">was used when drafting the document&#46;</span></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Recommendations</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Impact of lack of adherence on cardiovascular health</span><p id="par0080" class="elsevierStylePara elsevierViewall">The non-symptomatic and chronic nature of CVD&#44; drug co-payment&#44; complex therapeutic schedules or not in accordance with current clinical practice guidelines and the lack of educational programs for professionals and patients<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">7</span></a> would explain&#44; among other causes&#44; the lack of adherence to therapy and perpetuity of CVD as the main cause of global morbidity and mortality in a setting with high economic cost&#46; <span class="elsevierStyleItalic">The increase in the rate of major CV events</span>&#44;<a class="elsevierStyleCrossRefs" href="#bib0765"><span class="elsevierStyleSup">29&#8211;31</span></a><span class="elsevierStyleItalic">the increase in healthcare burden and in health costs</span><a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">32</span></a><span class="elsevierStyleItalic">are the consequences of this lack of adherence to therapy</span> &#40;LE&#58; 2&#43;&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The lack of adherence to therapy results in a higher CV morbidity and mortality&#44; both in primary and secondary prevention of CVD&#44;<a class="elsevierStyleCrossRefs" href="#bib0765"><span class="elsevierStyleSup">29&#8211;31</span></a> as well as a higher rate of hospital admissions and readmissions&#46;<a class="elsevierStyleCrossRefs" href="#bib0775"><span class="elsevierStyleSup">31&#44;33</span></a><span class="elsevierStyleItalic">Therefore&#44; lack of adherence to therapy has been shown to increase the rate of major CV events&#44; both in primary &#40;LE&#58; 2&#43;&#41; and secondary prevention of CVD &#40;LE&#58; 1</span>&#8722;<span class="elsevierStyleItalic">&#41;&#44; which implies poorer quality of life for patients&#46;</span><a class="elsevierStyleCrossRefs" href="#bib0765"><span class="elsevierStyleSup">29&#8211;31&#44;33</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">On the other hand&#44; within the CVR&#44; CVD implies risk factors&#44; related clinical conditions&#44; or comorbidities&#44;<a class="elsevierStyleCrossRefs" href="#bib0785"><span class="elsevierStyleSup">33&#44;34</span></a> such as hypertension &#40;HT&#41;&#44; dyslipidemia or diabetes mellitus&#46; Thus&#44; non-adherence to therapy for one of these conditions may lead to non-adherence to other therapies&#46; There is also evidence that non-adherent patients are less likely to attend medical visits&#44;<a class="elsevierStyleCrossRefs" href="#bib0790"><span class="elsevierStyleSup">34&#44;35</span></a> which would imply the loss of possibilities for an early &#40;and opportunistic&#41; diagnosis of other CVR-related or non-CVR-related diseases&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The frequency of medical visits is directly related to adherence to therapy&#44; which is greater in patients with a higher number of medical visits with a prescription&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">34</span></a> The patient&#39;s lack of confidence in initiating a new therapy may lead to a lower number of visits to the physician&#46;<a class="elsevierStyleCrossRefs" href="#bib0655"><span class="elsevierStyleSup">7&#44;36</span></a> In addition&#44; patients non-adherent to their treatment&#44; due to lack of trust&#47;communication with their doctor&#44; usually do not attend or attend fewer visits compared to adherent patients&#46;<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">35</span></a><span class="elsevierStyleItalic">Despite this&#44; the lack of adherence to therapy increases the burden of care due to the greater complexity of complications and hospital admissions</span><a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">14</span></a> &#40;LE&#58; 1&#43;&#43;&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Likewise&#44; non-adherence to pharmacological therapy entails a high cost of healthcare arising mainly from hospitalization &#40;which accounts for approximately 50&#37; of the cost&#41; and&#44; secondly&#44; pharmaceutical costs&#46;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">4&#44;7&#44;33</span></a> Furthermore&#44; it is a major cause of the inefficient healthcare system<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">4&#44;7</span></a> because of the increase in direct costs as a result of CVD &#40;costs of admission&#44; emergency visits&#44; outpatient hospital care&#44; etc&#46;&#41; and the increase in indirect costs &#40;early mortality and morbidity&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">It is important to emphasize the need for studies that evaluate the cost-effectiveness not only of treatment&#44; but also of pharmacological interventions&#44; which has been termed as the &#8220;size of treatment effects&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">31</span></a> The available studies do not really reflect the magnitude of the problem because they evaluate the cost-effectiveness of a particular treatment&#44; regardless of compliance&#44; or because they fail to investigate the effect size&#44; particularly because compliance and effectiveness of treatment are unknown&#46; <span class="elsevierStyleItalic">Thus&#44; adherence is a key factor in ensuring the sustainability of the healthcare system&#44; since non-adherence is linked to poorer health outcomes and higher costs for the system</span><a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">4&#44;7&#44;33</span></a><span class="elsevierStyleItalic">&#40;LE&#58;</span> 2&#43;&#43;&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Adherence to therapy in secondary prevention and in patients of high&#44; or very high risk with subclinical cardiovascular disease</span><p id="par0110" class="elsevierStylePara elsevierViewall">Despite all improvements in both the therapeutic and the CVD outcomes&#44; the lack of adherence to medication indicated in chronic diseases continues to be an important barrier in the secondary prevention of CVD&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleItalic">The lack of time and resources devoted to the patient&#39;s health education&#44; the difficulty of access to cardiac rehabilitation programs&#44; the awareness of the physician and the patient self-awareness of the disease and care</span> are factors that determine the lack of adherence in secondary prevention and in high or very high risk patients with subclinical CVD&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Adherence to therapy is more closely correlated with the type of disease or therapeutic schedule than with the patient&#39;s demographic characteristics &#40;age&#44; sex&#44; education&#44; and income level&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">18</span></a> Several studies have shown low adherence in different patient profiles&#46; Thus the FOCUS study<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">15</span></a> concludes that the low adherence to a complex pharmacological treatment of patients who have suffered an acute myocardial infarction is associated with a young age and depression&#46; &#40;LE&#58; 1&#43;&#43;&#41;&#46; In terms of secondary prevention&#44; poor adherence has been reported in&#58; elderly&#44; unemployed patients&#44; with higher comorbidity&#44; polypharmacy&#44; multivascular disease&#44; non-interventional treatment&#44; etc&#46;<a class="elsevierStyleCrossRefs" href="#bib0675"><span class="elsevierStyleSup">11&#44;37&#8211;39</span></a> &#40;LE&#58; 2&#8722;&#41;&#46; Patients who have suffered an acute coronary syndrome or an intervention are more adherent than those who have suffered a stroke&#44; probably due to the cognitive&#47;physical worsening associated with the latter&#46; In addition&#44; some authors show that non-adherence to medication in patients with post-traumatic stress arising from stroke may be due to concern or fear of drugs<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">40</span></a> &#40;LE&#58; 2&#8722;&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> lists the recommendations on these determinants&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Actions to measure adherence to therapy</span><p id="par0120" class="elsevierStylePara elsevierViewall">It is crucial to be provided with reliable methods for measuring and evaluating adherence to therapy efficiently&#44; so that the necessary preventive and&#47;or corrective actions can be taken&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">A great variety of strategies have been described to assess the therapeutic adherence of patients with chronic diseases&#44; although their specific measurement shows many difficulties&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">18</span></a> Most studies conducted to evaluate strategies aimed at improving adherence measures overestimate the degree of adherence&#46;<a class="elsevierStyleCrossRefs" href="#bib0825"><span class="elsevierStyleSup">41&#44;42</span></a> Direct and indirect methods have been described and applied&#46; The former are poorly applicable to standard clinical practice and the latter are simpler and more applicable&#44; but limited because of their low sensitivity and moderate specificity&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Direct methods for assessing pharmacological adherence &#40;such as blood or urine drug levels&#44; direct observation of intake&#44; etc&#46;&#41; are expensive&#44; complex and poorly applicable to routine clinical practice&#46; Therefore&#44; their use is practically relegated to the field of research&#46;<a class="elsevierStyleCrossRefs" href="#bib0835"><span class="elsevierStyleSup">43&#44;44</span></a> &#40;LE&#58; 4&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The most simple indirect method is the method based on the <span class="elsevierStyleItalic">opinion of the professional</span>&#46; However it has been proven not sufficiently valid as the only tool to assess adherence&#44; not only because of the subjectivity that it entails&#44; but mainly because of the deficiencies in doctor&#8211;patient communication&#46; 74&#37; physicians believe their patients are taking the prescribed medication and 83&#37; patients do not inform their practitioner about their adherence to therapy&#46; Therefore&#44; there is little agreement between doctors&#8217; perception on the quality of their communication with their patients and the actual information that the patients report to their doctor&#46;<a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">45&#44;46</span></a> &#40;LE&#58; 2&#43;&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The indirect method based on the <span class="elsevierStyleItalic">counting of tablets</span> compares the number of tablets remaining in the package in a scheduled appointment&#44; taking into account the prescribed tablets and the time elapsing between the prescription and the counting&#44; and thus obtain the compliance rate considering 80&#8211;110&#37; as good adherence&#46;<a class="elsevierStyleCrossRefs" href="#bib0835"><span class="elsevierStyleSup">43&#44;47</span></a> For some authors it is considered as a reference method&#46;<a class="elsevierStyleCrossRef" href="#bib0860"><span class="elsevierStyleSup">48</span></a> It can be used to confirm suspected noncompliance&#44; but it has the limitation that when the patients are feeling observed&#44; they improve their adherence&#46; Specific devices for the counting of tablets are currently available &#40;Monitors Events Medication Systems&#41; which are containers recording every opening and are subsequently analyzed by computer &#40;LE&#58; 2&#43;&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Another indirect method widely recommended is the <span class="elsevierStyleItalic">personalized clinical interview</span>&#46; The technique usually used is self-test questionnaire&#46; The most used tests are the Haynes and Sackett test&#44;<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">49</span></a> the Moriski&#8211;Green&#8211;Levine test<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">50</span></a> and the Prochasca&#8211;Diclemente test&#46;<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">51</span></a> Although other national tests &#40;such as Herrera Carranza<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">52</span></a> and Batalla<a class="elsevierStyleCrossRef" href="#bib0885"><span class="elsevierStyleSup">53</span></a> tests&#41; have been developed&#44; different method validation studies performed in our country for the assessment of adherence through a clinical interview conclude that these methods are not very useful&#44; showing little consistency with the method of counting tablets&#46; They are a very reliable method if the patient declares himself to be non-compliant&#44; and is therefore very useful to inquire about the reasons for non-adherence&#46;<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">54</span></a> These results are consistent with other international studies<a class="elsevierStyleCrossRefs" href="#bib0825"><span class="elsevierStyleSup">41&#44;42</span></a> &#40;LE&#58; 2&#43;&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In recent years the <span class="elsevierStyleItalic">electronic medical record</span> has been implemented in practically all of our country&#44; and afterwards the <span class="elsevierStyleItalic">electronic prescription</span>&#44; which allows access to the containers that patients withdraw from the pharmacy offices&#44; resulting in a method of easy applicability in clinical practice&#46; It is currently considered as a valid method for the quantification of adherence and allows to explore the dosage from the beginning of the prescription and confirm the persistence in adherence over time&#46; Poor adherence may be detected as a result of intermittent drop-outs in dosing and usually underestimated by other methods&#46; However&#44; these non-compliances can be clinically acknowledged in the event of intermittent failures in treatment efficacy<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">55</span></a> &#40;LE&#58; 4&#41;&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Another indirect method to assess adherence&#44; frequently used in clinical practice but with fewer comparative studies&#44; is assessing the therapeutic effect of the prescribed drugs &#40;and also its known and expected side effects&#41;&#44; such as modifications in heart rate&#44; blood pressure &#40;BP&#41;&#44; blood glucose&#44; body weight&#44; etc&#46;&#44; as well as attendance at scheduled control visits &#40;LE&#58; 4&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">To date&#44; the methods