Clinical Research
Safety and efficacy of fimasartan in Mexican patients with grade 1–2 essential hypertension
Seguridad y eficacia de fimasartán en pacientes mexicanos con hipertensión esencial de grados 1–2
Ernesto G. Cardona-Muñoza,d, Agustín López-Alvaradob, Ignacio Conde-Carmonac,
, Gerardo Sánchez-Mejoradac, Sara Pascoe-Gonzálezd, Ramiro G. Banda-Elizondoe, Armando García-Castillof, Guillermo González-Gálvezg, Raúl G. Velasco-Sánchezh, Maricela Vidrio-Velázquezi, José L. Leiva-Ponsj, Efraín Villeda-Espinosak, Arturo Guerra-Lópezl, Ramón M. Esturau-Santalom
Corresponding author
Ignacio.conde@stendhalpharma.com
Corresponding author at: Av. Camino a Santa Teresa No. 1040, Mezanine 1, Colonia Jardines en la Montaña, Delegación Tlalpan, C.P.: 14210, Ciudad de México, Mexico.
Corresponding author at: Av. Camino a Santa Teresa No. 1040, Mezanine 1, Colonia Jardines en la Montaña, Delegación Tlalpan, C.P.: 14210, Ciudad de México, Mexico.
a Investigación Clínica Especializada, Sociedad Civil, Guadalajara, Jalisco, Mexico
b Núcleo Médico La Paz, Guadalajara, Jalisco, Mexico
c Específicos Stendhal, S.A. de C.V., Ciudad de México, Mexico
d Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico
e Centro de Estudios Clínicos y Especialidades Médicas, Monterrey, Nuevo León, Mexico
f Cardiolink Clinical Trials, Monterrey, Nuevo León, Mexico
g Instituto Jalisciense de Investigación en Diabetes y Obesidad S.C., Guadalajara, Jalisco, Mexico
h Hospital Dr. Ángel Leaño, Zapopan, Jalisco, Mexico
i Consultorio Médico Privado, Colonia Americana, Guadalajara, Jalisco, Mexico
j Hospital Central “Dr. Ignacio Morones Prieto”, San Luis Potosí, San Luis Potosí, Mexico
k Hospital de Jesús IAP, Ciudad de México, Mexico
l Centro Médico Excel, Tijuana, Baja California, Mexico
m Hospital Civil de Guadalajara “Fray Antonio Alcalde”, Guadalajara, Jalisco, Mexico
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Camino a Santa Teresa No. 1040, Mezanine 1, Colonia Jardines en la Montaña, Delegación Tlalpan, C.P.: 14210, Ciudad de México, Mexico." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Seguridad y eficacia de fimasartán en pacientes mexicanos con hipertensión esencial de grados 1–2" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1115 "Ancho" => 1610 "Tamanyo" => 102346 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Proportion of subjects achieving treatment target (DBP <90<span class="elsevierStyleHsp" style=""></span>mmHg and SBP <140<span class="elsevierStyleHsp" style=""></span>mmHg).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The Mexican Encuesta Nacional de Salud (ENSA, <span class="elsevierStyleItalic">National Health and Nutrition</span> Survey),<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">1</span></a> reported a prevalence of arterial hypertension in the adult population of 31.5%, with 47.3% of these hypertensive subjects being unaware of their condition.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">1</span></a> In spite of increasing levels of awareness, an alarming proportion (49.8%) of known hypertensive patients remains uncontrolled.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">1</span></a> To effectively address this public health problem, significant improvements on the diagnosis and management of this condition as well as safe and effective treatment options are needed.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Fimasartan (FMS) is a newly developed angiotensin II receptor antagonist resulting from a bioisosteric replacement of losartan's imidazole moiety with a pyrimidin-4(3H)-one part that confers this agent with the highest affinity to the AT1 receptor among drugs from this class (IC50<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.42<span class="elsevierStyleHsp" style=""></span>nM; Ki<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6.3E−11<span class="elsevierStyleHsp" style=""></span>M).<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">2</span></a> Results from clinical studies in the Eastern-Asian population have shown that Fimasartan is not inferior and may be superior to losartan and valsartan,<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">3,4</span></a> and that its antihypertensive effect is evident after two treatment weeks.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">5</span></a> FMS undergoes minimal hepatic metabolism, mainly by CYP3A4, which is well known for showing a marked genetic variability that may significantly influence drug disposition and therapeutic effect in different ethnic groups.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The safety and efficacy of FMS have only been systematically explored in Eastern-Asian subjects, therefore, the above described potential for differences in drug disposition and the possibility for this agent to show different efficacy and safety profiles in the Mexican population<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">8,9</span></a> require further assessment.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The purpose of this study was to evaluate the efficacy and safety of daily doses of 60<span class="elsevierStyleHsp" style=""></span>mg and 120<span class="elsevierStyleHsp" style=""></span>mg fimasartan, with or without 12.5<span class="elsevierStyleHsp" style=""></span>mg hydrochlorothiazide in Mexican subjects with essential hypertension grades 1–2.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Method and patients</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Inclusion criteria</span><p id="par0025" class="elsevierStylePara elsevierViewall">Subjects eligible to participate in the study were hypertension treatment naïve consenting adults, 18 years of age or older, with a baseline sitting diastolic blood pressure consistent with the diagnosis of grade 1 or 2 essential hypertension (diastolic blood pressure [DBP] ≥90 ≤109<span class="elsevierStyleHsp" style=""></span>mmHg). Not adequately controlled subjects already on monotherapy – provided that their treating physician considered them as suitable for a two-week washout period, were also eligible for the study.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Exclusion criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">Subjects with grade ≥3 hypertension (systolic blood pressure [SBP] ≥180<span class="elsevierStyleHsp" style=""></span>mmHg and/or DBP ≥110<span class="elsevierStyleHsp" style=""></span>mmHg); secondary hypertension; uncontrolled type II diabetes mellitus (HbA1c<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>9%); morbid obesity (BMI ≥40<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>); renal dysfunction (creatinine ≥1.5 times above the upper limit of the normal range), liver dysfunction (aspartate aminotransferase and/or alanine aminotransferase ≥1.5 times the upper limit of the normal range), gastrointestinal or hematological diseases or conditions with a potential to affect the absorption, distribution, metabolism and excretion of the study drugs; a history of myocardial infarction, severe coronary artery disease or clinically significant congestive heart failure within 6 months prior to the screening visit; auto-immune or connective tissue disease and clinically significant laboratory test abnormalities according to the investigator's judgment were not considered eligible to participate; additional exclusion criteria were the use of concomitant treatments which could affect blood pressure, known allergies or contraindication to the use of angiotensin II receptor antagonists, pregnant or breastfeeding women or in the case of women with childbearing potential, the rejection to use an effective contraceptive method (in accordance with the investigator's judgment), a history of alcohol or drug abuse, clinical trial participation within 6 months prior to screening and any other reason which in the investigator's opinion might contraindicate the participation of a subject in the study.