Use of cardiovascular polypills for the secondary prevention of cerebrovascular disease

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Masjuan, J. Gállego, J.M. Aguilera, J.F. Arenillas, M. Castellanos, F. Díaz, J.C. Portilla, F. Purroy" "autores" => array:8 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Masjuan" "email" => array:1 [ 0 => "jmasjuan.hrc@salud.madrid.org" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Gállego" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "J.M." "apellidos" => "Aguilera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 3 => array:3 [ "nombre" => "J.F." "apellidos" => "Arenillas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 4 => array:3 [ "nombre" => "M." 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"apellidos" => "Purroy" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "i" "identificador" => "aff0045" ] ] ] ] "afiliaciones" => array:9 [ 0 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Medicina, Facultad de Medicina, Universidad de Alcalá (IRYCIS), Invictus Plus, Red Nacional de Investigación en Ictus, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Complejo Hospitalario de Navarra, Pamplona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Hospital Universitario de Nuestra Señora de Valme, Sevilla, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Hospital Clínico Universitario de Valladolid, Valladolid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Complexo Hospitalario Universitario A Coruña, Instituto de Investigación Biomédica de Coruña INIBIC, La Coruña, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Hospital General Universitario Gregorio Marañón, Madrid, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Hospital Universitario San Pedro de Alcántara, Cáceres, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Hospital Arnau de Vilanova, Lérida, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Uso de la polipíldora cardiovascular en la prevención secundaria de la enfermedad cerebrovascular" ] ] "textoCompleto" => "IntroductionIschaemic stroke is one of the leading causes of death worldwide.<a class="elsevierStyleCrossRef" href="#bib0270">1</a> According to the World Health Organization, 6.7 million people died due to ischaemic stroke in 2012.<a class="elsevierStyleCrossRef" href="#bib0275">2</a> Stroke patients are at greater risk of recurrent cerebrovascular accidents. Recurrent ischaemic stroke is also associated with increased risk of vascular dementia.Poor treatment adherence is regarded as one of the main obstacles to secondary prevention of vascular disease.<a class="elsevierStyleCrossRef" href="#bib0280">3</a> Factors involved in poor treatment adherence include the chronic and sometimes scarcely symptomatic nature of cardiovascular disease, medication copayments, complex treatment approaches, and the lack of education programmes for healthcare professionals and patients.<a class="elsevierStyleCrossRef" href="#bib0285">4</a> Poor treatment adherence increases the rate of severe cardiovascular complications, including stroke, leading to higher mortality rates, poorer quality of life in survivors, increased care burden, and greater healthcare costs associated with complications and hospital admissions.<a class="elsevierStyleCrossRef" href="#bib0290">5</a>Measures including lower medication copayments, automatic reminders, mail-order pharmacies, professional healthcare advice, and fixed-dose combination therapy have helped improve treatment adherence. Simplifying treatment schedules with fixed-dose combination therapy is a complementary strategy used in a wide range of diseases to improve treatment adherence; furthermore, this approach is favourably viewed by patients. Fixed-dose combination therapy also reduces production and distribution costs, making treatment more affordable.<a class="elsevierStyleCrossRef" href="#bib0285">4</a>The cardiovascular (CV) polypill, the first combined treatment to be approved in Europe for the secondary prevention of cardiovascular diseases, contains acetylsalicylic acid (ASA), atorvastatin, and ramipril; these 3 active ingredients have been shown to reduce mortality in patients with established vascular disease.<a class="elsevierStyleCrossRefs" href="#bib0295">6–9</a>Currently marketed polypills contain 100mg ASA, 20/40mg atorvastatin, and 2.5/5/10mg ramipril.Our study analyses the impact of the CV polypill, establishes the most and least favourable clinical situations and patient profiles for this treatment, and makes some general recommendations about polypills for the secondary prevention of stroke.Material and methodsA meeting was held between an expert panel of 8 neurologists to define the structure and content of the consensus recommendations. An external moderator participated in the structured brainstorming session, facilitating discussion, organising ideas, and promoting equal participation. It was agreed that the document should address the following topics: the implications of CV polypill use for different population groups, favourable and unfavourable clinical profiles, preferential indications, and use and management recommendations. Each neurologist drafted a different part of the consensus document based on the literature and their clinical experience. The final version was reviewed and approved by all neurologists via e-mail.ResultsImplications of cardiovascular polypill administration for cerebrovascular disease preventionThe introduction of the CV polypill as a secondary prevention measure for cerebrovascular disease has considerable implications for patients, healthcare professionals, and the healthcare system (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The main advantages for patients are simplicity of treatment for cardiovascular risk factors, and improved adherence. The complexity of a treatment regime is inversely correlated with the level of adherence.<a class="elsevierStyleCrossRef" href="#bib0315">10</a> There is solid evidence of improved treatment adherence in patients receiving fixed-dose combination therapy as compared to those taking each drug separately.<a class="elsevierStyleCrossRefs" href="#bib0320">11–13</a> This may be explained by the lower risk of errors associated with taking multiple medications, and the simplicity of the treatment. Better adherence is associated with improved management of vascular risk factors. However, although polypill monocomponents alone have been shown to have an impact on risk factors, additional evidence is needed of their ability to reduce cerebrovascular events. CV polypills optimise drug prescription and treatment management, making it easier for healthcare professionals to control vascular risk factors and allowing them to allocate more time to promoting healthy habits. Despite occasions when it is necessary to supplement the CV polypill with other drugs,<a class="elsevierStyleCrossRef" href="#bib0335">14</a> fixed-dose combination therapy is compatible with personalised secondary prevention treatment.Fixed-dose combination therapy has also been shown to be cost-effective for primary and secondary prevention.<a class="elsevierStyleCrossRefs" href="#bib0340">15,16</a> Although further research into secondary prevention is needed, we may hypothesise that improved treatment adherence reduces healthcare costs when it results in better control of clinical progression and recurrence of non-cardioembolic cerebrovascular disease.Favourable and unfavourable clinical situations for use of the cardiovascular polypill for cerebrovascular disease prevention<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> summarises the situations in which the CV polypill should and should not be used, although these consensus recommendations mainly focus on the clinical situations where patients benefit the most from this treatment.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Atherothrombotic strokeAccording to some guidelines, patients with history of atherothrombotic stroke should receive antiplatelets, statins, and antihypertensives.<a class="elsevierStyleCrossRefs" href="#bib0350">17–20</a> ASA dosed at 75-325mg/day is the antiplatelet agent of choice for both extracranial and intracranial stenoses. Patients with extracranial and intracranial stenoses (critical or otherwise), recurrent stroke, or progressive stroke may be treated with ASA (75-325mg/day), clopidogrel (75mg/day), or a combination of ASA (25mg)+extended-release dipyridamole (200mg) twice daily; this drug combination is to be preferred over ASA+clopidogrel.Statins are recommended for asymptomatic patients and should be dosed to achieve a low-density lipoprotein (LDL) cholesterol level below 100mg/dL.<a class="elsevierStyleCrossRef" href="#bib0370">21</a> In patients with atherothrombotic stroke, LDL cholesterol levels should be kept below 70mg/dL.<a class="elsevierStyleCrossRefs" href="#bib0350">17,21</a> Results from clinical trials of statins in patients with ischaemic heart disease, a meta-analysis of these trials, and the SPARCL trial of patients with atherothrombotic stroke reveal a significant reduction in stroke risk, especially in patients taking atorvastatin dosed at 80mg/day.<a class="elsevierStyleCrossRefs" href="#bib0375">22,23</a>Hypertensive treatment must be started in patients with history of hypertension or with blood pressure above 140/90mm Hg. Blood pressure should be kept within the normal range (< 140/90mm Hg); no recommendations have been made for specific drugs.<a class="elsevierStyleCrossRef" href="#bib0360">19</a>Patients with atherothrombotic stroke require life-long polymedication to reduce the associated risk of recurrence; this may lower treatment adherence. Administering CV polypills to patients requiring all 3 drugs may improve adherence, always on the condition that treatment objectives be met.Lacunar strokeArterial hypertension is the main risk factor for lacunar stroke. Correctly managing blood pressure in patients with ischaemic stroke may result in a 28% decrease in the risk of stroke recurrence.<a class="elsevierStyleCrossRef" href="#bib0385">24</a> In the SPS3 trial, lower blood pressure achieved non-significant reductions in lacunar stroke recurrence. Furthermore, angiotensin-converting enzyme inhibitors prevent the progression of cerebral microangiopathy, according to MRI studies.