described are the most commonly used in clinical practice for the assessment of therapeutic adherence&#46; None of them are considered ideal since all have advantages and disadvantages&#46; Combining various methods can significantly increase the validity of the results<a class="elsevierStyleCrossRefs" href="#bib0895"><span class="elsevierStyleSup">55&#44;56</span></a> &#40;LE&#58; 4&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows recommendations on the existing actions to measure therapeutic adherence&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Actions to optimize adherence to therapy</span><p id="par0165" class="elsevierStylePara elsevierViewall">Bearing in mind the positive effect of adherence to placebo&#44; proven even in clinical variables&#44;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">9</span></a> patient adherence is more than just a single drug intake&#46; Therefore&#44; intervention strategies aimed at improving adherence should include aspects other than the drugs involved&#46; The improvement and persistence of adherence to CV drugs is a dynamic process influenced by many factors&#46; One of them is that multiple interventions of reinforcement are required systematically over time&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">55</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The strategies evaluated to improve adherence mainly include behavioral interventions&#44; information to patients&#44; use of fixed-dose combination therapies to reduce the number of daily tablets required and combined strategies&#46; Some of these intervention strategies have been proven effective in improving adherence and&#47;or persistence in the CVD field&#46; Since there is evidence that pharmacological adherence decreases significantly during the first 6 months after prescription&#44;<a class="elsevierStyleCrossRefs" href="#bib0655"><span class="elsevierStyleSup">7&#44;13</span></a> these months are a critical and decisive time to act on this problem&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Other strategies are aimed at achieving persistence in adherence to therapy&#46; These strategies include mailing video programs or newsletters providing information&#44; multimedia educational programs&#44; review of medications with the patient&#44; follow-up with phone contacts or videophone&#44; &#8220;pillbox with Alarm&#8221; warning of the time to take medication&#44; etc&#46; In general&#44; complex interventions have provided moderate improvements and simple interventions have shown little or no effect&#46; And all of them have shown a pattern of <span class="elsevierStyleItalic">loss of efficacy through time</span>&#44; requiring reinforcement strategies&#46;<a class="elsevierStyleCrossRefs" href="#bib0895"><span class="elsevierStyleSup">55&#44;57</span></a> Numerous interventions to improve adherence in chronic CV disease have been shown to be effective&#44; such as <span class="elsevierStyleItalic">reducing copayment&#44; automated reminders&#44; mail-orders to pharmacies&#44; health care counseling&#44; and fixed-dose combination therapy</span><a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">30</span></a> &#40;LE&#58; 1&#43;&#41;&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">A review of the literature identified numerous intervention studies to improve adherence to CV drugs in patients with hypertension&#44; dyslipidemia&#44; congestive heart failure or coronary disease in the community setting&#46; These studies were based on providing information-education&#44; in behavioral programs&#44; social intervention and combined interventions&#46; <span class="elsevierStyleItalic">Behavioral interventions</span> have been shown to be most effective &#40;compared to other types of interventions&#41;&#44; whereas adding information strategies has not led to further improvements in adherence<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">58</span></a> &#40;LE&#58; 1&#43;&#41;&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">A new strategy to improve drug adherence and health outcomes is the use of <span class="elsevierStyleItalic">management services</span> &#40;electronic or otherwise&#41; of therapeutic drug plans by pharmacists or other health care providers&#46; Several studies have shown significant improvements in adherence to CV drugs&#46; However&#44; interventions in treatment management require a complex approach involving a patient-focused approach&#44; reinforcement interventions and multidisciplinary participation<a class="elsevierStyleCrossRefs" href="#bib0905"><span class="elsevierStyleSup">57&#44;59&#44;60</span></a> &#40;LE&#58; 1&#43;&#41;&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The most current and most frequently used interventions in routine clinical practice to improve patient adherence are focused primarily on correcting the amount of daily tablets&#46;<a class="elsevierStyleCrossRefs" href="#bib0665"><span class="elsevierStyleSup">9&#44;61</span></a> Simplifying the dosing schedule is perhaps the intervention with greater effectiveness evidence&#46; There are many evidences showing a direct association between the complexity of the prescribed treatment &#40;in terms of dosage&#44; route of administration&#44; number of drugs&#44; etc&#46;&#41; and adherence&#46; A systematic review of 20 randomized clinical trials concludes that reducing the dosing frequency in patients with chronic diseases improves therapeutic adherence<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">62</span></a> &#40;LE&#58; 1&#43;&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">In this context of simplifying therapeutic regimens&#44; <span class="elsevierStyleItalic">fixed-dose combination therapies</span> are a complementary strategy to improve adherence in many types of diseases&#46; In addition&#44; it reduces production and distribution costs and improves the affordability of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">7</span></a> In addition&#44; patients included in studies involving a fixed-dose combination therapy show a favorable perception toward said therapy<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">63</span></a> &#40;LE&#58; 2&#43;&#41;&#46; Therefore&#44; it can be stated that simplifying treatment is an effective strategy&#44; since most studies have found significant improvements in the adherence rate and in the process control in the group of patients where the therapeutic schedule for CV prevention was simplified&#47;facilitated<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">64</span></a> &#40;NS&#58; 1&#43;&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the recommendations regarding actions to be taken to optimize therapeutic adherence&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Fixed-dose combination therapies improve therapeutic adherence</span><p id="par0200" class="elsevierStylePara elsevierViewall">Several studies have shown that not all patients receive the appropriate drugs for secondary prevention of CVD&#46; In addition&#44; as mentioned above&#44; a higher number of daily doses and tablets is associated with lower compliance&#46; The effect of fixed-dose combinations on a single tablet on the improvement in therapeutic adherence has been studied in different contexts and <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> summarizes the main studies&#58;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0205" class="elsevierStylePara elsevierViewall">As reported in the results of several studies shown in the table above&#44; it has been proven that fixed-dose combination therapies improve therapeutic adherence with respect to free treatments&#46; Simplifying administration and reducing the number of drugs contribute to therapeutic adherence&#46;<a class="elsevierStyleCrossRefs" href="#bib0945"><span class="elsevierStyleSup">65&#8211;67</span></a> In addition&#44; the potential value of applying the concept of fixed-dose combination therapy for secondary prevention of CVD has been acknowledged by different panels of experts &#40;World Health Organization and Combination Pharmacotherapy and Public Health Research Working Group&#41;&#46; In summary&#44; the use of fixed-dose combination therapy simplifies the onset and maintenance of treatment in patients in secondary prevention and in high CVR&#46; In addition&#44; replacing the drugs indicated for secondary or primary prevention of CVD in patients with high CVR by a single daily dose combination improves the therapeutic adherence&#44; the availability and the efficiency of the preventive treatment&#46; <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a> lists the recommendations on these determinants&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Expected benefits in <span class="elsevierStyleItalic">Polypill</span> patients</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">In patients with no or little adherence to therapy&#44; in secondary cardiovascular prevention</span><p id="par0210" class="elsevierStylePara elsevierViewall">The reduction of CV episodes with ASA&#44; ramipril and statins has been proven in the medical literature and&#44; in addition&#44; it is known that the prognostic relevance of the 3 drugs together is higher than that of each drug separately&#46;<a class="elsevierStyleCrossRef" href="#bib0960"><span class="elsevierStyleSup">68</span></a> As we have seen previously&#44; reducing the number of drugs might help increase compliance&#44; which would lead to improved prognosis for patients with poor compliance&#46; There have been some studies on primary and secondary prevention of CVD in terms of the usefulness of fixed-dose combination therapies&#44; although none of them have been carried out with the 3 ingredients of the Polypill&#46; Some of these studies are limited in the sample studied and others are still in the data collection and follow-up phase&#46; Therefore&#44; the results are also limited&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">14</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Some investigations with fixed-dose combination therapies have shown improvements in systolic BP&#44; number of vascular episodes and total mortality in individuals taking these treatments<a class="elsevierStyleCrossRefs" href="#bib0965"><span class="elsevierStyleSup">69&#8211;72</span></a> &#40;LE&#58; 1&#43;&#43;&#41;&#46; In the UMPIRE study&#44; <span class="elsevierStyleItalic">mild but statistically significant improvements occurred in systolic BP and LDL-C</span> in patients with fixed-dose combination therapies compared to routine treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0985"><span class="elsevierStyleSup">73</span></a> It is estimated that&#44; in the United States alone&#44; the use of a fixed-dose combination therapy with the active ingredients commonly used and with proven effectiveness in individual formulations can prevent 3&#46;2 million CV episodes and 1&#46;7 million strokes&#46;<a class="elsevierStyleCrossRef" href="#bib0990"><span class="elsevierStyleSup">74</span></a> However&#44; these effects on reducing CV episodes have recently been questioned in a systematic Cochrane review that grouped studies on primary and secondary prevention of CVD&#46; In this review no benefit was shown for fixed-dose combination therapies for the prevention of CV events&#46; However&#44; a great heterogeneity was observed in the results&#44; not explained by the fact of mixing studies on primary and secondary prevention of CVD&#46; In the same study&#44; <span class="elsevierStyleItalic">BP and lipid parameters dropped more</span> in the group of fixed-dose combination therapies&#44; although the results were also very heterogeneous<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">69</span></a> &#40;LE&#58; 1&#43;&#43;&#41;&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">A cost-effectiveness study has recently been published with Spanish data comparing the use of the CV Polypill versus its ingredients separately&#46; The results&#44; based on an increased therapeutic adherence and&#44; therefore&#44; higher effectiveness in the real world&#44; show that the treatment with CV Polypill would additionally prevent from 46 non-lethal CV episodes &#40;including 17&#46;48 acute coronary syndromes&#44; 19&#46;62 revascularizations&#44; 6&#46;99 strokes&#41; and 11 lethal cases per 1000 treated patients&#46; In addition&#44; a strategy that includes Polypill is a dominant strategy &#40;higher effectiveness and lower cost than the use of the ingredients separately&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0995"><span class="elsevierStyleSup">75</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Polypill&#44; which contains drugs of proven prognostic efficacy&#44; can improve adherence&#44; becoming an interesting CV prevention strategy&#46; In addition&#44; it has been developed in a very specific conceptual framework to improve adherence&#44; accessibility&#44; effectiveness&#44; and therefore cost-effectiveness&#44; and has been tested in clinical studies&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">15</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In summary&#44; <span class="elsevierStyleItalic">simplifying the therapeutic regimen is accompanied by best results in terms of therapeutic adherence and best control of CVR factors&#44; both in primary and secondary prevention</span><a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">14</span></a> &#40;LE&#58; 1&#43;&#41;&#46; <span class="elsevierStyleItalic">However&#44; no differences were found in clinical episodes&#44; probably because it was not the purpose of the studies&#44; because of the limited sample size of the studies and the low number of episodes</span><a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleItalic">&#40;LE&#58; 1&#43;&#43;&#41;&#46;</span></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">In adherent patients on secondary prevention of cardiovascular disease</span><p id="par0235" class="elsevierStylePara elsevierViewall">Recently the European guidelines for the prevention of CVD in clinical practice has been published<a class="elsevierStyleCrossRef" href="#bib1000"><span class="elsevierStyleSup">76</span></a> which includes the recommendation of using Polypill to improve adherence&#46; Additionally&#44; this guidelines also makes hygiene and dietary recommendations and usually includes a section where it is recommended that the patient know and understand their treatment&#46; As in the case of non-adherent or poorly adherent patients&#44; &#8220;<span class="elsevierStyleItalic">the advantage that can be expected from a fixed-dose combination therapy is the simplification of the therapeutic regimen&#44; particularly in polypharmacy patients and with comprehension difficulties</span>&#8221;&#46; <span class="elsevierStyleItalic">Specifically&#44; in the group of patients with good therapeutic