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Method</span><p id="par0035" class="elsevierStylePara elsevierViewall">Eligible patients spontaneously attending to 13 participating sites in Mexico were enrolled to participate in the 24-week study treatment period. Starting on Day 0, and after a two week washout period in the case of subjects already receiving monotherapy, all patients received oral FMS 60<span class="elsevierStyleHsp" style=""></span>mg once a day (q.d.) during the first 8 weeks of the planned treatment period. Patients with a DBP <90<span class="elsevierStyleHsp" style=""></span>mmHg at treatment week 8 continued receiving the same dose for up to 24 weeks; those with week 8 DBP ≥<span class="elsevierStyleHsp" style=""></span>90<span class="elsevierStyleHsp" style=""></span>mmHg were then randomized to receive either FMS 120<span class="elsevierStyleHsp" style=""></span>mg q.d. or a fixed-dose combination tablet of fimasartan<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>hydrochlorothiazide (FMS/HCTZ) 60<span class="elsevierStyleHsp" style=""></span>mg/12.5<span class="elsevierStyleHsp" style=""></span>mg q.d. At week 12, patients randomized at week 8 maintaining a DBP<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>90<span class="elsevierStyleHsp" style=""></span>mmHg were escalated to open treatment with the fixed dose combination tablet of FMS 120<span class="elsevierStyleHsp" style=""></span>mg/HCTZ 12.5<span class="elsevierStyleHsp" style=""></span>mg q.d. for the remaining 12 weeks of the study (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). At all visits, subjects were instructed to take one tablet of their assigned medication in the morning, with or without food.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Included subjects underwent a medical evaluation including physical exam, vital signs, safety laboratory analyses, assessments of treatment adherence (by means of tablet counting) and assessments of occurrence of adverse events at baseline and at treatment weeks 4, 8, 12, 16, 20 and 24.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Randomization Method. At the end of treatment week 8, subjects not achieving the target (DBP <90<span class="elsevierStyleHsp" style=""></span>mmHg) were randomized by means of a computer-generated randomization list (simple randomization with a 1:1 allocation ratio), to receive either FMS 120<span class="elsevierStyleHsp" style=""></span>mg q.d. or FMS/HCTZ 60<span class="elsevierStyleHsp" style=""></span>mg/12.5<span class="elsevierStyleHsp" style=""></span>mg q.d. The randomization sequence was administered by an independent third party, so that sponsor's staff, investigators and enrolled subjects were blinded to the randomization list.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Blood pressure measurement was performed on the same arm at each clinic visit by either the principal investigator or designated medical personnel experienced and trained in the use of identical calibrated sphygmomanometers (Tycos 767, Welch Allyn) provided to each participating site with appropriate cuffs to accommodate the subject's arm circumference. Subjects had to refrain from performing exercise and/or consume tobacco or coffee for at least 30<span class="elsevierStyleHsp" style=""></span>min prior to blood pressure measurements. Following 5<span class="elsevierStyleHsp" style=""></span>min of rest in the sitting position, the average of two consecutive blood pressure measurements (2<span class="elsevierStyleHsp" style=""></span>min apart from each other) was obtained with the individual and average results recorded on the subject's charts.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Efficacy endpoints</span><p id="par0055" class="elsevierStylePara elsevierViewall">The primary study endpoint was the change from baseline DBP at treatment week 8 (FMS 60<span class="elsevierStyleHsp" style=""></span>mg q.d). Secondary efficacy endpoints included week 8 SBP change from baseline, treatment-week 12 blood pressure changes from treatment week 8 (subjects randomized to FMS 120<span class="elsevierStyleHsp" style=""></span>mg q.d. or FMS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HCTZ 60<span class="elsevierStyleHsp" style=""></span>mg/12.5<span class="elsevierStyleHsp" style=""></span>mg q.d.), treatment week 24 blood pressure changes from treatment week 12 (non-responding randomized subjects escalated to daily FMS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HCTZ 120/12.5<span class="elsevierStyleHsp" style=""></span>mg doses at treatment week 12), blood pressure changes from baseline in subjects receiving 60<span class="elsevierStyleHsp" style=""></span>mg FMS q.d. during the 24 week treatment period and between randomized groups differences on treatment week blood pressure changes from treatment week 8.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Safety endpoints</span><p id="par0060" class="elsevierStylePara elsevierViewall">Safety endpoints consisted on the incidence of adverse events, including clinically significant treatment emergent changes on vital signs, ECG parameters, and clinical laboratory measurements (complete blood counts, blood chemistry and urine examinations).</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">A sample size of 248 subjects was estimated as sufficient to detect a 1.4<span class="elsevierStyleHsp" style=""></span>mmHg difference in the change from baseline DBP between FMS and an assumed weighted mean change from baseline DBP of −8.375<span class="elsevierStyleHsp" style=""></span>mmHg for telmisartan as estimated from previously published results,<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">10–16</span></a> assuming a DBP standard deviation of 6<span class="elsevierStyleHsp" style=""></span>mmHg; with 95% power and a two-tailed 5% significance level, using the sampsi command on Stata-12 (one sample comparison of mean to hypothesized value)<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">17</span></a>; a final sample size of 270 subjects was determined to account for an estimated 8% drop-out rate assumed based on the dropout rate observed in similar studies.