<a class="elsevierStyleCrossRef" href="#bib0390">25</a> Antihypertensive treatment should be started in patients with history of hypertension or with blood pressure above 140/90mm Hg. Blood pressure should be kept below 140/90mm Hg; no recommendations for specific drugs have been made.<a class="elsevierStyleCrossRef" href="#bib0360">19</a>The SPARCL trial showed that statins achieve similar benefits in patients with lacunar and with other types of stroke,<a class="elsevierStyleCrossRef" href="#bib0395">26</a> although patients with lacunar stroke rarely present large-vessel atheromatosis. Antiplatelet treatment with a single drug is recommended in patients with lacunar stroke. In the SPS3 trial, treatment with 325mg ASA plus 75mg clopidogrel did not significantly reduce the risk of stroke recurrence and increased the risk of haemorrhage and death, compared to treatment with 325mg ASA only.<a class="elsevierStyleCrossRef" href="#bib0400">27</a> Antiplatelet treatment with ASA dosed at 75-325mg is recommended in these patients.<a class="elsevierStyleCrossRef" href="#bib0405">28</a> The polypill may therefore be useful in patients with lacunar stroke requiring all 3 drugs.Cryptogenic stroke associated with cardiovascular risk factorsAnticoagulants are occasionally used in patients with cryptogenic stroke, especially those meeting diagnostic criteria for embolic stroke of undetermined source. To date, however, anticoagulant treatment has not been found to be more effective for secondary prevention of cryptogenic stroke; ASA is therefore the antiplatelet treatment of choice.Classic vascular risk factors such as arterial hypertension and dyslipidaemia must be controlled; these factors are associated with increased risk of recurrence, although the risk is lower than in other stroke subtypes. The CV polypill is therefore indicated for patients with cryptogenic stroke presenting arterial hypertension and hypercholesterolaemia.Preferential indication of the cardiovascular polypill for cerebrovascular disease preventionIn addition to the previously described clinical situations, polypill treatment is more appropriate for certain patient profiles; the polypill should be preferentially indicated in these patients. Non-adherent patients constitute the most evident example. Different studies have shown that fixed-dose combination therapy achieves better treatment adherence than free drug combinations.<a class="elsevierStyleCrossRefs" href="#bib0325">12,29–34</a> No specific profile has been established for non-adherent patients, although several predictors of poor treatment adherence have been identified<a class="elsevierStyleCrossRefs" href="#bib0440">35–38</a>: young age, old age, comorbidities, polymedication, unemployment or low income, rural setting, history of stroke, and care provided by less specialised centres. Improved adherence also results in economic savings.<a class="elsevierStyleCrossRefs" href="#bib0320">11,16</a>Management of patients with multiple vascular diseases or history of atherothrombosis is complex; the polypill is particularly beneficial in these cases. Copresence of atherothrombotic stroke and coronary or peripheral artery disease, whether symptomatic or not, is frequent in clinical practice and has a significant impact on prognosis.<a class="elsevierStyleCrossRefs" href="#bib0460">39–41</a> Furthermore, mortality due to ischaemic heart disease is elevated in patients with history of stroke, and stroke recurrence is more likely in patients with history of ischaemic heart disease. Controlling vascular risk factors and ensuring treatment adherence is therefore essential in these patients, who frequently receive multiple medications. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> describes other patient profiles benefiting from treatment with the CV polypill.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Recommendations for the use of the polypill for cerebrovascular disease preventionThe European guidelines on cardiovascular disease prevention include a section on the polypill, an essential component in the global strategy for cerebrovascular disease prevention.<a class="elsevierStyleCrossRef" href="#bib0475">42</a> According to the above considerations, and the recommendations of published guidelines, our expert panel established a series of recommendations for polypill treatment initiation and follow-up.There are several possible scenarios for starting treatment with the polypill:Switching from personalised treatment to the polypill: ASA dose does not change over the course of patient follow-up, but ramipril and atorvastatin doses do require adjustment depending on blood pressure and LDL cholesterol levels, treatment adherence, and lifestyle changes. Doses should therefore be adjusted every 3-6 months to achieve objectives set for blood pressure and LDL cholesterol level, aiming to achieve good tolerability. In patients with non-cardioembolic stroke and LDL cholesterol levels above 100mg/dL, the recommended initial dose of atorvastatin is 80mg/24h. While this dose is poorly tolerated by some patients, others may achieve the target LDL cholesterol level (< 70mg/dL) with 40mg/24h.Starting treatment with the polypill during the acute phase: polypill treatment may be started during hospitalisation if the physician anticipates poor treatment adherence or compliance, or difficulties accessing treatment.Switching from a statin other than atorvastatin or an angiotensin II receptor antagonist to thepolypill<a class="elsevierStyleCrossRef" href="#bib0440">35</a>: the statin may be substituted for the polypill provided that the latter shows similar effectiveness in lowering LDL cholesterol levels.<a class="elsevierStyleCrossRef" href="#bib0480">43</a> The angiotensin II receptor antagonist may be substituted for ramipril, except in patients with history of adverse reactions to angiotensin-converting enzyme inhibitors.<a class="elsevierStyleCrossRefs" href="#bib0485">44–48</a> It is essential to verify that the polypill achieves targets for blood pressure and LDL cholesterol.Unmedicated patients: the polypill may be administered to patients who have not been treated with the 3 polypill monocomponents separately but are being considered for this treatment, especially when poor treatment adherence is anticipated or patients have difficulties accessing treatment, and in patients for whom treatment objectives are achieved with the polypill.During follow-up, physicians should:Manage blood pressure and LDL cholesterol levels, adjusting ramipril dose or adding/discontinuing other antihypertensive drugs, increasing the dose of atorvastatin or combining the drug with ezetimibe, or discontinuing the polypill and administering its monocomponents.Evaluate tolerability: there is no evidence that the polypill causes more adverse reactions than the combination of its monocomponents, although a study comparing several polypills against placebo or one polypill monocomponent reported slightly lower tolerability for polypills.<a class="elsevierStyleCrossRef" href="#bib0510">49</a> Any adverse reaction should be managed by adjusting the dose of the drug responsible.DiscussionA wide range of polypills with different drug combinations have been approved for different diseases. Polypills are widely used to treat infectious diseases, and there is mounting evidence of their benefits for patients with cardiovascular diseases<a class="elsevierStyleCrossRefs" href="#bib0515">50,51</a>; however, much work remains to be done in the field of cardiovascular prevention. This study makes recommendations for use of the CV polypill containing ASA, atorvastatin, and ramipril for secondary prevention of cerebrovascular disease. These recommendations were made by consensus by a panel of neurologists and focus on the most appropriate patient profiles, clinical situations, and administration approaches.The benefits of the polypill involve the management of cardiovascular risk factors and improved treatment adherence. Therefore, the polypill is indicated for potentially non-adherent patients and those requiring strict follow-up of treatment objectives, such as elderly patients, polymedicated patients, patients with multiple vascular diseases, or individuals with history of atherothrombosis. The polypill is more beneficial in some clinical situations than in others; these recommendations are intended to provide an introduction to this topic.Interest in fixed-dose combination therapy has increased in recent years, probably due to the associated advantages for patients, healthcare professionals, and the healthcare system. In fact, the European Medicines Agency's Committee for Medicinal Products for Human Use recently updated its guidelines on fixed combination medicinal products; the new version is expected to come into force in October 2017.Some researchers have highlighted the potential of the CV polypill for improving secondary prevention of stroke.<a class="elsevierStyleCrossRefs" href="#bib0290">5,52,53</a> There are currently no recommendations establishing the patient profiles and clinical situations in which the polypill has the greatest benefits for cerebrovascular disease, although such recommendations do exist for CV polypill treatment for secondary prevention of cardiovascular disease.<a class="elsevierStyleCrossRef" href="#bib0290">5</a> In this context, expert opinion is particularly important; this study provides a starting point for determining which patients may benefit the most from fixed-dose combination therapy for secondary prevention of cerebrovascular accidents.This study has the limitation that it is based on expert opinion rather than on well-designed clinical trials; furthermore, no systematic review of the literature has been conducted to provide evidence for our recommendations. In any case, these recommendations were drafted based on the consensus of a panel of respected specialists with broad clinical experience in the management of these patients.FundingThis study was funded by Grupo Ferrer Internacional, S.A.Conflicts of interestAll authors received professional fees from Grupo Ferrer Internacional, S.A. for this study." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1447986" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1320752" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1447987" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1320751" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Implications of cardiovascular polypill administration for cerebrovascular disease prevention" ] 1 => array:3 [ "identificador" => "sec0025" "titulo" => "Favourable and unfavourable clinical situations for use of the cardiovascular polypill for cerebrovascular disease prevention" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Atherothrombotic stroke" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Lacunar stroke" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Cryptogenic stroke associated with cardiovascular risk factors" ] ] ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Preferential indication of the cardiovascular polypill for cerebrovascular disease prevention" ] 3 => array:2 [ "identificador" => "sec0050" "titulo" => "Recommendations for the use of the polypill for cerebrovascular disease prevention" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflicts of interest" ] 10 => array:2 [ "identificador" => "xack505784" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-06-08" "fechaAceptado" => "2017-10-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1320752" "palabras" => array:6 [ 0 => "Cerebrovascular disease" 1 => "Stroke" 2 => "Fixed-dose combination" 3 => "Medication adherence" 4 => "Secondary prevention" 5 => "Polypill" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1320751" "palabras" => array:6 [ 0 => "Enfermedad cerebrovascular" 1 => "ICTUS" 2 => "Combinación de dosis fijas" 3 => "Adherencia terapéutica" 4 => "Prevención secundaria" 5 => "Polypill" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionThere is little control of cardiovascular (CV) risk factors in secondary prevention after an ischaemic stroke, in part due to a lack of adherence to treatment. The CV polypill may contribute to proper treatment adherence, which is necessary for CV disease prevention. This study aimed to establish how and in what cases the CV polypill should be administered. MethodsA group of 8 neurologists drafted consensus recommendations using structured brainstorming and based on their experience and a literature review. ResultsThese recommendations are based on the opinion of the participating experts. The use of the CV polypill is beneficial for patients, healthcare professionals, and the health system. Its use is most appropriate for atherothrombotic stroke, lacunar stroke, stroke associated with cognitive impairment, cryptogenic stroke with CV risk factors, and silent cerebrovascular disease. It is the preferred treatment in cases of suspected poor adherence, polymedicated patients, elderly people, patients with polyvascular disease or severe atherothrombosis, young patients in active work, and patients who express a preference for the CV polypill. Administration options include switching from individual drugs to the CV polypill, starting treatment with the CV polypill in the acute phase in particular cases, use in patients receiving another statin or an angiotensin ii receptor antagonist, or de novo use if there is suspicion of poor adherence. Nevertheless, use of the CV polypill requires follow-up on the achievement of the therapeutic objectives to make dose adjustments. ConclusionsThis document is the first to establish recommendations for the use of the CV polypill in cerebrovascular disease, beyond its advantages in terms of treatment adherence." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónEl control de los factores de riesgo cardiovascular (CV) en la prevención secundaria tras un ictus isquémico es bajo, en parte debido a la falta de adherencia terapéutica. La polipíldora CV puede contribuir a la buena cumplimentación del adecuado tratamiento para la prevención cerebrovascular. El objetivo fue establecer cómo y en qué casos se debería administrar. MétodosUn grupo de 8neurólogos redactaron recomendaciones consensuadas mediante una técnica de brainstorming estructurado, basándose en su experiencia y en una revisión bibliográfica. ResultadosLos resultados atienden a la opinión de los expertos. El uso de la polipíldora CV tiene ventajas para pacientes, profesionales sanitarios y para el sistema de salud. Las situaciones clínicas más adecuadas para su uso son el ictus aterotrombótico, el lacunar, el asociado a deterioro cognitivo, el criptogénico con factores de riesgo CV y la enfermedad cerebrovascular silente. Su uso preferente incluye la sospecha de mal cumplimiento, a los pacientes polimedicados, ancianos, polivasculares o con alta carga aterotrombótica, jóvenes activos laboralmente y pacientes con preferencias por la polipíldora CV. Las opciones de administración incluyen el paso de fármacos individuales a la polipíldora CV, el inicio directo desde la fase aguda en casos particulares, a los pacientes con otra estatina o con un antagonista del receptor de la angiotensina ii, o de novo si hubiera sospecha de mala adherencia. No obstante, su uso implica realizar seguimiento del cumplimiento de los objetivos terapéuticos para ajustar la dosis. ConclusionesEste documento es el primero en establecer recomendaciones de uso de la polipíldora CV en enfermedad cerebrovascular, aparte de sus ventajas sobre la adherencia." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Masjuan J, Gállego J, Aguilera JM, Arenillas JF, Castellanos M, Díaz F, et al. Uso de la polipíldora cardiovascular en la prevención secundaria de la enfermedad cerebrovascular. Neurología. 2021;36:1–8." ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "CVRF: cardiovascular risk factors." "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Healthcare professional \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Healthcare system \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Advantages</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Better control of CVRF, which improves treatment adherence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Easier monitoring of treatment adherence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Probable reduction in monetary costs \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Easier administration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Easier to prescribe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Easier to prescribe \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minimises errors in taking the medicine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">More time-efficient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In line with healthcare protocols \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Better control of vascular risk factors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Strengthens the idea of “global disease” \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Better coordination and continuity of care between primary and specialised care \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduces the perception of stroke as a chronic disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In line with the Treatment Adherence Plan designed by Farmaindustria<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Easier dosage planning \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Better management of chronic patients \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Disadvantages</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risk of trivialising treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reluctance to changing treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Skipping a dose has worse consequences \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lack of flexibility in components and dosage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment may need to be supplemented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not suitable for all patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2490271.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "National trade association for Spanish-based pharmaceutical companies." ] ] ] "descripcion" => array:1 [ "en" => "Implications of the use of cardiovascular polypills for cerebrovascular disease prevention." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "CVRF: cardiovascular risk factors." "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Recommended \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Not recommended \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Atherothrombotic stroke \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardioembolic stroke \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lacunar stroke \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients with stroke but not presenting arterial hypertension or dyslipidaemia<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cryptogenic stroke associated with CVRF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intolerance to or contraindications for any of the polypill monocomponents \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2490269.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "Polypill administration may be considered if atherothrombotic or lacunar stroke are suspected. These patients should be evaluated on a case-by-case basis." ] ] ] "descripcion" => array:1 [ "en" => "Favourable and unfavourable clinical situations for use of cardiovascular polypills for cerebrovascular disease prevention." ] ] 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: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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient profile \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Suspicion of poor treatment adherence \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Polymedication \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Elderly patients \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multiple vascular diseases or history of atherothrombosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Young patients who are active workers or need to travel frequently \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patient preference for CV polypill \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2490270.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Patients profiles with preferential indication for cardiovascular polypills for cerebrovascular disease prevention." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:53 [ 0 => array:3 [ "identificador" => "bib0270" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Instituto Nacional de Estadística 2012. 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Uso de la polipíldora cardiovascular en la prevención secundaria de la enfermedad cerebrovascular