adherence&#44; fixed-dose combination therapy simplifies treatment and may encourage long-term adherence&#46;</span></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Identifying clinical situations in cardiovascular secondary prevention tributary of the administration of Polypill</span><p id="par0240" class="elsevierStylePara elsevierViewall">For all of the above mentioned&#44; Polypill can be very useful in certain contexts to promote therapeutic adherence&#46; Clinical situations in CV secondary prevention have been reported where administration of Polypill would bring benefits and include patients with coronary events &#40;acute&#44; chronic&#44; and revascularized or not&#41;&#44; patients with ischemic stroke&#44; and patients with symptomatic peripheral artery disease&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">The clinical criteria that might determine the indication of Polypill in secondary prevention of CVD&#44; would be patients with a history of non-adherence or with some of the predictors of pharmacological non-adherence&#59; Patients controlled with the individual drugs&#59; Patients with poor control with equipotent doses and with adherence problems and&#44; finally&#44; patients with multiple diseases and polypharmacy patients&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Timing for prescribing Polypill</span><p id="par0250" class="elsevierStylePara elsevierViewall">Although there are no studies that have addressed the optimal time to start treatment with Polypill&#44; experts agree that the following should be evaluated&#58; combination therapy at the acute stage of the ischemic event&#59; if difficulties are predicted on patient adherence&#44; on accessibility to treatment or on follow-up&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">The therapeutic purposes for secondary prevention of CVD in patients with confirmed coronary disease are well described in the clinical practice guidelines of all scientific societies&#46; These therapeutic purposes include healthy lifestyle habits in both physical exercise and eating habits&#44; as well as the control of CVR factors with BP levels &#60;140&#47;90<span class="elsevierStyleHsp" style=""></span>mmHg&#44; and LDL-c &#60;70<span class="elsevierStyleHsp" style=""></span>mg&#47;DL &#40;1&#46;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41; or a &#8805;50&#37; reduction in baseline LDL-c levels&#46; It is important to emphasize that these therapeutic purposes must be maintained throughout the patient&#39;s life&#46;<a class="elsevierStyleCrossRefs" href="#bib1005"><span class="elsevierStyleSup">77&#8211;80</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">In patients who are already being treated with the different drugs separately&#44; <span class="elsevierStyleItalic">replacing triple therapy by Polypill</span> would improve patient adherence and might be used as a strategy to improve control of CVR factors and therefore decrease vascular episodes&#46;<a class="elsevierStyleCrossRefs" href="#bib1025"><span class="elsevierStyleSup">81&#44;82</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">Because of these circumstances&#44; and in the specific case of Polypill&#44; the main determinants to replace an individualized therapy by Polypill are mainly the non-compliance of the subject&#44; the difficulty of access to treatments&#44; polypharmacy or the economic advantages that this might imply&#46; In all cases&#44; it should be guaranteed &#40;as far as possible&#41; that the therapeutic response for proper levels of LDL-c and BP be obtained with Polypill&#46; Otherwise&#44; we should evaluate the possibility of separately adding the necessary extra dose of complementary medication or return to the individualized treatment&#46; But&#44; previously it should be verified that not complying with the purposes is not due to non-compliance with the treatment with Polypill&#44; since it might worsen as the number of drugs increases&#46; <a class="elsevierStyleCrossRef" href="#tbl0035">Table 7</a> lists the recommendations on the timing to prescribe Polypill and replacement to Polypill and vice versa&#46;</p><elsevierMultimedia ident="tbl0035"></elsevierMultimedia></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Clinical situations where Polypill would not be indicated</span><p id="par0270" class="elsevierStylePara elsevierViewall">Of the 3 ingredients used in Polypill&#44; atorvastatin is offered in a single 20<span class="elsevierStyleHsp" style=""></span>mg dose&#46; Such a dose might be adequate but&#44; in a number of patients&#44; it may not have the therapeutic potency to obtain the therapeutic goals indicated in the clinical practice guidelines&#46; Ramipril is the only Polypill ingredient that allows a titration according to the patient&#39;s requirements as it is offered in 3 different doses &#40;2&#46;5&#44; 5 and 10<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46; But&#44; like atorvastatin it may not have the power necessary to comply with the therapeutic purposes in patients with difficult HT control&#46; On the other hand&#44; each ingredient of Polypill &#40;ASA 100<span class="elsevierStyleHsp" style=""></span>mg&#44; atorvastatin 20<span class="elsevierStyleHsp" style=""></span>mg and ramipril at 3 different doses&#41; might cause side effects and specific contraindications&#44; although the adverse effects of each ingredient manifest clinically differently and might be identified relatively easily&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Although we can state that Polypill offers proven effectiveness and greater adherence to therapy there are 2 scenarios in which its administration would not be indicated&#46; These situations are defined in patients where treatment with Polypill does not obtain the therapeutic purposes indicated by the guidelines of clinical practice or at least an acceptable approach to those objectives and in those patients with adverse effects to one of the 3 ingredient of Polypill &#40;LE&#58; &#8730;&#44; based on expert opinion with 83&#37; agreement&#41;&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Specific clinical situations that may benefit from Polypill</span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Profile of high or very high risk patients with subclinical cardiovascular disease</span><p id="par0280" class="elsevierStylePara elsevierViewall">CVD is a continuum ranging from the presence of risk factors in isolation to disease clinically reported &#40;including the acute episode&#41;&#44; from subclinical disease or asymptomatic lesion of the target organs&#46; The presence of <span class="elsevierStyleItalic">subclinical CVD</span>&#44; defined as the presence of organ damage&#44; left ventricular hypertrophy&#44; kidney failure&#44; microalbuminuria&#47;proteinuria&#44; increased media intima thickness&#44; atherosclerotic plaque&#44; lower ankle-brachial index&#44; etc&#46; places patients at a high or very high CVR level&#46; This makes them&#44; in most cases&#44; candidates for a pharmacological intervention&#44; not only for the control of their risk factors but also for organ protection&#44; not being enough the treatment aimed at modifying the lifestyle&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">Blockade of the renin&#8211;angiotensin&#8211;aldosterone system is one of the interventions that have been proven beneficial in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib1035"><span class="elsevierStyleSup">83</span></a> Both ACEI and ARBs have demonstrated&#44; in addition to lowering BP&#44; the ability to provide organic protection at vascular&#44; cardiac and kidney levels&#46;<a class="elsevierStyleCrossRefs" href="#bib1040"><span class="elsevierStyleSup">84&#8211;86</span></a> Several ACE inhibitors &#40;enalapril&#44; lisinopril&#44; quinapril&#44; ramipril and trandolapril&#41; and ARBs &#40;candesartan&#44; valsartan and losartan&#41; are indicated in patients with left ventricular dysfunction or clinical heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib1035"><span class="elsevierStyleSup">83</span></a> However&#44; only telmisartan and ramipril are indicated to reduce CVR based on clinical trials&#46;<a class="elsevierStyleCrossRef" href="#bib1035"><span class="elsevierStyleSup">83</span></a> Ramipril is indicated in CV prevention to reduce CV morbidity and mortality in patients with proven atherothrombotic disease or diabetes with at least one RCV factor<a class="elsevierStyleCrossRef" href="#bib1035"><span class="elsevierStyleSup">83</span></a> &#40;LE&#58; 4&#41;&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">Statins are also drugs that have been shown to provide organic protection in patients with high CVR in primary prevention of CVD&#46;<a class="elsevierStyleCrossRefs" href="#bib1055"><span class="elsevierStyleSup">87&#8211;93</span></a> &#40;LE&#58; 1&#43;&#43;&#41;&#46; The benefit of antiaggregation&#44; however&#44; is controversial in primary prevention&#46; Therefore&#44; it should be individualized in every case&#44; depending on the expected risk&#47;benefit&#46; While in secondary prevention their benefit is proven&#44; in primary prevention they may only be recommended in patients with high CVR and low risk of hemorrhage&#46;<a class="elsevierStyleCrossRefs" href="#bib1090"><span class="elsevierStyleSup">94&#8211;96</span></a> &#40;LE&#58; 1&#43;&#43;&#41;&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Despite the CVR of patients with subclinical CVD&#44; the asymptomatic nature of their disease and the lack of a previous CV episode have an influence on the poor compliance and lack of adherence to the prescribed treatment&#46; Therefore&#44; many of these patients may benefit from a therapeutic strategy that facilitates compliance such as fixed-dose combination therapy&#44; consisting of those pharmacological ingredients that have been proven beneficial in the presence of subclinical CV disease&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">As previously discussed&#44; the use of a fixed-dose combination therapy may reduce CV morbidity and mortality<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">69</span></a> &#40;LE&#58; 1&#43;&#43;&#41; and although there is no definitive evidence of the ingredients that should be part of these treatments&#44; there is consensus that they should include a renin&#8211;angiotensin&#8211;aldosterone system blocker and a statin<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">69</span></a> &#40;LE&#58; 1&#43;&#43;&#41;&#46; In addition&#44; 2 systematic reviews&#47;meta-analyzes have been proven to have an effect on CV protection&#44; combining ASA with statins&#46;<a class="elsevierStyleCrossRefs" href="#bib1105"><span class="elsevierStyleSup">97&#44;98</span></a> &#40;LE&#58; 1&#43;&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0040">Table 8</a> lists the recommendations in this subtype of patients&#46;</p><elsevierMultimedia ident="tbl0040"></elsevierMultimedia></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Profile of high or very high risk patients without established or subclinical cardiovascular disease</span><p id="par0305" class="elsevierStylePara elsevierViewall">Primary prevention of CVD is aimed at preventing from CV episodes in patients without CVD symptomatology&#46; In patients with a high CVR&#44; clinical practice guidelines recommend the use of statins and antihypertensive drugs to reduce this CVR and vascular accidents&#46;<a class="elsevierStyleCrossRefs" href="#bib1015"><span class="elsevierStyleSup">79&#44;99&#44;100</span></a> In the case of ASA&#44; the third ingredient of the Polypill&#44; the controversy over its benefit in primary prevention of CVD is more significant due to the lack of clear evidence of a favorable benefit&#47;risk ratio in these patients&#46; Nevertheless&#44; some publications mention that in patients with high CVR&#44; the clinical benefit might be obtained when the absolute risk is reduced above the risk of hemorrhage&#46;<a class="elsevierStyleCrossRef" href="#bib1125"><span class="elsevierStyleSup">101</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">There is some evidence on the effectiveness and safety of the use of fixed-dose combination therapies in patients with primary prevention of CVD&#46;<a class="elsevierStyleCrossRefs" href="#bib0975"><span class="elsevierStyleSup">71&#44;102&#8211;104</span></a> However&#44; the lack of specific evidence in the case of Polypill caused a debate among the group of experts due to the controversial use of ASA in these patients&#46; This is why the panel of experts did not reach consensus on the possibility of recommending Polypill in all patients on primary prevention of CVD&#44; being exclusively recommended in certain patients with very high RCV &#40;see previous section&#41;&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Replacement of an angiotensin II receptor blocker by the Polypill angiotensin converting enzyme inhibitor</span><p id="par0315" class="elsevierStylePara elsevierViewall">There are different pharmacological groups capable of blocking the renin&#8211;angiotensin&#8211;aldosterone system&#44; with ACEIs and ARBs being the main ones&#46; As previously mentioned&#44; both ACEIs and ARBs have been proven capable of providing organic protection at vascular&#44; cardiac and kidney levels&#44; in addition to lowering BP<a class="elsevierStyleCrossRefs" href="#bib1040"><span class="elsevierStyleSup">84&#8211;86</span></a> &#40;LE&#58; 4&#41;&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">Although its mechanism of action is different&#44; its effectiveness and safety are similar from a CV point of view&#46; These two pharmacological groups are mainly different because of the best tolerability of ARBs&#44; mainly due to the lower incidence of cough&#44; a side effect that occurs in less than 10&#37; of those treated with ACE inhibitors and which is related to its effect on bradykinins&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">The effect of ARBs on the risk of myocardial infarction has been analyzed in a meta-analysis of 20 clinical trials involving a total 109&#44;000 patients&#44; been proved to have the same capacity as ACE inhibitors to reduce the risk of Myocardial infarction &#40;OR&#58; 1&#46;008&#44; CI 95&#37;&#58; 0&#46;926&#8211;1&#46;099&#41;<a class="elsevierStyleCrossRef" href="#bib1145"><span class="elsevierStyleSup">105</span></a> &#40;LE&#58; 1&#43;&#43;&#41;&#46; Direct comparisons&#44; such as in the ONTARGET<a class="elsevierStyleCrossRef" href="#bib1150"><span class="elsevierStyleSup">106</span></a> trial&#44; in patients with high CVR do not find differences between ACE inhibitors and ARBs in their protective effect on CV morbidity and mortality&#46; In this study&#44; telmisartan and ramipril were equivalent in their protective effect on CV episodes &#40;LE&#58; 1&#43;&#41;&#46; Based on this&#44; the European Hypertension Guidelines