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">10,11,16</span></a> Blood pressure changes from baseline and response rates were analyzed on an intention to treat (ITT) population consisting on all subjects taking at least one dose of study medication and one post-baseline blood pressure measurement using the multivariate normal procedure on NCSS10 (NCSS Statistical Software)<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">18</span></a> to impute missing data. Safety analysis was performed on all subjects who received at least one dose of the study medications. To explore the robustness of the primary efficacy analysis, efficacy assessments were also conducted on a per-protocol population consisting on all subjects who completed the planned treatment period with no major protocol deviations (protocol deviations: DBP <90<span class="elsevierStyleHsp" style=""></span>mmHg at screening: 8 cases, included subjects with grade 3 [SBP >180<span class="elsevierStyleHsp" style=""></span>mmHg]: 3 cases, subjects assigned to an erroneous treatment at week 8: 6 cases, 1 subject erroneously assigned to treatment with FMS 60<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HCTZ 12.5<span class="elsevierStyleHsp" style=""></span>mg at week 4, 1 subject erroneously assigned to FMS 120<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HCTZ 12.5<span class="elsevierStyleHsp" style=""></span>mg at week 16 and 28 additionally withdrawn subjects). Within-group changes from baseline/reference point in time (i.e., week 8 for randomized subjects and week 12 for subjects escalated to the fixed dose combination of FMS 120<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HCTZ 12.5<span class="elsevierStyleHsp" style=""></span>mg q.d.) were analyzed using paired <span class="elsevierStyleItalic">t</span> tests, whereas differences between randomized treatment groups were analyzed using Student's <span class="elsevierStyleItalic">t</span> tests in the case of independent means and relative risks in the case of proportions of subjects achieving therapeutic target in both groups. Blood pressure changes from baseline observed in the subset of patients treated with 60<span class="elsevierStyleHsp" style=""></span>mg FMS once daily over the 24 week treatment period were analyzed by means of repeated measures analysis of variance. We used two tailed tests performed at a 5% significance level.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Ethical considerations. This study was conducted in compliance with the principles established in the Declaration of Helsinki. The protocol was approved by the Commission for Sanitary Approval (CAS) of the Mexican <span class="elsevierStyleItalic">Comisión Federal Para la Protección Contra Riesgos Sanitarios</span> (COFEPRIS). Consent was granted by signing a written patient information and informed consent form, previously reviewed and approved by both relevant local ethics committees and the CAS.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">This study was conducted from April 2013 to August 2014.</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Study population</span><p id="par0080" class="elsevierStylePara elsevierViewall">Two hundred and seventy two (104 [38.2%] treatment naïve and 168 [61.8%] treatment experienced patients completing the planned washout period), eligible Mexican subjects, started the initial 8 weeks of planned treatment with FMS 60<span class="elsevierStyleHsp" style=""></span>mg q.d. with 33 subjects being withdrawn before completing the planned 24 week treatment period of the study (lost to follow-up: 17 [6.25%], consent withdrawal: 5 [1.84%], non-serious adverse event: 4 [1.47%], treatment non-compliance: 3 [1.10%], investigator's decision: 1 [0.37%], conflict of interest: 1 [0.37%], serious adverse event: 1 [0.37%] and DBP <90<span class="elsevierStyleHsp" style=""></span>mmHg: 1 [0.37]); therefore 239 (87.9%) enrolled subjects completed the trial according to the study protocol (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Only five subjects where withdrawn because of the occurrence of non-serious and serious adverse events.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">The study population comprised a broad range of patients with essential hypertension, including a significant proportion of subjects with co-morbidities such as obesity (with mean waist–hip ratios of 0.90<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.07 and 0.97<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.05 for female and male subjects, respectively), diabetes, dyslipidemia and coronary heart disease (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Estimated global assigned treatment adherence rate was 98.6%.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Efficacy</span><p id="par0090" class="elsevierStylePara elsevierViewall">By treatment week 8, FMS 60<span class="elsevierStyleHsp" style=""></span>mg q.d. reduced both DBP and SBP by 11.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.9<span class="elsevierStyleHsp" style=""></span>mmHg (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.00001) and 16.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.1<span class="elsevierStyleHsp" style=""></span>mmHg (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.00001), respectively; with 75.4% (205/272) of the subjects achieving their treatment target (defined as a SiDBP <90<span class="elsevierStyleHsp" style=""></span>mmHg). By treatment week 12, 29 and 28 patients randomized to FMS 120<span class="elsevierStyleHsp" style=""></span>mg q.d. or to the fixed dose combination of FMS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HCTZ 60/12.5<span class="elsevierStyleHsp" style=""></span>mg q.d. showed significant blood pressure decreases from their week 8 values, with 58.6% (17/29) and 78.6% (22/28) subjects achieving treatment target. At week 12, twelve non-responding randomized subjects (8 from the FMS 120<span class="elsevierStyleHsp" style=""></span>mg q.d. and 4 from the FMS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HCTZ 60/12.5<span class="elsevierStyleHsp" style=""></span>mg q.d. groups), received FMS 120<span class="elsevierStyleHsp" style=""></span>mg/HCTZ 12.5<span class="elsevierStyleHsp" style=""></span>mg q.d. until the end of the planned treatment period and showed significant DBP and SBP reductions from their week 12 values, with 75% of them achieving treatment target by week 24 (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Analysis of the time course of the blood pressure lowering effect in the subgroup of subjects assigned to treatment with 60<span class="elsevierStyleHsp" style=""></span>mg fimasartan once daily throughout the study showed sustained systolic and diastolic pressure decreases which were statistically significant at all post-baseline assessments (i.e., <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001 for all pairwise comparisons between weeks 4, 8, 12, 16, 20 and 24 blood pressure decreases and baseline), with a trend to further blood pressure decreases throughout the study (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Of note, the treatment-to-target escalation strategy explored in this study resulted in a high proportion of participating subjects achieving both a DBP <90<span class="elsevierStyleHsp" style=""></span>mmHg and a SBP <140<span class="elsevierStyleHsp" style=""></span>mmHg (87.1%) by the end of the planned 24-week treatment period (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Baseline comparison of subjects randomized at week 8 showed modest, non-significant differences between resulting groups with subjects assigned to FMS/HCTZ 60/12.5<span class="elsevierStyleHsp" style=""></span>mg being younger (53.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.1<span class="elsevierStyleHsp" style=""></span>mmHg vs. 57.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.2<span class="elsevierStyleHsp" style=""></span>mmHg, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.073) and with a slightly lower baseline SBP (155.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.5<span class="elsevierStyleHsp" style=""></span>mmHg vs. 158.