J. Masjuana,b,

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jmasjuan.hrc@salud.madrid.org

Corresponding author.

, J. Gállegoc, J.M. Aguilerad, J.F. Arenillase, M. Castellanosf, F. Díazg, J.C. Portillah, F. Purroyi

a Servicio de Neurología, Hospital Universitario Ramón y Cajal, Madrid, Spain

b Departamento de Medicina, Facultad de Medicina, Universidad de Alcalá (IRYCIS), Invictus Plus, Red Nacional de Investigación en Ictus, Madrid, Spain

c Complejo Hospitalario de Navarra, Pamplona, Spain

d Hospital Universitario de Nuestra Señora de Valme, Sevilla, Spain

e Hospital Clínico Universitario de Valladolid, Valladolid, Spain

f Complexo Hospitalario Universitario A Coruña, Instituto de Investigación Biomédica de Coruña INIBIC, La Coruña, Spain

g Hospital General Universitario Gregorio Marañón, Madrid, Spain

h Hospital Universitario San Pedro de Alcántara, Cáceres, Spain

i Hospital Arnau de Vilanova, Lérida, Spain

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        "titulo" => "Uso de la polip&#237;ldora cardiovascular en la prevenci&#243;n secundaria de la enfermedad cerebrovascular"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Ischaemic stroke is one of the leading causes of death worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">1</span></a> According to the World Health Organization&#44; 6&#46;7 million people died due to ischaemic stroke in 2012&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">2</span></a> Stroke patients are at greater risk of recurrent cerebrovascular accidents&#46; Recurrent ischaemic stroke is also associated with increased risk of vascular dementia&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Poor treatment adherence is regarded as one of the main obstacles to secondary prevention of vascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">3</span></a> Factors involved in poor treatment adherence include the chronic and sometimes scarcely symptomatic nature of cardiovascular disease&#44; medication copayments&#44; complex treatment approaches&#44; and the lack of education programmes for healthcare professionals and patients&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">4</span></a> Poor treatment adherence increases the rate of severe cardiovascular complications&#44; including stroke&#44; leading to higher mortality rates&#44; poorer quality of life in survivors&#44; increased care burden&#44; and greater healthcare costs associated with complications and hospital admissions&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Measures including lower medication copayments&#44; automatic reminders&#44; mail-order pharmacies&#44; professional healthcare advice&#44; and fixed-dose combination therapy have helped improve treatment adherence&#46; Simplifying treatment schedules with fixed-dose combination therapy is a complementary strategy used in a wide range of diseases to improve treatment adherence&#59; furthermore&#44; this approach is favourably viewed by patients&#46; Fixed-dose combination therapy also reduces production and distribution costs&#44; making treatment more affordable&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The cardiovascular &#40;CV&#41; polypill&#44; the first combined treatment to be approved in Europe for the secondary prevention of cardiovascular diseases&#44; contains acetylsalicylic acid &#40;ASA&#41;&#44; atorvastatin&#44; and ramipril&#59; these 3 active ingredients have been shown to reduce mortality in patients with established vascular disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">6&#8211;9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Currently marketed polypills contain 100<span class="elsevierStyleHsp" style=""></span>mg ASA&#44; 20&#47;40<span class="elsevierStyleHsp" style=""></span>mg atorvastatin&#44; and 2&#46;5&#47;5&#47;10<span class="elsevierStyleHsp" style=""></span>mg ramipril&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Our study analyses the impact of the CV polypill&#44; establishes the most and least favourable clinical situations and patient profiles for this treatment&#44; and makes some general recommendations about polypills for the secondary prevention of stroke&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">A meeting was held between an expert panel of 8 neurologists to define the structure and content of the consensus recommendations&#46; An external moderator participated in the structured brainstorming session&#44; facilitating discussion&#44; organising ideas&#44; and promoting equal participation&#46; It was agreed that the document should address the following topics&#58; the implications of CV polypill use for different population groups&#44; favourable and unfavourable clinical profiles&#44; preferential indications&#44; and use and management recommendations&#46; Each neurologist drafted a different part of the consensus document based on the literature and their clinical experience&#46; The final version was reviewed and approved by all neurologists <span class="elsevierStyleItalic">via</span> e-mail&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Implications of cardiovascular polypill administration for cerebrovascular disease prevention</span><p id="par0040" class="elsevierStylePara elsevierViewall">The introduction of the CV polypill as a secondary prevention measure for cerebrovascular disease has considerable implications for patients&#44; healthcare professionals&#44; and the healthcare system &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The main advantages for patients are simplicity of treatment for cardiovascular risk factors&#44; and improved adherence&#46; The complexity of a treatment regime is inversely correlated with the level of adherence&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">10</span></a> There is solid evidence of improved treatment adherence in patients receiving fixed-dose combination therapy as compared to those taking each drug separately&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">11&#8211;13</span></a> This may be explained by the lower risk of errors associated with taking multiple medications&#44; and the simplicity of the treatment&#46; Better adherence is associated with improved management of vascular risk factors&#46; However&#44; although polypill monocomponents alone have been shown to have an impact on risk factors&#44; additional evidence is needed of their ability to reduce cerebrovascular events&#46; CV polypills optimise drug prescription and treatment management&#44; making it easier for healthcare professionals to control vascular risk factors and allowing them to allocate more time to promoting healthy habits&#46; Despite occasions when it is necessary to supplement the CV polypill with other drugs&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">14</span></a> fixed-dose combination therapy is compatible with personalised secondary prevention treatment&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Fixed-dose combination therapy has also been shown to be cost-effective for primary and secondary prevention&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">15&#44;16</span></a> Although further research into secondary prevention is needed&#44; we may hypothesise that improved treatment adherence reduces healthcare costs when it results in better control of clinical progression and recurrence of non-cardioembolic cerebrovascular disease&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Favourable and unfavourable clinical situations for use of the cardiovascular polypill for cerebrovascular disease prevention</span><p id="par0055" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> summarises the situations in which the CV polypill should and should not be used&#44; although these consensus recommendations mainly focus on the clinical situations where patients benefit the most from this treatment&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Atherothrombotic stroke</span><p id="par0060" class="elsevierStylePara elsevierViewall">According to some guidelines&#44; patients with history of atherothrombotic stroke should receive antiplatelets&#44; statins&#44; and antihypertensives&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">17&#8211;20</span></a> ASA dosed at 75-325<span class="elsevierStyleHsp" style=""></span>mg&#47;day is the antiplatelet agent of choice for both extracranial and intracranial stenoses&#46; Patients with extracranial and intracranial stenoses &#40;critical or otherwise&#41;&#44; recurrent stroke&#44; or progressive stroke may be treated with ASA &#40;75-325<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#44; clopidogrel &#40;75<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#44; or a combination of ASA &#40;25<span class="elsevierStyleHsp" style=""></span>mg&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>extended-release dipyridamole &#40;200<span class="elsevierStyleHsp" style=""></span>mg&#41; twice daily&#59; this drug combination is to be preferred over ASA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>clopidogrel&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Statins are recommended for asymptomatic patients and should be dosed to achieve a low-density lipoprotein &#40;LDL&#41; cholesterol level below 100<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">21</span></a> In patients with atherothrombotic stroke&#44; LDL cholesterol levels should be kept below 70<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">17&#44;21</span></a> Results from clinical trials of statins in patients with ischaemic heart disease&#44; a meta-analysis of these trials&#44; and the SPARCL trial of patients with atherothrombotic stroke reveal a significant reduction in stroke risk&#44; especially in patients taking atorvastatin dosed at 80<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Hypertensive treatment must be started in patients with history of hypertension or with blood pressure above 140&#47;90<span class="elsevierStyleHsp" style=""></span>mm Hg&#46; Blood pressure should be kept within the normal range &#40;&#60; 140&#47;90<span class="elsevierStyleHsp" style=""></span>mm Hg&#41;&#59; no recommendations have been made for specific drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">19</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Patients with atherothrombotic stroke require