concluded in 2007 that both pharmacological groups were interchangeable from a point of view of CV protection<a class="elsevierStyleCrossRefs" href="#bib1010"><span class="elsevierStyleSup">78&#44;85</span></a> &#40;LE&#58; 4&#41;&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">In summary&#44; there is sufficient evidence based on clinical trials showing that there are no differences in the organic protection provided by ACE inhibitors and ARBs&#46; The main difference is in the higher incidence of cough with ACE inhibitors &#40;see recommendations in <a class="elsevierStyleCrossRef" href="#tbl0045">Table 9</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0045"></elsevierMultimedia></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Replacement between statins</span><p id="par0335" class="elsevierStylePara elsevierViewall">Statins are useful in secondary prevention of CVD and in the control of LDL-C levels and are recommended by clinical practice guidelines<a class="elsevierStyleCrossRefs" href="#bib1015"><span class="elsevierStyleSup">79&#44;80</span></a> &#40;LE&#58; 1&#43;&#43;&#41;&#46; Specifically&#44; atorvastatin 20<span class="elsevierStyleHsp" style=""></span>mg&#44; with a hypocholesterolemic potency reducing LDL-C by 41&#8211;43&#37;<a class="elsevierStyleCrossRefs" href="#bib1155"><span class="elsevierStyleSup">107&#44;108</span></a> is the most used statin&#44; with a proper balance between efficacy and adverse effects<a class="elsevierStyleCrossRef" href="#bib1165"><span class="elsevierStyleSup">109</span></a> &#40;LE&#58; 1&#43;&#43;&#41;&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">In high CVR situations &#40;secondary prevention of CVD&#44; diabetes mellitus with other risk factors or target organ damage&#44; high risk primary prevention of CVD&#41;&#44; statin therapies always require potent high dose statins to try to achieve C-LDL reduction purposes<a class="elsevierStyleCrossRefs" href="#bib1015"><span class="elsevierStyleSup">79&#44;110</span></a> &#40;LE&#58; 4&#41;&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">In patients in secondary prevention of CVD&#44; statin doses may be reduced in up to 42&#37; patients due to adverse effects or safety reasons&#46; These decreases in the dose of statins cause a reduction of the hypocholesterolemic effect&#44; and may be accompanied by increased CVR<a class="elsevierStyleCrossRefs" href="#bib1175"><span class="elsevierStyleSup">111&#44;112</span></a> &#40;LE&#58; 2&#43;&#41; &#40;see recommendations in <a class="elsevierStyleCrossRef" href="#tbl0045">Table 9</a>&#41;&#46;</p></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Polypill limitations&#44; precautions and contraindications</span><p id="par0350" class="elsevierStylePara elsevierViewall">In the context of any chronic pharmacological treatment it is important to consider the disadvantages and risks of administering fixed-dose drugs by means of Polypill&#46; What happens if we do not comply with the therapeutic purposes indicated in the clinical guidelines&#44; both in very high-risk patients and patients after an ischemic episode&#63; What should we do if the patient begins to have side effects to any ingredient of the Polypill &#40;e&#46;g&#46; gastrointestinal side effects caused by ASA&#44; cough caused by ACEI&#44; and myopathies or enzyme elevation for statins&#44; etc&#46;&#41;&#63; Can the occurrence of side effects make the patient stop taking the medication and lose the hypothetical benefit of all the pharmacological ingredients of Polypill&#63; Can the combination of several drugs and their excipients cause adverse effects other than each drug individually&#63;</p><p id="par0355" class="elsevierStylePara elsevierViewall">Although there are currently no publications on the adverse effects of Polypill&#44; the Cochrane systematic review conducted to evaluate other fixed-dose combination therapies for CV prevention<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">69</span></a> showed that &#40;LE&#58; 1&#43;&#43;&#41;&#44; the reduction in BP and lipid parameters is higher than expected&#46; In addition&#44; the use of fixed-dose combination therapies is associated with mild increases in the frequency of side effects &#40;30&#37;&#41;&#44; compared to placebo or with the use of drugs administered individually&#44; which are mostly not serious&#44; mainly because there are more patients taking the medication&#46; Approximately half of the patients with side effects treated with fixed-dose combination therapies discontinue their use&#46; Treatment discontinuation in fixed-dose combination therapies is 14 vs 11&#37; in individuals treated with placebo &#40;RR&#58; 1&#46;26&#44; CI 95&#37;&#58; 1&#46;02&#8211;1&#46;55&#41;&#46; Finally&#44; the increase in the therapeutic adherence to fixed-dose combination therapy is associated to the benefit in complying with the therapeutic purposes&#44; and explains the increased incidence of side effects&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">Therefore&#44; the panel of experts concludes that&#58; <span class="elsevierStyleItalic">The disadvantages and risks of administering fixed doses by means of Polypill are to not comply with the required or optimal control purposes&#46; However&#44; the use of fixed-dose combination therapies is associated with a higher reduction in BP and lipid values than expected&#44; due to the increased therapeutic adherence&#46; In addition&#44; there is insufficient data to determine the frequency of adverse effects for Polypill&#44; as compared to the 3 drugs separately&#46; However&#44; in other studies&#44; the use of other fixed-dose combination therapies has been associated with mild increase in the frequency of non-serious side effects compared to use of the drugs separately&#44; and this can be attributed to the improved adherence</span><a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">69</span></a> &#40;LE&#58; 1&#43;&#43;&#41;&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">Regarding the precautions for treatment with Polypill &#40;ASA&#44; ramipril and atorvastatin&#41;&#44; the Polypill datasheet&#44; currently available under the name Trinomia<span class="elsevierStyleSup">&#174;</span>&#44; details the warnings for special populations&#44; the need for monitoring during treatment and warnings about specific adverse reactions&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">24</span></a></p><p id="par0370" class="elsevierStylePara elsevierViewall">Therefore&#44; <span class="elsevierStyleItalic">precautions in the use of the Polypill in CV prevention are specified in its datasheet and arise from the precautions in the use of ASA&#44; ramipril and atorvastatin&#46;</span></p><p id="par0375" class="elsevierStylePara elsevierViewall">In addition&#44; some experts consider it appropriate to emphasize that an <span class="elsevierStyleItalic">increased risk of adverse effects should not be expected as a result of interactions between them and that the patient should understand that simplifying treatment is not synonymous with detracting from it&#46;</span></p><p id="par0380" class="elsevierStylePara elsevierViewall">Skipping one dose is the most frequent cause of unintended therapeutic non-compliance&#46;<a class="elsevierStyleCrossRef" href="#bib1185"><span class="elsevierStyleSup">113</span></a> Since the approved dosing regimen for Polypill is the same as that of its 3 ingredients separately&#44;<a class="elsevierStyleCrossRef" href="#bib1190"><span class="elsevierStyleSup">114</span></a> the recommendations to be followed are specified in the data sheet since no short-term consequences are anticipated given the half-life of each of them &#40;LE&#58; 1&#43;&#41; &#40;see recommendations in <a class="elsevierStyleCrossRef" href="#tbl0050">Table 10</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0050"></elsevierMultimedia></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Habits and behaviors of the patient under treatment with Polypill</span><p id="par0385" class="elsevierStylePara elsevierViewall">Even though the patient follows an adequate therapeutic regimen&#44; there remains a residual risk of a similar magnitude&#44; or higher&#44; compared to the risk that has been eliminated&#44; due in part to the genetic load and unsuitable lifestyles&#46; Therefore drugs&#44; in our case Polypill&#44; should be associated with lifestyle habits and behaviors that contribute to reduce residual risk and limit the gene expression leading to the progression of the disease and&#47;or to developing new acute processes&#46; Therefore&#44; patients treated pharmacologically in both primary and secondary prevention of CVD require lifestyle heart-healthy habits&#44; including<a class="elsevierStyleCrossRef" href="#bib1195"><span class="elsevierStyleSup">115</span></a> quitting smoking and other toxic substances such as cocaine&#44; in addition to inadequate alcohol consumption &#40;LE&#58; 1&#43;&#44; B&#41;&#44; following a heaart-healthy diet &#40;LE&#58; 1&#43;&#43;&#44; DR&#58; A&#41;&#44; practice regular moderate physical exercise&#44; 2<span class="elsevierStyleHsp" style=""></span>h 30<span class="elsevierStyleHsp" style=""></span>min a week or 75<span class="elsevierStyleHsp" style=""></span>min of intense aerobic exercise &#40;LE&#58; 1&#43;&#44; DR&#58; B&#41;&#44; normal body weight with a BMI ranging from 18 to 25<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> &#40;LE&#58; 1&#43;&#44; DR&#58; B&#41;&#46; Finally&#44; following cardiac training and rehabilitation programs that favor physical activity and heart-healthy lifestyle habits are extremely useful tools that have also been shown to be effective in adherence to pharmacological treatment &#40;LE&#58; 2&#43;&#43;&#44; DR&#58; B&#41; &#40;see recommendations in <a class="elsevierStyleCrossRef" href="#tbl0055">Table 11</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0055"></elsevierMultimedia><p id="par0390" class="elsevierStylePara elsevierViewall">The use of drugs proven efficient in secondary prevention of CVD has been increased&#46; However&#44; poor adherence to healthy lifestyles&#44; and the fact that it does not improve through the years&#44; is disappointing&#44; as evidenced by the EUROASPIRE I&#44; II and III European records and even with clear worsening in EUROASPIRE IV&#46;<a class="elsevierStyleCrossRefs" href="#bib0955"><span class="elsevierStyleSup">67&#44;116&#44;117</span></a> This last record emphasizes that in a population of patients&#44; 6 months after an acute coronary syndrome&#44; or requiring percutaneous or surgical coronary revascularization&#44;<a class="elsevierStyleCrossRef" href="#bib0955"><span class="elsevierStyleSup">67</span></a> there is persistent smoking in 16&#37;&#44; little or no physical exercise in 59&#46;9&#37;&#44; 37&#46;6&#37; are obese &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; and 58&#46;2&#37; have central obesity &#40;waist circumference &#8805;102<span class="elsevierStyleHsp" style=""></span>cm in men or &#8805;88<span class="elsevierStyleHsp" style=""></span>cm in women&#41;&#46; 42&#46;7&#37; had BP &#8805;140&#47;90<span class="elsevierStyleHsp" style=""></span>mmHg &#40;&#8805;140&#47;80 in diabetics&#41;&#46; 80&#46;5&#37; have LDL-c &#8805;70<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;&#8805;1&#46;8<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41;&#46; 26&#46;8&#37; had diabetes mellitus&#46;</p></span></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Funding</span><p id="par0395" class="elsevierStylePara elsevierViewall">Ferrer Laboratories have funded the logistics necessary for drafting this paper&#44; but in no case have they participated in the debates or decisions&#46;</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflict of interests</span><p id="par0405" class="elsevierStylePara elsevierViewall">The authors report no conflict of interest&#46;</p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Guarantees of scientific societies</span><p id="par0415" class="elsevierStylePara elsevierViewall">Spanish Society of Cardiology &#40;SEC&#41;&#46;</p><p id="par0420" class="elsevierStylePara elsevierViewall">Spanish Society of Internal Medicine &#40;SEMI&#41;&#46;</p><p id="par0425" class="elsevierStylePara elsevierViewall">Spanish Society of Family and Community Medicine &#40;SemFYC&#41;&#46;</p><p id="par0430" class="elsevierStylePara elsevierViewall">Spanish Society of General and Family Practitioners &#40;SEMG&#41;&#46;</p><p id="par0435" class="elsevierStylePara elsevierViewall">Spanish Society of Primary Care Physicians &#40;SEMERGEN&#41;&#46;</p></span></span>"
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          "titulo" => "Introduction"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0010"
              "titulo" => "Cardiovascular disease"
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            1 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Concept of adherence to therapy"
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              "identificador" => "sec0020"
              "titulo" => "Polypill"
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              "identificador" => "sec0025"
              "titulo" => "Purpose of the consensus document and field of application"
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              "titulo" => "Impact of lack of adherence on cardiovascular health"
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              "titulo" => "Adherence to therapy in secondary prevention and in patients of high&#44; or very high risk with subclinical cardiovascular disease"
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              "identificador" => "sec0050"
              "titulo" => "Actions to measure adherence to therapy"
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                  "titulo" => "In adherent patients on secondary prevention of cardiovascular disease"
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              "titulo" => "Identifying clinical situations in cardiovascular secondary prevention tributary of the administration of Polypill"
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              "titulo" => "Timing for prescribing Polypill"
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                  "titulo" => "Replacement of an angiotensin II receptor blocker by the Polypill angiotensin converting enzyme inhibitor"
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                3 => array:2 [
                  "identificador" => "sec0115"
                  "titulo" => "Replacement between statins"
                ]
              ]
            ]
            10 => array:2 [
              "identificador" => "sec0120"
              "titulo" => "Polypill limitations&#44; precautions and contraindications"
            ]
            11 => array:2 [
              "identificador" => "sec0125"