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.8<span class="elsevierStyleHsp" style=""></span>mmHg, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.34) in comparison with subjects randomized to FMS 120<span class="elsevierStyleHsp" style=""></span>mg q.d. (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Between-treatment group comparisons showed that patients randomized to FMS/HCTZ 60/12.5<span class="elsevierStyleHsp" style=""></span>mg q.d. had greater reductions on both SBP and DBP which were not statistically significant (mean difference<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD [95% confidence interval] of 2.51<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.77 [−1.62, 6.63] and −4.49<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.86 [−2.33, 11.32] for the DBP and SBP, respectively. In comparison with subjects assigned to FMS 120<span class="elsevierStyleHsp" style=""></span>mg q.d., the proportion of subjects assigned to FMS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HCTZ 60/12.5<span class="elsevierStyleHsp" style=""></span>mg q.d. who achieved treatment target was higher (12/29, 58.6% vs. 22/28, 78.6%); this difference was, however, not statistically significant (RR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.34 [95% confidence interval: 0.94, 2.01], <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.11).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The exploratory analysis of changes from reference blood pressure values and response rates performed in the per protocol population (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>225) was consistent with results obtained with the ITT population in terms of the magnitude of effect and statistical significance, thus supporting the robustness of the primary efficacy analyses (Supplementary Data).</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Safety</span><p id="par0110" class="elsevierStylePara elsevierViewall">During the whole study period, 64 of 272 subjects (23.5%) experienced 132 adverse events (AEs); most of which were mild to moderate in intensity (125/132 events, 94.7%) (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). Adverse events considered as causally related with the study drugs by the participating investigators were identified in 25/272 (9.19%) subjects. The most frequent related AEs were headache (3.7%), dry mouth (1.1%), non-clinically significant, transient liver enzymes increase (1.1%) and dizziness (0.7%). Two non-serious events (0.7%) of hypotension attributed to FMS were reported, one event was solved with treatment discontinuation and the other resolved spontaneously. Three serious adverse events (one event of narrow angle glaucoma exacerbation and two events of traumatic bone fracture) were observed, all of which resolved with no sequels. None of the serious adverse events were considered by the investigators as related to the study drug. These observations are in accordance with previously reported results.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">3,4</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">Non-clinically relevant changes of serum creatinine and potassium (K+) were observed. Serum creatinine change from baseline at week 24 was 0.02<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.1<span class="elsevierStyleHsp" style=""></span>mg/dL (from a baseline value of 0.83<span class="elsevierStyleHsp" style=""></span>mg/dL) while serum K+ change from baseline at week 24 was 0.06<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.40 mEq/L (from a baseline value of 4.11<span class="elsevierStyleHsp" style=""></span>mEq/L). No adverse events related with clinically significant changes of serum Cr and/or K+ values were observed.</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">A series of observational studies and clinical trials indicate that commonly used antihypertensive agents may produce variable blood pressure lowering responses and potentially differing long-term outcomes in different ethnic populations when used as monotherapy.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">8,19–21</span></a> Still, specific information on the safety and efficacy of available anti-hypertensive medications – both in terms of blood pressure lowering effects and clinically relevant outcomes, in diverse ethnic groups is lacking.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">22</span></a> Data on the efficacy and safety of antihypertensive agents, specially ARBs, among Mexicans remains limited due to the under-representation of this population in clinical trials; with most of the data primarily restricted to retrospective subgroup analyses.<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">23,24</span></a> The results of our study represent a contribution toward filling this gap.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In this Mexican experience with grade 1–2 essential hypertension subjects, FMS monotherapy at a dose of 60<span class="elsevierStyleHsp" style=""></span>mg q.d. resulted in sustained, clinically and statistically significant blood pressure reductions from baseline with 75.4% of subjects achieving the DBP treatment target (DBP <90<span class="elsevierStyleHsp" style=""></span>mmHg). Interestingly, rather than showing an additive blood pressure lowering effect of subsequent treatment escalation, our treat to goal escalation strategy allowed the identification of subsets of non-responders at weeks 8 and 12 with blood pressure levels very similar to their baseline values and who eventually showed clinically relevant blood pressure value decreases with subsequent treatment escalation, resulting in a high proportion of subjects (87.1%) achieving both a DBP <90<span class="elsevierStyleHsp" style=""></span>mmHg and a SBP <140<span class="elsevierStyleHsp" style=""></span>mmHg. We think that this response pattern merits further analysis to determine whether other factors such as renin-angiotensin system-related polymorphisms may influence treatment response in this population.</p><p id="par0130" class="elsevierStylePara elsevierViewall">In conducting this experience, we sought to obtain a reliable estimate of FMSs blood pressure lowering effect in a sample of Mexican subjects by systematically studying a patient cohort based on the same general selection criteria used during the phase III assessment of the efficacy and safety of the drug in the Korean population.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">3,4,25</span></a> The resulting estimates for both DBP and SBP 8 week change from baseline with FMS 60<span class="elsevierStyleHsp" style=""></span>mg q.d. in our experience were consistent with those published by Lee et al.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">3</span></a> (−11.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.9 vs −11.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.6 and −16.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.1 vs −17.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.5, respectively) and similar to those reported by Lee H. and Kim K.S. et al.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">4</span></a> (−11.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.9 vs. −14.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.2 and −16.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.1 vs 18.