life-long polymedication to reduce the associated risk of recurrence&#59; this may lower treatment adherence&#46; Administering CV polypills to patients requiring all 3 drugs may improve adherence&#44; always on the condition that treatment objectives be met&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Lacunar stroke</span><p id="par0080" class="elsevierStylePara elsevierViewall">Arterial hypertension is the main risk factor for lacunar stroke&#46; Correctly managing blood pressure in patients with ischaemic stroke may result in a 28&#37; decrease in the risk of stroke recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">24</span></a> In the SPS3 trial&#44; lower blood pressure achieved non-significant reductions in lacunar stroke recurrence&#46; Furthermore&#44; angiotensin-converting enzyme inhibitors prevent the progression of cerebral microangiopathy&#44; according to MRI studies&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">25</span></a> Antihypertensive treatment should be started in patients with history of hypertension or with blood pressure above 140&#47;90<span class="elsevierStyleHsp" style=""></span>mm Hg&#46; Blood pressure should be kept below 140&#47;90<span class="elsevierStyleHsp" style=""></span>mm Hg&#59; no recommendations for specific drugs have been made&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">19</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The SPARCL trial showed that statins achieve similar benefits in patients with lacunar and with other types of stroke&#44;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">26</span></a> although patients with lacunar stroke rarely present large-vessel atheromatosis&#46; Antiplatelet treatment with a single drug is recommended in patients with lacunar stroke&#46; In the SPS3 trial&#44; treatment with 325<span class="elsevierStyleHsp" style=""></span>mg ASA plus 75<span class="elsevierStyleHsp" style=""></span>mg clopidogrel did not significantly reduce the risk of stroke recurrence and increased the risk of haemorrhage and death&#44; compared to treatment with 325<span class="elsevierStyleHsp" style=""></span>mg ASA only&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">27</span></a> Antiplatelet treatment with ASA dosed at 75-325<span class="elsevierStyleHsp" style=""></span>mg is recommended in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">28</span></a> The polypill may therefore be useful in patients with lacunar stroke requiring all 3 drugs&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Cryptogenic stroke associated with cardiovascular risk factors</span><p id="par0090" class="elsevierStylePara elsevierViewall">Anticoagulants are occasionally used in patients with cryptogenic stroke&#44; especially those meeting diagnostic criteria for embolic stroke of undetermined source&#46; To date&#44; however&#44; anticoagulant treatment has not been found to be more effective for secondary prevention of cryptogenic stroke&#59; ASA is therefore the antiplatelet treatment of choice&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Classic vascular risk factors such as arterial hypertension and dyslipidaemia must be controlled&#59; these factors are associated with increased risk of recurrence&#44; although the risk is lower than in other stroke subtypes&#46; The CV polypill is therefore indicated for patients with cryptogenic stroke presenting arterial hypertension and hypercholesterolaemia&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Preferential indication of the cardiovascular polypill for cerebrovascular disease prevention</span><p id="par0100" class="elsevierStylePara elsevierViewall">In addition to the previously described clinical situations&#44; polypill treatment is more appropriate for certain patient profiles&#59; the polypill should be preferentially indicated in these patients&#46; Non-adherent patients constitute the most evident example&#46; Different studies have shown that fixed-dose combination therapy achieves better treatment adherence than free drug combinations&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">12&#44;29&#8211;34</span></a> No specific profile has been established for non-adherent patients&#44; although several predictors of poor treatment adherence have been identified<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">35&#8211;38</span></a>&#58; young age&#44; old age&#44; comorbidities&#44; polymedication&#44; unemployment or low income&#44; rural setting&#44; history of stroke&#44; and care provided by less specialised centres&#46; Improved adherence also results in economic savings&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">11&#44;16</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Management of patients with multiple vascular diseases or history of atherothrombosis is complex&#59; the polypill is particularly beneficial in these cases&#46; Copresence of atherothrombotic stroke and coronary or peripheral artery disease&#44; whether symptomatic or not&#44; is frequent in clinical practice and has a significant impact on prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">39&#8211;41</span></a> Furthermore&#44; mortality due to ischaemic heart disease is elevated in patients with history of stroke&#44; and stroke recurrence is more likely in patients with history of ischaemic heart disease&#46; Controlling vascular risk factors and ensuring treatment adherence is therefore essential in these patients&#44; who frequently receive multiple medications&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> describes other patient profiles benefiting from treatment with the CV polypill&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Recommendations for the use of the polypill for cerebrovascular disease prevention</span><p id="par0110" class="elsevierStylePara elsevierViewall">The European guidelines on cardiovascular disease prevention include a section on the polypill&#44; an essential component in the global strategy for cerebrovascular disease prevention&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">42</span></a> According to the above considerations&#44; and the recommendations of published guidelines&#44; our expert panel established a series of recommendations for polypill treatment initiation and follow-up&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">There are several possible scenarios for starting treatment with the polypill&#58;</p><p id="par0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Switching from personalised treatment to the polypill</span>&#58; ASA dose does not change over the course of patient follow-up&#44; but ramipril and atorvastatin doses do require adjustment depending on blood pressure and LDL cholesterol levels&#44; treatment adherence&#44; and lifestyle changes&#46; Doses should therefore be adjusted every 3-6 months to achieve objectives set for blood pressure and LDL cholesterol level&#44; aiming to achieve good tolerability&#46; In patients with non-cardioembolic stroke and LDL cholesterol levels above 100<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; the recommended initial dose of atorvastatin is 80<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&#46; While this dose is poorly tolerated by some patients&#44; others may achieve the target LDL cholesterol level &#40;&#60; 70<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; with 40<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Starting treatment with the polypill during the acute phase</span>&#58; polypill treatment may be started during hospitalisation if the physician anticipates poor treatment adherence or compliance&#44; or difficulties accessing treatment&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Switching from a statin other than atorvastatin or an angiotensin II receptor antagonist to the</span><span class="elsevierStyleItalic">polypill</span><a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">35</span></a>&#58; the statin may be substituted for the polypill provided that the latter shows similar effectiveness in lowering LDL cholesterol levels&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">43</span></a> The angiotensin II receptor antagonist may be substituted for ramipril&#44; except in patients with history of adverse reactions to angiotensin-converting enzyme inhibitors&#46;<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">44&#8211;48</span></a> It is essential to verify that the polypill achieves targets for blood pressure and LDL cholesterol&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Unmedicated patients</span>&#58; the polypill may be administered to patients who have not been treated with the 3 polypill monocomponents separately but are being considered for this treatment&#44; especially when poor treatment adherence is anticipated or patients have difficulties accessing treatment&#44; and in patients for whom treatment objectives are achieved with the polypill&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">During follow-up&#44; physicians should&#58;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Manage blood pressure and LDL cholesterol levels&#44; adjusting ramipril dose or adding&#47;discontinuing other antihypertensive drugs&#44; increasing the dose of atorvastatin or combining the drug with ezetimibe&#44; or discontinuing the polypill and administering its monocomponents&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Evaluate tolerability&#58; there is no evidence that the polypill causes more adverse reactions than the combination of its monocomponents&#44; although a study comparing several polypills against placebo or one polypill monocomponent reported slightly lower tolerability for polypills&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">49</span></a> Any adverse reaction should be managed by adjusting the dose of the drug responsible&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">A wide range of polypills with different drug combinations have been approved for different diseases&#46; Polypills are widely used to treat infectious diseases&#44; and there is mounting evidence of their benefits for patients with cardiovascular diseases<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">50&#44;51</span></a>&#59; however&#44; much work remains to be done in the field of cardiovascular prevention&#46; This study makes