              "titulo" => "Habits and behaviors of the patient under treatment with Polypill"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0130"
          "titulo" => "Funding"
        ]
        7 => array:2 [
          "identificador" => "sec0135"
          "titulo" => "Conflict of interests"
        ]
        8 => array:2 [
          "identificador" => "sec0140"
          "titulo" => "Guarantees of scientific societies"
        ]
        9 => array:2 [
          "identificador" => "xack272671"
          "titulo" => "Acknowledgements"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-09-14"
    "fechaAceptado" => "2016-10-27"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec810532"
          "palabras" => array:6 [
            0 => "Cardiovascular disease"
            1 => "Prevention"
            2 => "Adherence"
            3 => "Recommendations"
            4 => "Combination therapy"
            5 => "Polypill"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec810531"
          "palabras" => array:6 [
            0 => "Enfermedad cardiovascular"
            1 => "Prevenci&#243;n"
            2 => "Adherencia"
            3 => "Recomendaciones"
            4 => "Tratamiento combinado"
            5 => "<span class="elsevierStyleItalic">Polypill</span>"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular disease is a chronic disorder which is usually already at an advanced stage when the first symptoms develop&#46; The fact that the initial clinical presentation can be lethal or highly incapacitating emphasizes the need for primary and secondary prevention&#46; It is estimated that the ratio of patients with good adherence to secondary prevention of cardiovascular disease is low and also decreases gradually over time&#46; The Polypill for secondary prevention of cardiovascular disease is the first fixed-dose combination therapy of salicylic acid&#44; atorvastatin and ramipril approved in Spain&#46; The purpose of this consensus document was to define and recommend&#44; through the evidence available in the literature and clinical expert opinion&#44; the impact of treatment adherence in the secondary prevention of cardiovascular disease and the use of the Polypill in daily clinical practice as part of a global strategy including adjustments in patient lifestyle&#46; A RAND&#47;UCLA methodology based on scientific evidence&#44; as well as the collective judgment and clinical expertise of an expert panel was used for this assessment&#46; As a result&#44; a final report of recommendations on the impact of the lack of adherence to treatment of secondary prevention of cardiovascular disease and the effect of using a Polypill in adherence of patients was produced&#46; The recommendations included in this document have been addressed to all those specialists&#44; cardiologists&#44; internists and primary care physicians with competence in prescribing and monitoring patients with high and very high cardiovascular risks&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La enfermedad cardiovascular suele estar en fase avanzada cuando aparecen los primeros s&#237;ntomas&#46; El hecho de que la presentaci&#243;n cl&#237;nica inicial pueda ser letal o altamente incapacitante enfatiza la necesidad de la prevenci&#243;n primaria y secundaria&#46; Se estima que la proporci&#243;n de pacientes con buena adherencia en prevenci&#243;n secundaria de la enfermedad cardiovascular es baja y disminuye progresivamente en el tiempo&#46; La <span class="elsevierStyleItalic">Polypill</span> para la prevenci&#243;n cardiovascular secundaria es el primer tratamiento combinado en dosis fija de &#225;cido acetilsalic&#237;lico&#44; atorvastatina y ramipril aprobada en Espa&#241;a&#46; El prop&#243;sito de este documento de consenso fue definir y recomendar&#44; a trav&#233;s de la evidencia en la literatura y la opini&#243;n cl&#237;nica de expertos&#44; el impacto de la adherencia al tratamiento de prevenci&#243;n cardiovascular secundaria y el uso en la pr&#225;ctica cl&#237;nica de la <span class="elsevierStyleItalic">Polypill</span> integrado en una estrategia global que incluye modificaciones en el estilo de vida&#46; Para la realizaci&#243;n de este consenso se ha utilizado la metodolog&#237;a RAND&#47;UCLA que est&#225; basada en la evidencia cient&#237;fica y en el juicio colectivo y experiencia cl&#237;nica de un panel de expertos&#46; Como resultado se ha elaborado un informe final de recomendaciones sobre el impacto de la falta de adherencia al tratamiento de la prevenci&#243;n cardiovascular secundaria y el efecto del uso de una <span class="elsevierStyleItalic">Polypill</span> en la adherencia terap&#233;utica de los pacientes&#46; Las recomendaciones de este documento se orientan a todos aquellos especialistas&#44; cardi&#243;logos&#44; m&#233;dicos internistas y m&#233;dicos de atenci&#243;n primaria con competencia en la prescripci&#243;n y seguimiento de los pacientes de alto y muy alto riesgo cardiovascular y que requieran prevenci&#243;n secundaria&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0055">Please cite this article as&#58; Gonz&#225;lez-Juanatey JR&#44; Mostaza JM&#44; Lobos JM&#44; Abarca B&#44; Llisterri JL&#44; Baron-Esquivias G&#44; et al&#46; Documento de consenso del uso cl&#237;nico de la <span class="elsevierStyleItalic">Polypill</span> en la prevenci&#243;n secundaria del riesgo cardiovascular&#46; Med Clin &#40;Barc&#41;&#46; 2017&#59;148&#58;139&#46;e1&#8211;139&#46;e15&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0060">The authors state that they have contributed to the critical revision of the intellectual content&#44; the development of the consensus document&#44; the preparation of the article and the approval of this final version&#46;</p>"
      ]
    ]
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        "fuente" => "Source&#58; <span class="elsevierStyleItalic">Scottish Intercollegiate Guidelines Network</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">26</span></a>"
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                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Levels of scientific evidence</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High quality meta-analysis&#44; systematic reviews of clinical trials or high-quality clinical trials with very little risk of bias&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Well-conducted meta-analysis&#44; systematic reviews of clinical trials or well-conducted clinical trials with low risk of bias&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Meta-analysis&#44; systematic reviews of clinical trials or clinical trials with high risk of bias&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High quality systematic reviews of cohort or case-control studies&#46; Cohort or case-control studies with very low risk of bias and moderate probability of causal relationship&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Well-conducted cohort or case-control studies with low risk of bias and moderate probability of causal relationship&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cohort or case-control studies with high risk of bias and significant risk of no causal relationship&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Non-analytical studies such as case reports and case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Expert Reviews&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Degrees of recommendation</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">At least one meta-analysis&#44; systematic review or clinical trial classified as 1&#43; and directly applicable to the target population of the guideline&#59; Or a number of scientific evidence consisting of studies classified as 1&#43; and very consistent with each other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A number of scientific evidence consisting of studies classified as 2&#43;&#43;&#44; directly applicable to the target population of the guideline and very consistent with each other&#59; Or scientific evidence extrapolated from studies classified as 1&#43;&#43; or 1&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A number of scientific evidence consisting of studies classified as 2&#43;&#43;&#44; directly applicable to the target population of the guideline and very consistent with each other&#59; Or scientific evidence extrapolated from studies classified as 2&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Scientific evidence of level 3 or 4&#59; or scientific evidence extrapolated fromstudies rated as 2&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Good clinical practice</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Recommended practice&#44; based on clinical experience and consensus by panel of experts&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Levels of evidence and degrees of recommendation &#40;SIGN&#41;&#46;</p>"
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      1 => array:9 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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        "fuente" => "Source&#58; <span class="elsevierStyleItalic">Oxford Center for Evidence-Based Medicine</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">27</span></a>"
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            "identificador" => "at2"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Levels of scientific evidence</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Systematic review with homogeneity of <span class="elsevierStyleItalic">level 1</span> studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Level 1</span> studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Level 2</span> studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Systematic review of <span class="elsevierStyleItalic">level 2</span> studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Level 3</span> studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Systematic review of <span class="elsevierStyleItalic">level 3</span> studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleSmallCaps">IV</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Consensus&#44; opinions from panel of experts with no explicit critical assessment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Level 1</span> studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">They meet&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211; Masked comparison with a valid reference test &#40;&#8220;gold standard&#8221;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211; Adequate spectrum of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Level 2</span> studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">They present only one of these biases&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211; Non-representative population &#40;the sample does not reflect the population where the test will be applied&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211; Comparison with an inadequate reference standard &#40;&#8220;gold standard&#8221;&#41; &#40;the test to be evaluated is part of the gold standard or the test result influences the gold standard&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211; Non-masked comparison&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211; Case-control studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Level 3</span> studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">They present 2 or more of the criteria described in Level 2 studies&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Recommendation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Evidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ia or Ib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">IV</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Levels of scientific evidence and recommendations for questions on diagnosis&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A&#58; agreement&#37; y &#40;n&#41;&#59; DR&#58; degree of recommendation&#59; MEMS&#58; <span class="elsevierStyleItalic">Medication Event Monitoring Systems</span> LE&#58; level of evidence&#46;</p>"
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the determinants of the lack of therapeutic adherence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A &#40;No&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE&#47;DR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There is no &#8220;patient with a non-adherence personality&#8221;&#44; although there are predictors of non-adherence&#46; Therefore&#44; adherence must be pursued in all patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#43;&#43;&#47;B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib0655"><span class="elsevierStyleSup">7&#44;118</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1365569.png"
              ]