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.0, respectively), thus supporting the notion of a similar efficacy of FMS in both the Korean and Mexican population.</p><p id="par0135" class="elsevierStylePara elsevierViewall">The above results are consistent with our initial assumption of minimal to no effect of intrinsic ethnic factors on the tolerability and efficacy of FMS based on its linear pharmacokinetics, flat efficacy/concentration curve, wide therapeutic dose range (which suggest a low potential for differences in tolerability among differing ethnic groups), its minimal hepatic metabolism and low potential for drug-drug interactions as described on the ICH guidance document E5R1 regarding the acceptance of foreign data,<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">26</span></a> and supports the usefulness of this document as a guidance for the regulatory acceptance of foreign clinical data.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Observed differences in terms of the blood pressure lowering effect between subjects randomized to 120<span class="elsevierStyleHsp" style=""></span>mg FMS q.d. or to 60/12.5<span class="elsevierStyleHsp" style=""></span>mg FMS/HCTZ q.d., are consistent with existing evidence of a superior effect of combined treatment over monotherapy up-titration,<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">27</span></a> but lacked the power needed to reach statistical significance; considered in the context of existing evidence, this result suggests that, in the absence of contraindications to the use of HCTZ, the FMS/HCTZ combination should be the preferred treatment escalation strategy for patients not responding to FMS monotherapy.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The safety and tolerability findings among this cohort of Mexican subjects exposed to FMS alone or in combination with HCTZ were similar to those observed during the initial clinical development of the compound in Korea.</p><p id="par0150" class="elsevierStylePara elsevierViewall">Limitations of this study include its open and non-controlled nature and the fact that sample size estimation was not conducted to provide sufficient power for randomized treatment-group comparisons; the fact that the study was prospectively conducted in a cohort of subjects with a pattern of co-morbidities typically observed among Mexican essential hypertension patients, with a clearly defined “zero time” to determine eligibility and baseline characteristics, and selection criteria and statistical methods (e.g., ITT analysis) similar to those used in controlled clinical trials previously conducted with fimasartan allowed us to obtain estimates of the safety and efficacy of the drug consistent with those observed in Korean subjects.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conclusion</span><p id="par0155" class="elsevierStylePara elsevierViewall">Fimasartan 60 or 120<span class="elsevierStyleHsp" style=""></span>mg, alone or in combination with 12.5<span class="elsevierStyleHsp" style=""></span>mg HCTZ once a day is safe and effective in Mexican patients with grade 1–2 essential hypertension.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Ethical disclosures</span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Protection of human and animal subjects</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association (Declaration of Helsinki).</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Confidentiality of data</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Right to privacy and informed consent</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Funding</span><p id="par0175" class="elsevierStylePara elsevierViewall">Thus study was funded by Específicos Stendhal S.A. de C.V. with additional financial support from the Mexican Consejo Nacional de Ciencia y Tecnología (Project number: PEI-467/2013-199007).</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Author contributions</span><p id="par0180" class="elsevierStylePara elsevierViewall">Ernesto Germán Cardona-Muñoz M.D., Maricela Vidrio-Velázquez M.D., Arturo Guerra-López M.D., Efrain Villeda-Espinosa M.D., Armando García-Castillo M.D., Guillermo González-Gálvez M.D., Sara Pascoe-González M.D., Jose Luis Leiva-Pons M.D., Ramiro Banda-Elizondo M.D., Agustin López-Alvarado M.D., Raul Gerardo Velasco-Sanchez M.D. and Ramón M. Esturau-Santalo M.D. received study drug, blood pressure measurement devices and financial support from Específicos Stendhal S.A. de C.V. for their participation in the study.</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conflicts of interest</span><p id="par0185" class="elsevierStylePara elsevierViewall">Ignacio Conde-Carmona M.D. and Gerardo Sánchez-Mejorada M.D. are employees of Específicos Stendhal S.A. de C.V.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres933294" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec907638" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres933293" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec907639" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Method and patients" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Inclusion criteria" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Exclusion criteria" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Method" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Efficacy endpoints" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Safety endpoints" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Efficacy" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Safety" ] ] ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0070" "titulo" => "Conclusion" ] 9 => array:3 [ "identificador" => "sec0075" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0080" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0085" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0090" "titulo" => "Right to privacy and informed consent" ] ] ] 10 => array:2 [ "identificador" => "sec0095" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0100" "titulo" => "Author contributions" ] 12 => array:2 [ "identificador" => "sec0105" "titulo" => "Conflicts of interest" ] 13 => array:2 [ "identificador" => "xack315050" "titulo" => "Acknowledgements" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-11-03" "fechaAceptado" => "2017-01-09" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec907638" "palabras" => array:5 [ 0 => "Hypertension" 1 => "Drug therapy" 2 => "Angiotensin II Type 1 receptor blockers" 3 => "Fimasartan" 4 => "Mexico" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec907639" "palabras" => array:5 [ 0 => "Hipertensión" 1 => "Tratamiento farmacológico" 2 => "Bloqueadores de receptor de angiotensina II de tipo 1" 3 => "Fimasartán" 4 => "México" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate efficacy and safety of 60<span class="elsevierStyleHsp" style=""></span>mg and 120<span class="elsevierStyleHsp" style=""></span>mg Fimasartan (FMS) alone or combined with 12.5<span class="elsevierStyleHsp" style=""></span>mg hydrochlorothiazide (HCTZ) in a Mexican population.