recommendations for use of the CV polypill containing ASA&#44; atorvastatin&#44; and ramipril for secondary prevention of cerebrovascular disease&#46; These recommendations were made by consensus by a panel of neurologists and focus on the most appropriate patient profiles&#44; clinical situations&#44; and administration approaches&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The benefits of the polypill involve the management of cardiovascular risk factors and improved treatment adherence&#46; Therefore&#44; the polypill is indicated for potentially non-adherent patients and those requiring strict follow-up of treatment objectives&#44; such as elderly patients&#44; polymedicated patients&#44; patients with multiple vascular diseases&#44; or individuals with history of atherothrombosis&#46; The polypill is more beneficial in some clinical situations than in others&#59; these recommendations are intended to provide an introduction to this topic&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Interest in fixed-dose combination therapy has increased in recent years&#44; probably due to the associated advantages for patients&#44; healthcare professionals&#44; and the healthcare system&#46; In fact&#44; the European Medicines Agency&#39;s Committee for Medicinal Products for Human Use recently updated its guidelines on fixed combination medicinal products&#59; the new version is expected to come into force in October 2017&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Some researchers have highlighted the potential of the CV polypill for improving secondary prevention of stroke&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">5&#44;52&#44;53</span></a> There are currently no recommendations establishing the patient profiles and clinical situations in which the polypill has the greatest benefits for cerebrovascular disease&#44; although such recommendations do exist for CV polypill treatment for secondary prevention of cardiovascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">5</span></a> In this context&#44; expert opinion is particularly important&#59; this study provides a starting point for determining which patients may benefit the most from fixed-dose combination therapy for secondary prevention of cerebrovascular accidents&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">This study has the limitation that it is based on expert opinion rather than on well-designed clinical trials&#59; furthermore&#44; no systematic review of the literature has been conducted to provide evidence for our recommendations&#46; In any case&#44; these recommendations were drafted based on the consensus of a panel of respected specialists with broad clinical experience in the management of these patients&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Funding</span><p id="par0185" class="elsevierStylePara elsevierViewall">This study was funded by <span class="elsevierStyleGrantSponsor" id="gs1">Grupo Ferrer Internacional&#44; S&#46;A</span>&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of interest</span><p id="par0190" class="elsevierStylePara elsevierViewall">All authors received professional fees from Grupo Ferrer Internacional&#44; S&#46;A&#46; for this study&#46;</p></span></span>"
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              "titulo" => "Implications of cardiovascular polypill administration for cerebrovascular disease prevention"
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              "titulo" => "Favourable and unfavourable clinical situations for use of the cardiovascular polypill for cerebrovascular disease prevention"
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                  "identificador" => "sec0030"
                  "titulo" => "Atherothrombotic stroke"
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                  "titulo" => "Lacunar stroke"
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                2 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Cryptogenic stroke associated with cardiovascular risk factors"
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              "identificador" => "sec0045"
              "titulo" => "Preferential indication of the cardiovascular polypill for cerebrovascular disease prevention"
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              "titulo" => "Recommendations for the use of the polypill for cerebrovascular disease prevention"
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    "fechaRecibido" => "2017-06-08"
    "fechaAceptado" => "2017-10-03"
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          "clase" => "keyword"
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          "palabras" => array:6 [
            0 => "Cerebrovascular disease"
            1 => "Stroke"
            2 => "Fixed-dose combination"
            3 => "Medication adherence"
            4 => "Secondary prevention"
            5 => "Polypill"
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            0 => "Enfermedad cerebrovascular"
            1 => "ICTUS"
            2 => "Combinaci&#243;n de dosis fijas"
            3 => "Adherencia terap&#233;utica"
            4 => "Prevenci&#243;n secundaria"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">There is little control of cardiovascular &#40;CV&#41; risk factors in secondary prevention after an ischaemic stroke&#44; in part due to a lack of adherence to treatment&#46; The CV polypill may contribute to proper treatment adherence&#44; which is necessary for CV disease prevention&#46; This study aimed to establish how and in what cases the CV polypill should be administered&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A group of 8 neurologists drafted consensus recommendations using structured brainstorming and based on their experience and a literature review&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">These recommendations are based on the opinion of the participating experts&#46; The use of the CV polypill is beneficial for patients&#44; healthcare professionals&#44; and the health system&#46; Its use is most appropriate for atherothrombotic stroke&#44; lacunar stroke&#44; stroke associated with cognitive impairment&#44; cryptogenic stroke with CV risk factors&#44; and silent cerebrovascular disease&#46; It is the preferred treatment in cases of suspected poor adherence&#44; polymedicated patients&#44; elderly people&#44; patients with polyvascular disease or severe atherothrombosis&#44; young patients in active work&#44; and patients who express a preference for the CV polypill&#46; Administration options include switching from individual drugs to the CV polypill&#44; starting treatment with the CV polypill in the acute phase in particular cases&#44; use in patients receiving another statin or an angiotensin <span class="elsevierStyleSmallCaps">ii</span> receptor antagonist&#44; or <span class="elsevierStyleItalic">de novo</span> use if there is suspicion of poor adherence&#46; Nevertheless&#44; use of the CV polypill requires follow-up on the achievement of the therapeutic objectives to make dose adjustments&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This document is the first to establish recommendations for the use of the CV polypill in cerebrovascular disease&#44; beyond its advantages in terms of treatment adherence&#46;</p></span>"
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            "identificador" => "abst0005"
            "titulo" => "Introduction"
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            "titulo" => "Methods"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El control de los factores de riesgo cardiovascular &#40;<span class="elsevierStyleSmallCaps">C</span>V&#41; en la prevenci&#243;n secundaria tras un ictus isqu&#233;mico es bajo&#44; en parte debido a la falta de adherencia terap&#233;utica&#46; La polip&#237;ldora CV puede contribuir a la buena cumplimentaci&#243;n del adecuado tratamiento para la prevenci&#243;n cerebrovascular&#46; El objetivo fue establecer c&#243;mo y en qu&#233; casos se deber&#237;a administrar&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Un grupo de 8<span class="elsevierStyleHsp" style=""></span>neur&#243;logos redactaron recomendaciones consensuadas mediante una t&#233;cnica de <span class="elsevierStyleItalic">brainstorming</span> estructurado&#44; bas&#225;ndose en su experiencia y en una revisi&#243;n bibliogr&#225;fica&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los resultados atienden a la opini&#243;n de los expertos&#46; El uso de la polip&#237;ldora CV tiene ventajas para pacientes&#44; profesionales sanitarios y para el sistema de salud&#46; Las situaciones cl&#237;nicas m&#225;s adecuadas para su uso son el ictus aterotromb&#243;tico&#44; el lacunar&#44; el asociado a deterioro cognitivo&#44; el criptog&#233;nico con factores de riesgo CV y la enfermedad cerebrovascular silente&#46; Su uso preferente incluye la sospecha de mal cumplimiento&#44; a los pacientes polimedicados&#44; ancianos&#44; polivasculares o con alta carga aterotromb&#243;tica&#44; j&#243;venes activos laboralmente y pacientes con preferencias por la polip&#237;ldora CV&#46; Las opciones de administraci&#243;n incluyen el paso de f&#225;rmacos individuales a la polip&#237;ldora CV&#44; el inicio directo desde la fase aguda en casos particulares&#44; a los pacientes con otra estatina o con un antagonista del receptor de la angiotensina <span class="elsevierStyleSmallCaps">ii</span>&#44; o <span class="elsevierStyleItalic">de novo</span> si hubiera sospecha de mala adherencia&#46; No obstante&#44; su uso implica realizar seguimiento del cumplimiento de los objetivos terap&#233;uticos para ajustar la dosis&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este documento es el primero en establecer recomendaciones de uso de la polip&#237;ldora CV en enfermedad cerebrovascular&#44; aparte de sus ventajas sobre la adherencia&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Masjuan J&#44; G&#225;llego J&#44; Aguilera JM&#44; Arenillas JF&#44; Castellanos M&#44; D&#237;az F&#44; et al&#46; Uso de la polip&#237;ldora cardiovascular en la prevenci&#243;n secundaria de la enfermedad cerebrovascular&#46; Neurolog&#237;a&#46; 2021&#59;36&#58;1&#8211;8&#46;</p>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">CVRF&#58; cardiovascular risk factors&#46;</p>"