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the actions to measure adherence to therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A &#40;No&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE&#47;DR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Direct methods to measure adherence are not of choice in routine clinical practice<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">87&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Indirect methods are the most applicable methods in routine clinical practice&#44; keeping in mind that they overestimate the adherence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The opinion or perception of the health professional is not sufficiently valid as a method of measuring adherence<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#43;&#47;D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">45&#44;46</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Methods of measurement based on clinical interview are most useful in standard practice&#44; although they offer the limitation of poor agreement with other more valid methods &#40;such as pill counts&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">87&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib0825"><span class="elsevierStyleSup">41&#44;42&#44;48&#8211;51&#44;54</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The control of prescriptions dispensed in pharmacy&#44; through the electronic prescribing modules of the clinical history&#44; provides acceptable validity and clinical applicability&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Using more than one method of therapeutic adherence assessment provides best reliability at the expense of increasing the time spent with the patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib0895"><span class="elsevierStyleSup">55&#44;56</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The measurement of pharmacological adherence will be initiated through the personalized clinical interview method&#44; using some of the self-questionnaire tests&#46; If the patient states to be compliant&#44; but non-compliance is still suspected&#44; the method of counting tablets will be applied&#46; In cases of monitoring the non-compliance pattern&#44; counting will be performed with MEMS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&#47;B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib0825"><span class="elsevierStyleSup">41&#44;42&#44;48&#44;54</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">When a therapeutic failure occurs&#44; poor therapeutic adherence might be the cause<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">87&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Some experts believed that in some cases direct methods can be useful and provide relevant information&#46;</p> <p class="elsevierStyleNotepara" id="npar0010"><span class="elsevierStyleSup">b</span> In the opinion of some experts&#44; the perception of the health professional is not valid as a measure &#40;degree of adherence&#41;&#46; However&#44; in some cases it might be a good approach&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Some experts explained that the suspicion should be verified to rule out a poor outcome or poor treatment selection&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Recommendations on the determinants of lack of therapeutic adherence and recommendations on the actions to measure adherence&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">A&#58; agreement &#37; y &#40;n&#41;&#59; CV&#58; cardiovascular&#59; DR&#58; degree of recommendation&#59; LE&#58; level of evidence&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A &#40;No&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE&#47;DR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">10&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No specific intervention can be recommended for all patients&#46; The causes of lack of adherence should be analyzed in each case&#44; which will allow to select the appropriate strategies for each patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">86&#37; &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">11&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">With the evidence currently available it cannot be stated that a specific intervention to improve adherence is better than another&#46; Combining interventions seems to be the best strategy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">12&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A good professional-patient relationship is crucial<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> and communication should be effective&#44; since these are key elements to facilitate the understanding by the patient of their disease and treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#43;&#43;&#47;B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">7</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">13&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The therapeutic plan should be agreed upon with the patient to facilitate their involvement and involve them in their monitoring and follow-up&#46; Self-responsibility should be encouraged and family members should be involved&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&#47;B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">6&#44;58</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">14&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Any strategy should include simplification of the therapeutic schedule to improve therapeutic adherence&#44; reducing the number of daily doses and using the fixed-dose combination therapy<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&#47;A<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib0965"><span class="elsevierStyleSup">69&#8211;73&#44;81&#44;82</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">15&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Therapeutic adherence has to be evaluated periodically not making the patient feel guilty&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">16&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Every pharmacological intervention should consider strategies to reinforce adherence over time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib0895"><span class="elsevierStyleSup">55&#44;57</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">17&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Effective and economically affordable drugs should be developed to ensure adherence to the therapeutic regimen in secondary prevention of CVD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">93&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#43;&#47;C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">18&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Specific recommendations should be made specifically for less adherent populations such as&#58; elderly&#44; patients with multivascular disease&#44; cerebrovascular disease&#44; comorbidities&#44; etc&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">93&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#43;&#47;C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRef" href="#bib0810"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">It includes physicians&#44; nurses and community pharmacists&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">One expert wanted to clarify that this simplification does not only mean reducing the number of doses and introducing fixed combinations&#44; but it is also important to reduce unnecessary drugs&#46;</p> <p class="elsevierStyleNotepara" id="npar0030"><span class="elsevierStyleSup">c</span> Degree of recommendation assigned according to the evidence obtained from the references indicated as source reference&#44; discussed in this and the following section&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Recommendations on actions to optimize adherence to therapy&#46;</p>"
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        "etiqueta" => "Table 5"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ASA&#58; acetylsalicylic acid&#59; CVD&#58; cardiovascular disease&#59; HTA&#58; hypertension&#59; 95&#37; CI&#58; 95&#37; confidence interval&#59; RR&#58; relative risk&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Ref&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study design&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Results&#47;conclusions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">US&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Meta-analysis of 68 studies&#44; 4 of them on patients with hypertension<br>&#8226; Comparison of treatment in fixed-dose combinations versus conventional pharmacological regimen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Fixed-dose combination therapies <span class="elsevierStyleItalic">decreased the risk of noncompliance by 26&#37;</span> compared to the conventional schedule &#40;combined RR&#58; 0&#46;74&#44; CI 95&#37;&#58; 0&#46;69&#8211;0&#46;80&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;<br>&#8226; Fixed-dose combination therapies for HT <span class="elsevierStyleItalic">decreased the risk of medication failure by 24&#37;</span> compared to the standard regimen &#40;combined RR&#58; 0&#46;76&#44; CI 95&#37;&#58; 0&#46;71&#8211;0&#46;81&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#bib0985"><span class="elsevierStyleSup">73</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Randomized clinical trial UMPIRE<br>&#8226; 1002 patients at high risk for CVD<br>&#8226; Comparison of fixed-dose combination therapy&#58; ASA&#44; simvastatin&#44; lisinopril and a drug for hypertension &#40;atenolol or hydrochlorothiazide&#41; vs standard clinical care&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; In patients with fixed-dose combination therapy&#44; adherence improved with respect to standard clinical care &#40;86 vs 95&#41;&#46; 65&#37;&#59; RR to be adherent&#58; 1&#46;33&#44; CI 95&#37;&#58; 1&#46;26&#8211;1&#46;41&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;<br>&#8226; In the subgroup of patients with lower adherence at baseline &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>727&#41;&#44; adherence at the end of the study was <span class="elsevierStyleItalic">77</span> vs <span class="elsevierStyleItalic">23&#37;</span> &#40;RR&#58; 3&#46;35&#44; CI 95&#37;&#58; 2&#46;74&#8211;4&#46;09&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001 for interaction&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; FOCUS clinical trial with 695 randomized patients<br>&#8226; Comparison of a fixed-dose combination therapy &#40;ASA&#44; simvastatin and ramipril&#41; compared to the 3 drugs administered separately<br>&#8226; Adherence to treatment measured with Morisky Green and tablet count at 9 months of follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Patients with fixed-dose combination therapy showed better adherence compared to the group receiving the drugs seaparately&#58; <span class="elsevierStyleItalic">50&#46;8&#37; adherent patients</span> vs <span class="elsevierStyleItalic">41&#37;</span> &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;019&#59; intention to treat population&#41; and 65&#46;7 vs 55&#46;7&#37; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;012&#59; per protocol population&#41; when using the main endpoint &#40;attending the final visit with Morisky Green<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20 and high pill count &#40;80&#8211;110&#37;&#41;&#46; Adherence was also higher in this group when measured by Morisky Green alone &#40;68 vs 59&#37; of adherent patients&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;049&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><a class="elsevierStyleCrossRef" href="#bib1215"><span class="elsevierStyleSup">119</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Randomized clinical trial IMPACT<br>&#8226; 513 patients at high risk for CVD<br>&#8226; Comparison of fixed-dose combination therapy &#40;ASA&#44; simvastatin&#44; lisinopril and atenolol or hydrochlorothiazide&#41; with conventional pharmacological regimen<br>&#8226; Adherence at month 12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Adherence to the 4 recommended drugs was higher within the fixed-dose combination therapy than in patients with conventional drug regimens &#40;81 vs <span class="elsevierStyleItalic">46&#37;</span> &#40;RR&#58; 1&#46;75&#44; CI 95&#37;&#58; 1&#46;52&#8211;2&#46;03&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Results of therapeutic adherence in fixed-dose combination therapies&#46;</p>"
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      5 => array:8 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">A&#58; agreement &#37; y &#40;n&#41;&#59; CV&#58; cardiovascular&#59; DR&#58; degree of recommendation&#59; LE&#58; level of evidence&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the use of fixed-dose combination therapies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A &#40;No&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE&#47;DR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">19&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A fixed-dose combination containing the active ingredients that have demonstrated its benefits in CV prevention can improve prevention by increasing patient adherence to treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib0695"><span class="elsevierStyleSup">15&#44;23&#44;65&#8211;67&#44;119</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">20&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fixed-dose combination therapies improve therapeutic adherence mainly in secondary prevention of CVD and particularly in patients such as&#58; young&#44; elderly&#44; patients with depression&#44; patients with low economic resources&#44; who live in an urban area or who have suffered a stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&#43;&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib0655"><span class="elsevierStyleSup">7&#44;15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Recommendations on the use of fixed-dose combination therapies&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0035"
        "etiqueta" => "Table 7"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">A&#58; agreement&#37; y &#40;n&#41;&#59; DR&#58; degree of recommendation&#59; LE&#58; level of evidence&#46;</p>"
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            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="middle" scope="col" style="border-bottom: 2px solid black">Nr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="middle" scope="col" style="border-bottom: 2px solid black">Recommendations on the timing of Polypill prescription&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="middle" scope="col" style="border-bottom: 2px solid black">A &#40;No&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="middle" scope="col" style="border-bottom: 2px solid black">LE&#47;DR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">21&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Although the Polypill does not include high doses of statins and these are recommended generically after an acute episode&#44; the onset with Polypill can be evaluated at hospital admission by an acute CV event if there are predicted difficulties in the patient&#39;s adhesion&#44; in accessibility to therapy or follow-up&#46; If prescription takes place when the patient is admitted or discharged&#44; it will depend on every hospital and the hospital&#39;s possibilities<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">92&#37; &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">22&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A key timing to assess Polypill prescription is when low adherence to treatment is detected for any reason&#44; during the follow-up of a patient already distant from the acute CV episode&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">23&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Another time to assess Polypill prescription is in polypharmacy patients or patients claiming reduction&#47;simplification of their multiple treatments&#44; regardless of being or not an adherent patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">24&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In case of a patient in secondary prevention of CVD&#44; their individual treatment can be modified &#40;one&#44; 2 or 3 medications separately&#41; to Polypill as a therapeutic alternative&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;A&#41; When low therapeutic adherence or difficulty to access drugs by any circumstance is detected&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;B&#41; When polymerization needs to be reduced specifically with the express claim of the patient in this regard and particularly in the adherent patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">25&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In a patient treated with Polypill&#44; therapy should be modified to a separate and individualized treatment&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; When the therapeutic purposes of the guidelines have not been met&#44; having discarded that it is the consequence of a therapeutic noncompliance&#46; The possibility of adding the extra necessary dose of other drugs separately might be considered to meet the purposes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; When intolerance to any Polypill ingredients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; When any contraindication to any Polypill ingredients occurs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "identificador" => "tblfn0025"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0035">The experts considered it important that the hospital discharge report should indicate whether the patient is provided with Polypill&#44; at the dose that the cardiologist considers necessary&#44; regardless of being or not compliant&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Recommendations on the timing of Polypill prescription&#46;</p>"