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A six month, treat-to-target, open study was conducted on subjects with grade 1-2 hypertension. The subjects were initially treated with 60<span class="elsevierStyleHsp" style=""></span>mg FMS once daily. In week 8, those with Diastolic Blood Pressure (DBP) <90<span class="elsevierStyleHsp" style=""></span>mmHg continued on the same FMS dose during the rest of the study, while those with DBP ≥90<span class="elsevierStyleHsp" style=""></span>mmHg were randomised to either 120<span class="elsevierStyleHsp" style=""></span>mg FMS or 60<span class="elsevierStyleHsp" style=""></span>mg FMS + 12.5<span class="elsevierStyleHsp" style=""></span>mg HCTZ once daily. In week 12, randomised subjects with DBP ≥90<span class="elsevierStyleHsp" style=""></span>mmHg received 120<span class="elsevierStyleHsp" style=""></span>mg FMS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>12.5<span class="elsevierStyleHsp" style=""></span>mg HCTZ, while those achieving target continued with their assigned treatment until the end of the study.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">FMS 60<span class="elsevierStyleHsp" style=""></span>mg (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>272) decreased both DBP and Systolic Blood Pressure (SBP) by 11.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.9 (<span class="elsevierStyleItalic">p</span><.0001) and 16.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.1 (<span class="elsevierStyleItalic">p</span><.0001)<span class="elsevierStyleHsp" style=""></span>mmHg, respectively, with 75.4% of subjects reaching the treatment target. Subjects assigned to FMS 120<span class="elsevierStyleHsp" style=""></span>mg, FMS 60<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HCTZ 12.5<span class="elsevierStyleHsp" style=""></span>mg, or FMS 120<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HCTZ 12.5<span class="elsevierStyleHsp" style=""></span>mg once daily, showed significant reductions in DBP and SBP with their assigned treatment. At the end of the study, 237/272 subjects (87.1%) achieved a DBP<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>90<span class="elsevierStyleHsp" style=""></span>mmHg and an SBP<140<span class="elsevierStyleHsp" style=""></span>mmHg. The most frequently reported adverse reactions included headache (3.7%), dry mouth (1.1%), transient liver enzyme increase (1.1%), and dizziness (0.7%).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Fimasartan is safe and effective in Mexican subjects with grade 1-2 essential hypertension.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar la eficacia y la seguridad de 60 y 120<span class="elsevierStyleHsp" style=""></span>mg de fimasartán (FMS) solo o combinado con 12.5<span class="elsevierStyleHsp" style=""></span>mg de hidroclorotiazida (HCTZ) en población mexicana.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio abierto, de 24 semanas, con tratamiento escalado hasta el objetivo terapéutico en sujetos hipertensos grados 1–2. Tratamiento inicial: FMS 60<span class="elsevierStyleHsp" style=""></span>mg una vez al día; en la semana 8, los sujetos con presión arterial diastólica (PAD) <90<span class="elsevierStyleHsp" style=""></span>mmHg mantuvieron su tratamiento inicial durante el estudio, mientras que los sujetos con PAD ≥90<span class="elsevierStyleHsp" style=""></span>mmHg fueron aleatorizados a 120<span class="elsevierStyleHsp" style=""></span>mg de FMS o a 60<span class="elsevierStyleHsp" style=""></span>mg de FMS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>12.5<span class="elsevierStyleHsp" style=""></span>mg de HCTZ. En la semana 12, los sujetos aleatorizados con PAD ≥90<span class="elsevierStyleHsp" style=""></span>mmHg recibieron 120<span class="elsevierStyleHsp" style=""></span>mg de FMS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>12.5<span class="elsevierStyleHsp" style=""></span>mg de HCTZ; quienes alcanzaron el objetivo terapéutico mantuvieron su tratamiento asignado hasta finalizar el estudio.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">FMS 60<span class="elsevierStyleHsp" style=""></span>mg (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>272) disminuyó la PAD y la presión arterial sistólica (PAS) en 11.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.9 (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001) y 16.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.1 (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001)<span class="elsevierStyleHsp" style=""></span>mmHg, respectivamente, con logro del objetivo de tratamiento en el 75.4% de los sujetos. Los sujetos asignados a 120<span class="elsevierStyleHsp" style=""></span>mg de FMS, a 60<span class="elsevierStyleHsp" style=""></span>mg de FMS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>12.5<span class="elsevierStyleHsp" style=""></span>mg de HCTZ 12.5 y a 120<span class="elsevierStyleHsp" style=""></span>mg de FMS<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>12.5<span class="elsevierStyleHsp" style=""></span>mg de HCTZ mostraron reducciones significativas de PAD y PAS; al final del estudio, 237/272 sujetos (87.1%) lograron PAD <90 y PAS <140<span class="elsevierStyleHsp" style=""></span>mmHg. Las reacciones adversas más frecuentemente reportadas fueron: cefalea (3.7%), boca seca (1.1%), incremento de enzimas hepáticas (1.1%) y mareo (0.7%).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">FMS es seguro y eficaz en sujetos mexicanos con hipertensión esencial de grados 1–2.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">FIRME-1 (FImasaRtan inMExico-1).</p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Clinical Trial Registration: URL; <span class="elsevierStyleInterRef" id="intr0005" href="http://clinicaltrials.gov/">http://clinicaltrials.gov</span>. Unique identifier: <span class="elsevierStyleInterRef" id="intr0010" href="ctgov:NCT02466490">NCT02466490</span>.</p>" ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1747 "Ancho" => 2996 "Tamanyo" => 260059 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Study design.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2055 "Ancho" => 2639 "Tamanyo" => 374791 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Subject disposition.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1447 "Ancho" => 2178 "Tamanyo" => 167465 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Blood pressure lowering effect over time. (ITT population, fimasartan 60<span class="elsevierStyleHsp" style=""></span>mg once daily).</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1115 "Ancho" => 1610 "Tamanyo" => 102346 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Proportion of subjects achieving treatment target (DBP <90<span class="elsevierStyleHsp" style=""></span>mmHg and SBP <140<span class="elsevierStyleHsp" style=""></span>mmHg).</p>" ] ] 4 => 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:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Variable</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender female, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">154 (56.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Type 2 diabetes mellitus, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">105 (38.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dyslipidemia, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">104 (38.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peripheral venous insufficiency, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (3.67) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ischemic heart disease, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (2.94) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Previous myocardial infarction, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (2.94) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peripheral vascular disease, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (2.57) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Previous stroke, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (2.