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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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Healthcare professional&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Healthcare system&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " rowspan="6" align="left" valign="\n
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                  \t\t\t\t">Advantages</td><td class="td" title="\n
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                  \t\t\t\t">Better control of CVRF&#44; which improves treatment adherence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Easier monitoring of treatment adherence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Probable reduction in monetary costs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Easier administration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Easier to prescribe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Easier to prescribe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Minimises errors in taking the medicine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">More time-efficient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">In line with healthcare protocols&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Better control of vascular risk factors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Strengthens the idea of &#8220;global disease&#8221;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Better coordination and continuity of care between primary and specialised care&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduces the perception of stroke as a chronic disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">In line with the Treatment Adherence Plan designed by Farmaindustria<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Easier dosage planning&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Better management of chronic patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Disadvantages</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risk of trivialising treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reluctance to changing treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Skipping a dose has worse consequences&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lack of flexibility in components and dosage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment may need to be supplemented&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not suitable for all patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">National trade association for Spanish-based pharmaceutical companies&#46;</p>"
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Implications of the use of cardiovascular polypills for cerebrovascular disease prevention&#46;</p>"
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      ]
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        "etiqueta" => "Table 2"
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        "mostrarFloat" => true
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">CVRF&#58; cardiovascular risk factors&#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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Recommended&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Not recommended&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atherothrombotic stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardioembolic stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lacunar stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with stroke but not presenting arterial hypertension or dyslipidaemia<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cryptogenic stroke associated with CVRF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intolerance to or contraindications for any of the polypill monocomponents&nbsp;\t\t\t\t\t\t\n
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                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Favourable and unfavourable clinical situations for use of cardiovascular polypills for cerebrovascular disease prevention&#46;</p>"
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspicion of poor treatment adherence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Polymedication&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Elderly patients&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple vascular diseases or history of atherothrombosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Young patients who are active workers or need to travel frequently&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patient preference for CV polypill&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Patients profiles with preferential indication for cardiovascular polypills for cerebrovascular disease prevention&#46;</p>"
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      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:53 [
            0 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Instituto Nacional de Estad&#237;stica 2012&#46; Available from&#58; <a target="_blank" href="http://www.ine.es/">http&#58;&#47;&#47;www&#46;ine&#46;es</a> &#91;accessed 14&#46;02&#46;17&#93;&#46;"
                ]
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            1 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Organizaci&#243;n Mundial de la Salud&#46; Enfermedades cardiovasculares&#46; Nota descriptiva&#46; Ene de 2015&#46; Available from&#58; <a target="_blank" href="http://www.who.int/mediacentre/factsheets/fs317/es/">http&#58;&#47;&#47;www&#46;who&#46;int&#47;mediacentre&#47;factsheets&#47;fs317&#47;es&#47;</a> &#91;accessed 4&#46;04&#46;17&#93;&#46;"
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0280"
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                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "J&#46; Lopez-Sendon"
                            1 => "J&#46;R&#46; Gonzalez-Juanatey"
                            2 => "F&#46; Pinto"
                            3 => "J&#46; Cuenca Castillo"
                            4 => "L&#46; Badimon"
                            5 => "R&#46; Dalmau"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Rev Esp Cardiol &#40;Engl Ed&#41;"
                        "fecha" => "2015"
                        "volumen" => "68"
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                    ]
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                ]
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            ]
            3 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An alarming threat to secondary prevention&#58; low compliance &#40;lifestyle&#41; and poor adherence &#40;drugs&#41; &#91;art&#237;culo en espa&#241;ol&#93;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "V&#46; Fuster"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Esp Cardiol &#40;Engl Ed&#41;"
                        "fecha" => "2012"
                        "volumen" => "65"
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                        "paginaFinal" => "16"
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                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A step ahead in secondary prevention of cardiovascular risk&#46; Consensus document on clinical use of the polypill"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "J&#46;R&#46; Gonzalez-Juanatey"
                            1 => "J&#46;M&#46; Mostaza"
                            2 => "J&#46;M&#46; Lobos"
                            3 => "B&#46; Abarca"
                            4 => "J&#46;L&#46; Llisterri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Esp Cardiol &#40;Engl Ed&#41;"
                        "fecha" => "2016"
                        "volumen" => "69"
                        "paginaInicial" => "547"
                        "paginaFinal" => "550"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment with atorvastatin to the National Cholesterol Educational Program goal versus &#8216;usual&#8217; care in secondary coronary heart disease prevention&#46; The GREek Atorvastatin and Coronary-heart-disease Evaluation &#40;GREACE&#41; study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46;G&#46; Athyros"
                            1 => "A&#46;A&#46; Papageorgiou"
                            2 => "B&#46;R&#46; Mercouris"
                            3 => "V&#46;V&#46; Athyrou"
                            4 => "A&#46;N&#46; Symeonidis"
                            5 => "E&#46;O&#46; Basayannis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1185/030079902125000787"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Med Res Opin"
                        "fecha" => "2002"
                        "volumen" => "18"
                        "paginaInicial" => "220"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12201623"
                            "web" => "Medline"
                          ]
                        ]
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                    ]
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            6 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Validation of primary and secondary outcomes and classification of mode of death among patients with clinical evidence of heart failure after a myocardial infarction&#58; a report from the Acute Infarction Ramipril Efficacy &#40;AIRE&#41; Study Investigators"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;G&#46; Cleland"
                            1 => "L&#46; Erhardt"
                            2 => "A&#46;S&#46; Hall"
                            3 => "C&#46; Winter"
                            4 => "S&#46;G&#46; Ball"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Cardiovasc Pharmacol"
                        "fecha" => "1993"
                        "volumen" => "22"
                        "numero" => "Suppl&#46; 9"
                        "paginaInicial" => "S22"
                        "paginaFinal" => "S27"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7514237"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "The Acute Infarction Ramipril Efficacy &#40;AIRE&#41; Study Investigators"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
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Article information