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      7 => array:8 [
        "identificador" => "tbl0040"
        "etiqueta" => "Table 8"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">A&#58; agreement &#37; y &#40;n&#41;&#59; CVD&#58; cardiovascular disease&#59; IMT&#58; average intima thickness&#59; DR&#58; degree of recommendation&#59; LVH&#58; left ventricular hypertrophy&#59; ABI&#58; ankle-brachial index&#59; LE&#58; level of evidence&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the benefits of Polypill in patients with high or very high CVR with subclinical cardiovascular disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A &#40;No&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE&#47;DR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">26&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There is sufficient evidence to consider the use of Polypill in the following subgroups of patients for subclinical CVD&#44; as long as they do not present a high risk of hemorrhage<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypertensive patients with high cardiovascular risk&#44; defined by&#58; LVH&#44; microalbuminuria&#47;proteinuria&#44; renal failure&#44; increased pulse wave velocity&#44; increased IMT&#44; presence of vascular atheroma plaque&#44; pathological ABI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Diabetic and hypertensive patients with microalbuminuria&#47;proteinuria regardless of the presence of the remaining subclinical disease markers&#46; It might also be considered in the absence of hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "identificador" => "tblfn0030"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Some members of the panel of experts stated that the dosages and indications of the Polypill ingredients separately should be taken into consideration&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Profile of high or very high risk patients with subclinical cardiovascular disease&#46;</p>"
        ]
      ]
      8 => array:8 [
        "identificador" => "tbl0045"
        "etiqueta" => "Table 9"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">A&#58; Agreement &#37; y &#40;n&#41;&#59; ARB&#58; angiotensin II receptor blocker&#59; DR&#58; degree of recommendation&#59; ACEI&#58; Angiotensin-converting-enzyme inhibitor&#59; LE&#58; level of evidence&#46;</p>"
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on ARB replacement by the ACEI of Polypill&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A &#40;No&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE&#47;DR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">27&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ARBs can be replaced by an ACEI&#44; except in cases in which the patient previously presented any side effect with an ACE-inhibitor&#44; such as cough or angioneurotic edema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">93&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&#43;&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib1040"><span class="elsevierStyleSup">84&#8211;86&#44;105&#44;106</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1365564.png"
              ]
            ]
            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the administration of Polypill in patients taking statins other than atorvastatin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A &#40;No&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE&#47;DR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">28&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In patients taking statins other than atorvastatin&#44;<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">a</span></a> they might be replaced by Polypill&#44; as long as the LDL-C lowering power is maintained in comparable terms &#40;moderate hypocholesterolemic intensity&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">93&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRef" href="#bib1170"><span class="elsevierStyleSup">110</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">29&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In patients requiring higher therapeutic intensity than with atorvastatin 20<span class="elsevierStyleHsp" style=""></span>mg<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">a</span></a> the replacement in statins can not be recommended because the loss of hypocholesterolemic effect can be accompanied by an increased risk and lower benefit of the hypocholesterolemic treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#43;&#47;D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRef" href="#bib1175"><span class="elsevierStyleSup">111</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">30&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">It is necessary to consider an individualized therapeutic approach before a therapeutic replacement&#44; taking into account the objectives of LDL-C in terms of individual risk&#44; as advocated by the European guidelines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib1020"><span class="elsevierStyleSup">80&#44;110</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1365570.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0035"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0045">Equivalent doses of different statins for reducing LDL-c by 41&#37; as is the case of atorvastatin 20<span class="elsevierStyleHsp" style=""></span>mg&#44;<a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">108</span></a> lovastatin&#58; 80<span class="elsevierStyleHsp" style=""></span>mg pitavastatin&#58; 4<span class="elsevierStyleHsp" style=""></span>mg&#44; pravastatin 80<span class="elsevierStyleHsp" style=""></span>mg&#44; rosuvastatin&#58; 5<span class="elsevierStyleHsp" style=""></span>mg and simvastatin 40<span class="elsevierStyleHsp" style=""></span>mg&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Recommendations on replacing drugs by the Polypill ingredients&#46;</p>"
        ]
      ]
      9 => array:8 [
        "identificador" => "tbl0050"
        "etiqueta" => "Table 10"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at10"
            "detalle" => "Table 1"
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">A&#58; agreement&#37; y &#40;n&#41;&#59; ASA&#58; acetylsalicylic acid&#59; DR&#58; degree of recommendation&#59; LE&#58; level of evidence&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on the administration of Polypill&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A &#40;No&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE&#47;DR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">31&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">It is recommended that Polypill be taken as a single daily capsule&#44; preferably after a meal to decrease the potential gastrointestinal side effects of ASA<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">87&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRefs" href="#bib0940"><span class="elsevierStyleSup">64&#44;114&#44;120&#8211;124</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">32&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Polypill should be swallowed with some beverage&#46; Do not chew or crush before swallowing&#46; Do not open the capsule since the closure system guarantees the pharmacological properties of the active ingredients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#43;&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span>&#44;<a class="elsevierStyleCrossRefs" href="#bib0940"><span class="elsevierStyleSup">64&#44;114</span></a><span class="elsevierStyleItalic">Available at&#58;</span><span class="elsevierStyleInterRef" id="intr0005" href="http://www.aemps.gob.es/cima/pdfs/es/ft/72375/FT_72375.pdf">http&#58;&#47;&#47;www&#46;aemps&#46;gob&#46;es&#47;cima&#47;pdfs&#47;es&#47;ft&#47;72375&#47;FT&#95;72375&#46;pdf</span><a class="elsevierStyleCrossRefs" href="#bib1220"><span class="elsevierStyleSup">120&#8211;124</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">33&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">If you forget to take a dose&#44; take your usual dose when the next&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">34&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Taking into account the characteristics of its 3 ingredients&#44; it is not expected that the effect of Polypill significantly decreases when forgetting one intake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">93&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based on the opinion of the expert panel</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1365571.png"
              ]
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          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0040"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0050">A member of the panel of experts emphasized that drug intake should be individualized in each patient depending on their characteristics and personal circumstances&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Recommendations on the administration of Polypill&#46;</p>"
        ]
      ]
      10 => array:8 [
        "identificador" => "tbl0055"
        "etiqueta" => "Table 11"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at11"
            "detalle" => "Table 1"
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">A&#58; agreement&#37; y &#40;n&#41;&#59; DR&#58; degree of recommendation&#59; LE&#58; level of evidence&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations on lifestyle habits and behaviors in patients treated with the Polypill&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A &#40;No&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE&#47;DR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">35&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Heart-healthy lifestyle habits is&#44; together with pharmacological treatment&#44; the basis of the prevention and treatment of coronary disease&#46; The cornerstones of heart-healthy lifestyle are&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#43;&#43;&#47;B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Not using toxic substances&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Heart-healthy diet&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Regular physical exercise&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Prevent from obesity especially central obesity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Control of associated standard cardiovascular risk factors &#40;diabetes&#44; hypertension&#44; dyslipidemia&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Based upon</span><a class="elsevierStyleCrossRef" href="#bib1195"><span class="elsevierStyleSup">115</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">36&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In addition&#44; educational and cardiac rehabilitation programs are necessary to promote a healthy lifestyle&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37; &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ref&#46; source</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Based upon<a class="elsevierStyleCrossRef" href="#bib1195"><span class="elsevierStyleSup">115</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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            0 => array:3 [
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                0 => array:3 [
                  "comentario" => "937&#46;e1&#8211;937&#46;e66"
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                    0 => array:1 [
                      "titulo" => "Gu&#237;a europea sobre prevenci&#243;n de la enfermedad cardiovascular en la pr&#225;ctica cl&#237;nica &#40;versi&#243;n 2012&#41;"
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                  ]
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                      "Revista" => array:3 [
                        "tituloSerie" => "Rev Esp Cardiol"
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                    ]
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              "identificador" => "bib0630"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "European Cardiovascular Disease Statistics 2012"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
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                    0 => array:1 [
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                        "editorial" => "European Heart Network&#44; Brussels&#44; European Society of Cardiology&#44; Sophia Antipolis European Heart"
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              ]
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                    0 => array:2 [
                      "titulo" => "Nota de prensa&#58; Defunciones seg&#250;n la causa de muerte a&#241;o 2012"
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                        0 => array:2 [ …2]
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                      "Libro" => array:1 [
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                    0 => array:2 [
                      "titulo" => "Coste econ&#243;mico de las enfermedades cardiovasculares desde 2014&#8211;2020 en 6 pa&#237;ses europeos"
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                        0 => array:2 [ …2]
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                    0 => array:2 [
                      "titulo" => "Joint WHO&#47;FAO expert consultation on diet&#44; nutrition and the prevention of chronic diseases"
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                        0 => array:2 [ …2]
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                    0 => array:2 [