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart rate (bpm), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DBP (mmHg), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">94.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SBP (mmHg), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">150.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI (kg/m<span class="elsevierStyleSup">2</span>), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Overweight (25–29.9<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>), <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">99 (36) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obesity (≥30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>), <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">147 (54) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1577252.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Total study population baseline clinical characteristics.</p>" ] ] 5 => 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:2 [ "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">SD, standard deviation.</p>" "tablatextoimagen" => array:4 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment Week 8<br>Fimasartan 60<span class="elsevierStyleHsp" style=""></span>mg once a day (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>272)</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Basal DBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Week 8 DBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Change from Baseline (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI<span class="elsevierStyleInf">95</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">94.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">82.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−11.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−10.2, −12.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Basal SBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Week 8 SBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Change from baseline (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI<span class="elsevierStyleInf">95</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">150.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">134.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>16.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−16.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−14.3, −17.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1577253.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment Week 12<br>Fimasartan 120<span class="elsevierStyleHsp" style=""></span>mg once a day (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>29)</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Week 8 DBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Week 12 DBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Change from Week 8 (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI<span class="elsevierStyleInf">95</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">96.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">87.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−8.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−5.2, −11.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Week 8 SBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Week 12 SBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Change from Week 8 (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI<span class="elsevierStyleInf">95</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">155.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">143.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−12.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−7.5, −17.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1577248.png" ] ] 2 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment Week 12<br>Fimasartan/Hydrochlorothiazide 60/12.5<span class="elsevierStyleHsp" style=""></span>mg once a day (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>28)</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Week 8 DBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Week 12 DBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Change from Week 8 (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI<span class="elsevierStyleInf">95</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">95.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">84.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−10.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−7.9, −13.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Week 8 SBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Week 12 SBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Change from Week 8 (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI<span class="elsevierStyleInf">95</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">156.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">139.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>16.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−16.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−11.6, −21.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1577247.png" ] ] 3 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment Week 24<br>Fimasartan/Hydrochlorothiazide 120/12.5<span class="elsevierStyleHsp" style=""></span>mg once a day (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>12)</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Week 12 DBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Week 24 DBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Change from Week 12 (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI<span class="elsevierStyleInf">95</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">95.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">84.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−10.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−5.9, −15.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0006 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Week 12 SBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Week 24 SBP (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Change from Week 12 (mmHg)<br>Mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI<span class="elsevierStyleInf">95</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">153.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">139.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−14.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−7.4, −21.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1577251.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Blood pressure (BP) changes from reference values.</p>" ] ] 6 => 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:2 [ "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">SD, standard deviation.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment randomly assigned at Week 8</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Fimasartan 120</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg q</span>.<span class="elsevierStyleItalic">d</span>.