ISSN: 21735808
Original language: English

DOI:10.1016/j.nrleng.2017.10.008

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	8	2	10
2024 October	50	8	58
2024 September	28	7	35
2024 August	31	3	34
2024 July	18	3	21
2024 June	28	2	30
2024 May	15	7	22
2024 April	35	6	41
2024 March	58	6	64
2024 February	45	10	55
2024 January	26	5	31
2023 December	31	9	40
2023 November	28	4	32
2023 October	39	7	46
2023 September	21	6	27
2023 August	27	5	32
2023 July	27	7	34
2023 June	39	8	47
2023 May	77	13	90
2023 April	59	3	62
2023 March	43	1	44
2023 February	31	6	37
2023 January	22	4	26
2022 December	31	9	40
2022 November	44	10	54
2022 October	37	16	53
2022 September	25	13	38
2022 August	26	12	38
2022 July	15	9	24
2022 June	31	7	38
2022 May	34	9	43
2022 April	36	9	45
2022 March	57	15	72
2022 February	75	12	87
2022 January	88	20	108
2021 December	44	14	58
2021 November	37	14	51
2021 October	61	26	87
2021 September	49	20	69
2021 August	53	10	63
2021 July	25	12	37
2021 June	33	13	46
2021 May	38	13	51
2021 April	82	31	113
2021 March	41	13	54
2021 February	29	12	41
2021 January	32	10	42
2020 December	22	10	32
2020 November	20	4	24
2020 October	20	3	23
2020 September	19	15	34
2020 August	26	13	39
2020 July	17	14	31
2020 June	31	10	41
2020 May	27	13	40
2020 April	19	2	21
2020 March	27	9	36
2020 February	33	8	41
2020 January	24	14	38
2019 December	20	11	31
2019 November	16	6	22
2019 October	15	5	20
2019 September	11	2	13
2019 August	10	6	16

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