                      "titulo" => "Adherence to long-term therapies&#58; evidence for action"
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              "identificador" => "bib0655"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "An alarming threat to secondary prevention&#58; low compliance &#40;lifestyle&#41; and poor adherence &#40;drugs&#41;"
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                        0 => array:2 [ …2]
                      ]
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                    0 => array:1 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Variations in patients&#8217; adherence to medical recommendations&#58; a quantitative review of 50 years of research"
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                        "link" => array:1 [ …1]
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              "identificador" => "bib0665"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of placebo adherence on reducing cardiovascular mortality&#58; a meta-analysis"
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                        0 => array:2 [ …2]
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                        "paginaFinal" => "235"
                        "link" => array:1 [ …1]
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              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adherence to statin or aspirin or both in patients with established cardiovascular disease&#58; exploring healthy behaviour vs&#46; drug effects and 10-year follow-up of outcome"
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                        0 => array:2 [ …2]
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                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2125.2008.03212.x"
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                        "tituloSerie" => "Br J Clin Pharmacol"
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                        "paginaFinal" => "116"
                        "link" => array:1 [ …1]
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                        0 => array:2 [ …2]
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                    0 => array:2 [
                      "doi" => "10.1002/clc.22217"
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                         …1
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Non-compliance with digoxin in patients with heart failure and&#47;or atrial fibrillation&#58; a systematic review and meta-analysis of observational studies"
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.acvd.2012.06.004"
                      "Revista" => array:6 [ …6]
                    ]
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              ]
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            12 => array:3 [
              "identificador" => "bib0685"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Aiming at strategies for a complex problem of medical nonadherence"
                      "autores" => array:1 [ …1]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.gheart.2013.06.001"
                      "Revista" => array:6 [ …6]
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              "identificador" => "bib0690"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A polypill strategy to improve global secondary cardiovascular prevention&#58; from concept to reality"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2014.06.009"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "A polypill strategy to improve adherence&#58; results from the FOCUS project"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2014.08.021"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Medication nonfulfillment rates and reasons&#58; narrative systematic review"
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1185/03007990903550586"
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                      "titulo" => "Medication nonadherence&#58; a diagnosable and treatable medical condition"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.2013.4638"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0710"
              "etiqueta" => "18"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adherence to medication"
                      "autores" => array:1 [ …1]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra050100"
                      "Revista" => array:6 [ …6]
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              ]
            ]
            18 => array:3 [
              "identificador" => "bib0715"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A meta-analysis of the association between adherence to drug therapy and mortality"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmj.38875.675486.55"
                      "Revista" => array:5 [ …5]
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                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0720"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Self-reported medication adherence and cardiovascular events in patients with stable coronary heart disease&#58; the heart and soul study"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archinte.167.16.1798"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0725"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Use of secondary prevention drugs for cardiovascular disease in the community in high-income&#44; middle-income&#44; and low-income countries &#40;the PURE Study&#41;&#58; a prospective epidemiological survey"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(11)61215-4"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0730"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "357 e357&#8211;357 e327"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The impact of medication adherence on coronary artery disease costs and outcomes&#58; a systematic review"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [ …3]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0735"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fixed-dose combinations improve medication compliance&#58; a meta-analysis"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.amjmed.2006.08.033"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0740"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ficha t&#233;cnica de Trinomia 100<span class="elsevierStyleHsp" style=""></span>mg&#47;20<span class="elsevierStyleHsp" style=""></span>mg&#47;10<span class="elsevierStyleHsp" style=""></span>mg c&#225;psulas duras"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [ …1]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0745"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "M&#233;todos de consenso&#46; Uso adecuado de la evidencia en la toma de decisiones&#46; M&#233;todo RAND&#47;UCLA"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0750"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "Available in&#58; <span class="elsevierStyleInterRef" id="intr0015" href="http://www.sign.ac.uk/guidelines/fulltext/50/index.html">http&#58;&#47;&#47;www&#46;sign&#46;ac&#46;uk&#47;guidelines&#47;fulltext&#47;50&#47;index&#46;html</span> &#91;accessed 03&#46;05&#46;13&#93;"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "SIGN 50&#58; a guideline developers&#8217; handbook"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [ …3]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0755"
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                0 => array:3 [
                  "comentario" => "Available in&#58; <span class="elsevierStyleInterRef" id="intr0020" href="http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/">http&#58;&#47;&#47;www&#46;cebm&#46;net&#47;oxford-centre-evidence-based-medicine-levels-evidence-march-2009&#47;</span> &#91;accessed 09&#46;10&#46;14&#93;"
                  "contribucion" => array:1 [
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                    0 => array:1 [
                      "Revista" => array:4 [ …4]
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                      "titulo" => "The combined use of aspirin&#44; a statin&#44; and blood pressure-lowering agents &#40;polypill components&#41; and the risk of vascular morbidity and mortality in patients with coronary artery disease"
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                    ]
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                      "Revista" => array:6 [ …6]
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                      "titulo" => "Effects of a polypill &#40;Polycap&#41; on risk factors in middle-aged individuals without cardiovascular disease &#40;TIPS&#41;&#58; a phase <span class="elsevierStyleSmallCaps">ii</span>&#44; double-blind&#44; randomised trial"
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                      "doi" => "10.1016/S0140-6736(09)60611-5"
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                    0 => array:2 [
                      "titulo" => "Effects of a secondary prevention combination therapy with an aspirin&#44; an ACE inhibitor and a statin on 1-year mortality of patients with acute myocardial infarction treated with a beta-blocker&#46; Support for a polypill approach"
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                    0 => array:2 [
                      "titulo" => "Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD&#58; the UMPIRE randomized clinical trial"
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                      "titulo" => "Projected impact of polypill use among US adults&#58; medication use&#44; cardiovascular risk reduction&#44; and side effects"
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                    0 => array:2 [
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                  "comentario" => "Available in <span class="elsevierStyleInterRef" id="intr0025" href="http://www.revespcardiol.org/es/utilidad-un-policomprimido-cardiovascular-eneltratamiento/avance-resumen/S0300-8932(16)30217-2/">http&#58;&#47;&#47;www&#46;revespcardiol&#46;org&#47;es&#47;utilidad-un-policomprimido-cardiovascular-eneltratamiento&#47;avance-resumen&#47;S0300-8932&#40;16&#41;30217-2&#47;</span>"
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                    0 => array:1 [
                      "Revista" => array:2 [ …2]
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                      "titulo" => "2016 European Guidelines on cardiovascular disease prevention in clinical practice&#58; The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice &#40;constituted by representatives of 10 societies and by invited experts&#41;&#58; developed with the special contribution of the European Association for Cardiovascular Prevention &#38; Rehabilitation &#40;EACPR&#41;"
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                    0 => array:2 [
                      "titulo" => "2013 ESC guidelines on the management of stable coronary artery disease&#58; the Task Force on the management of stable coronary artery disease of the European Society of Cardiology"
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                    ]
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                      "doi" => "10.1093/eurheartj/eht296"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "2013 ESH&#47;ESC guidelines for the management of arterial hypertension&#58; the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension &#40;ESH&#41; and of the European Society of Cardiology &#40;ESC&#41;"
                      "autores" => array:1 [ …1]
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                0 => array:2 [
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                      "titulo" => "European Guidelines on cardiovascular disease prevention in clinical practice &#40;version 2012&#41;&#46; The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice &#40;constituted by representatives of nine societies and by invited experts&#41;"
                      "autores" => array:1 [ …1]
                    ]
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                      "doi" => "10.1093/eurheartj/ehs092"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "ESC&#47;EAS guidelines for the management of dyslipidaemias&#58; the Task Force for the management of dyslipidaemias of the European Society of Cardiology &#40;ESC&#41; and the European Atherosclerosis Society &#40;EAS&#41;"
                      "autores" => array:1 [ …1]
                    ]
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              "identificador" => "bib1025"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Prevention&#58; Polypills for cardiovascular prevention&#58; a step forward&#63;"
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                    ]
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                    0 => array:2 [
                      "doi" => "10.1038/nrcardio.2013.157"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Polypill and global cardiovascular health strategies"
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                    0 => array:2 [
                      "doi" => "10.1053/j.semtcvs.2011.05.005"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Should all patients at high cardiovascular risk receive renin&#8211;angiotensin system blockers&#63;"
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                  ]
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              "identificador" => "bib1040"
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                0 => array:2 [
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                      "autores" => array:1 [ …1]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Reappraisal of European guidelines on hypertension management&#58; A European Society of Hypertension Task Force document"
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                    ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Seventh report of the Joint National Committee on Prevention&#44; Detection&#44; Evaluation&#44; and Treatment of High Blood Pressure"
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                  ]
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                ]
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                0 => array:2 [
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                    0 => array:2 [
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                    ]
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                0 => array:2 [
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                    0 => array:1 [
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                    ]
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