<br><span class="elsevierStyleItalic">(n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">29)</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Fimasartan/HCTZ 60/12</span>.<span class="elsevierStyleItalic">5</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg q</span>.<span class="elsevierStyleItalic">d</span>.<br><span class="elsevierStyleItalic">(n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">28)</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p value</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.073 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Body mass index (kg/m<span class="elsevierStyleSup">2</span>), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.89 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender female, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (48.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 (55.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.79 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart rate (bpm), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.42 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline diastolic blood pressure (mmHg), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.41 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline systolic blood pressure (mmHg), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">158.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">155.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.34 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diastolic blood pressure, Week 8 (mmHg), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systolic blood pressure, Week 8 (mmHg), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">155.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">156.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.86 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1577250.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Subjects randomized at Week 8: baseline clinical characteristics (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>57).</p>" ] ] 7 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Fimasartan 60<span class="elsevierStyleHsp" style=""></span>mg once a day \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Fimasartan 120<span class="elsevierStyleHsp" style=""></span>mg once a day \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FMS/HCTZ 60/12.5<span class="elsevierStyleHsp" style=""></span>mg once a day \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FMS/HCTZ 120<span class="elsevierStyleHsp" style=""></span>g/12.5<span class="elsevierStyleHsp" style=""></span>mg once a day \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total subjects reporting an adverse event \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57 (20.95%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (1.10%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (2.20%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (0.73%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 (23.52%)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Number of AEs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">108 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">132 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mild \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AEs resulting in subject withdrawal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Number of subjects with SAEs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (1.10%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1577249.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">4 subjects reported the occurrence of adverse events (AEs) during the initial treatment period with fimasartan 60<span class="elsevierStyleHsp" style=""></span>mg once a day and during their subsequent treatment with either fimasartan 120<span class="elsevierStyleHsp" style=""></span>mg once daily, or with fimasartan/HCTZ at doses of 120<span class="elsevierStyleHsp" style=""></span>mg/12.5<span class="elsevierStyleHsp" style=""></span>mg once daily.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Treatment emergent adverse events.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:27 [ 0 => array:3 [ "identificador" => "bib0140" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hipertensión arterial: prevalencia, diagnóstico oportuno y tendencias en adultos Mexicanos" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "N. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 12 | 3 | 15 |
| 2024 October | 112 | 6 | 118 |
| 2024 September | 105 | 6 | 111 |
| 2024 August | 105 | 0 | 105 |
| 2024 July | 145 | 5 | 150 |
| 2024 June | 127 | 8 | 135 |
| 2024 May | 103 | 5 | 108 |
| 2024 April | 91 | 8 | 99 |
| 2024 March | 185 | 22 | 207 |
| 2024 February | 171 | 17 | 188 |
| 2024 January | 181 | 13 | 194 |
| 2023 December | 294 | 34 | 328 |
| 2023 November | 269 | 13 | 282 |
| 2023 October | 232 | 11 | 243 |
| 2023 September | 334 | 6 | 340 |
| 2023 August | 326 | 17 | 343 |
| 2023 July | 397 | 16 | 413 |
| 2023 June | 264 | 24 | 288 |
| 2023 May | 324 | 19 | 343 |
| 2023 April | 204 | 12 | 216 |
| 2023 March | 327 | 17 | 344 |
| 2023 February | 144 | 10 | 154 |
| 2023 January | 108 | 6 | 114 |
| 2022 December | 115 | 16 | 131 |
| 2022 November | 130 | 43 | 173 |
| 2022 October | 104 | 29 | 133 |
| 2022 September | 177 | 41 | 218 |
| 2022 August | 197 | 38 | 235 |
| 2022 July | 142 | 35 | 177 |
| 2022 June | 128 | 81 | 209 |
| 2022 May | 146 | 44 | 190 |
| 2022 April | 151 | 51 | 202 |
| 2022 March | 229 | 40 | 269 |
| 2022 February | 228 | 10 | 238 |
| 2022 January | 220 | 30 | 250 |
| 2021 December | 164 | 33 | 197 |
| 2021 November | 136 | 21 | 157 |
| 2021 October | 137 | 30 | 167 |
| 2021 September | 94 | 26 | 120 |
| 2021 August | 119 | 15 | 134 |
| 2021 July | 94 | 31 | 125 |
| 2021 June | 75 | 19 | 94 |
| 2021 May | 71 | 11 | 82 |
| 2021 April | 210 | 101 | 311 |
| 2021 March | 274 | 38 | 312 |
| 2021 February | 113 | 23 | 136 |
| 2021 January | 109 | 30 | 139 |
| 2020 December | 95 | 29 | 124 |
| 2020 November | 105 | 15 | 120 |
| 2020 October | 63 | 4 | 67 |
| 2020 September | 74 | 14 | 88 |
| 2020 August | 111 | 17 | 128 |
| 2020 July | 94 | 21 | 115 |
| 2020 June | 58 | 17 | 75 |
| 2020 May | 88 | 7 | 95 |
| 2020 April | 78 | 14 | 92 |
| 2020 March | 106 | 11 | 117 |
| 2020 February | 99 | 13 | 112 |
| 2020 January | 91 | 13 | 104 |
| 2019 December | 73 | 8 | 81 |
| 2019 November | 61 | 7 | 68 |
| 2019 October | 71 | 17 | 88 |
| 2019 September | 78 | 11 | 89 |
| 2019 August | 40 | 11 | 51 |
| 2019 July | 53 | 14 | 67 |
| 2019 June | 104 | 12 | 116 |
| 2019 May | 221 | 57 | 278 |
| 2019 April | 106 | 42 | 148 |
| 2019 March | 25 | 9 | 34 |
| 2019 February | 24 | 8 | 32 |
| 2019 January | 28 | 12 | 40 |
| 2018 December | 12 | 8 | 20 |
| 2018 November | 25 | 4 | 29 |
| 2018 October | 66 | 20 | 86 |
| 2018 September | 47 | 9 | 56 |
| 2018 August | 21 | 11 | 32 |
| 2018 July | 30 | 9 | 39 |
| 2018 June | 15 | 11 | 26 |
| 2018 May | 25 | 16 | 41 |
| 2018 April | 21 | 9 | 30 |
| 2018 March | 28 | 7 | 35 |
| 2018 February | 25 | 14 | 39 |
| 2018 January | 37 | 9 | 46 |
| 2017 December | 44 | 17 | 61 |
| 2017 November | 35 | 17 | 52 |
| 2017 October | 17 | 15 | 32 |
| 2017 September | 6 | 10 | 16 |
| 2017 August | 10 | 21 | 31 |
| 2017 July | 8 | 2 | 10 |
| 2017 June | 9 | 10 | 19 |
| 2017 May | 16 | 21 | 37 |
| 2017 April | 13 | 12 | 25 |
| 2017 March | 16 | 42 | 58 |
| 2017 February | 0 | 27 | 27 |
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