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hypertension&#44; smoking&#44; diabetes&#44; obesity&#44; psychosocial stress&#41; with the absence of three protective factors &#40;exercise&#44; daily diet rich in fruit and vegetables&#44; moderate alcohol intake&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">2</span></a> According to the prevalence of these risk factors and the magnitude of the estimated risk&#44; dyslipidemia showed the highest population attributable risk &#40;49&#46;2&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Similarly&#44; the risk factors for stroke were studied in the INTERSTROKE case-control study&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">3</span></a> Major risk factors identified were hypertension&#44; dyslipidemia&#44; smoking&#44; central obesity&#44; diabetes&#44; alcohol intake&#44; cardiac disease&#44; stress&#44; diet&#44; and physical inactivity&#46; Hypertension had the highest population attributable risk for stroke &#40;47&#46;8&#37;&#41;&#44; followed by dyslipidemia&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Overall&#44; hypertension and dyslipidemia&#44; both modifiable vascular risk factors&#44; are the major contributors to the annual incidence of myocardial infarction and ischemic stroke&#46; Furthermore&#44; it is acknowledged that these are mediated by arterial disease and thrombosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">2&#44;3</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Hypertension&#44; dyslipidemia and atherothrombosis in Portugal</span><p id="par0025" class="elsevierStylePara elsevierViewall">It is widely known that hypertension and dyslipidemia are two prevalent risk factors in the Portuguese population&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The first landmark study regarding arterial hypertension prevalence&#44; knowledge&#44; treatment and control was the PAP study&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">4</span></a> Among 5023 adult individuals&#44; a representative sample of the Portuguese population in 2003&#44; the prevalence of hypertension was 42&#46;1&#37;&#46; Of these&#44; 46&#46;1&#37; had a previous diagnosis of hypertension&#44; 39&#46;0&#37; were treated with anti-hypertensive drugs and only 11&#46;2&#37; had controlled hypertension&#46; More recently&#44; the Portuguese HYpertension and SAlt &#40;PHYSA&#41; study revealed a similar prevalence of hypertension &#40;43&#46;1&#37;&#41;&#44; but a higher proportion of knowledge &#40;62&#46;8&#37;&#41;&#44; treatment &#40;69&#46;9&#37;&#41; and control &#40;32&#46;1&#37;&#41;&#44; albeit still far from desirable goals&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">6</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the major Portuguese hypertension studies&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Regarding dyslipidemia&#44; several cross-sectional epidemiological studies have been performed in the last two decades&#44; however prevalence is more heterogeneous due to the use of different criteria&#44; time points and cholesterol thresholds&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In the BECEL study comprising 1500 individuals&#44; the prevalence of dyslipidemia defined as total cholesterol &#8805;190 mg&#47;dl&#44; was 68&#46;5&#37; with 71&#37; of the individuals having LDL cholesterol &#8805;115 mg&#47;dl&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">7</span></a> The HIPOCRATES study&#44; including 1585 individuals representative of the Portuguese population aged 18&#8211;75 years old&#44; revealed a prevalence of total cholesterol &#8805;190 mg&#47;dl or the use of lipid lowering drugs of 56&#37; and a prevalence of LDL cholesterol &#8805;115 mg&#47;dl of 41&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">8</span></a> The largest epidemiological study published to date with information concerning risk factors&#44; especially dyslipidemia&#44; in a primary care setting in Portugal&#44; was the VALSIM study&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">9</span></a> It assessed 16<span class="elsevierStyleHsp" style=""></span>856 patients followed in primary care and concluded that 47&#37; had total cholesterol &#8805;200 mg&#47;dl and 38&#46;4&#37; had a LDL cholesterol &#8805;130 mg&#47;dl&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">9</span></a> More recently&#44; the eCOR study showed that 31&#46;5&#37; of the participants had LDL cholesterol &#8805;160 mg&#47;dl and 51&#46;5&#37; &#8805;130 mg&#47;dl&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">6</span></a> These studies share a factor in common&#58; cholesterol &#40;more specifically LDL cholesterol thresholds&#41; was not adjusted for the baseline cardiovascular risk&#44; possibly underestimating the prevalence of dyslipidemia burden and control&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the major Portuguese studies on dyslipidemia&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding cardiovascular events&#44; the Atlas of the European Society of Cardiology &#40;ESC&#41; showed that Portugal had an age-standardized incidence &#40;435 per 100<span class="elsevierStyleHsp" style=""></span>000 inhabitants&#41; and prevalence &#40;4871 per 100<span class="elsevierStyleHsp" style=""></span>000 inhabitants&#41; of cardiovascular disease&#46; This included atherosclerotic and non-atherosclerotic cardiovascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">10</span></a> From these&#44; the incidence &#40;83 per 100<span class="elsevierStyleHsp" style=""></span>000 inhabitants&#41; and prevalence &#40;1325 per 100<span class="elsevierStyleHsp" style=""></span>000 inhabitants&#41; of ischemic heart disease were relatively low among all ESC member countries&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">10</span></a> despite the average of 362 primary percutaneous coronary interventions per million of inhabitants&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">10</span></a> Stroke estimates &#40;incidence 76 and prevalence 804 per 100<span class="elsevierStyleHsp" style=""></span>000 inhabitants&#41; were lower than ischemic heart disease&#44; but Portugal&#39;s ranking in comparison with other ESC member countries was not so favorable&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">One of the most comprehensive studies evaluating the epidemiological data of atherosclerotic cardiovascular disease in Portugal<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">11</span></a> estimated that in 2016 about 674<span class="elsevierStyleHsp" style=""></span>000 individuals had atherothrombotic disease and that 15<span class="elsevierStyleHsp" style=""></span>000 deaths were attributable to this condition &#40;approximately 14&#37; of all-cause mortality&#41;&#44; illustrating the importance of atherosclerosis in Portugal&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">11</span></a></p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Scope and methodology of consensus</span><p id="par0055" class="elsevierStylePara elsevierViewall">An expert panel was established to gather consensus on areas of uncertainty in polypill applicability and supported by scientific evidence&#46; It involved a multidisciplinary panel of clinicians&#44; with expertise in cardiovascular prevention&#44; representing several specialties&#58; Primary Care&#44; Cardiology&#44; Neurology&#44; Internal Medicine and Clinical Pharmacology&#46; The authors conducted a literature review on Pubmed with the key words &#8220;polypill&#8221;&#44; &#8220;cardiovascular disease&#8221;&#44; &#8220;cardiovascular prevention&#8221; and &#8220;CNIC&#8221;&#44; for Centro Nacional de Investigaciones Cardiovasculares &#40;CNIC&#41;&#44; and selected all the review articles&#44; randomized controlled trials&#44; systematic reviews and meta-analysis&#46; Bibliography was shared for individual reflection&#46; All the experts contributed to the most relevant topics in their areas of expertise&#44; and a discussion meeting was held&#46; A draft of the document was produced and reviewed by all authors for final consensus&#46; Ferrer Laboratories supported the meeting and the medical writing but had no participation in the discussion or drafting of the document&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">The polypill concept</span><p id="par0060" class="elsevierStylePara elsevierViewall">The acknowledgment of the importance of cardiovascular risk factors in global morbidity and mortality&#44; and the evidence of cardiovascular event risk reduction with drug therapy&#44; led to a meeting between representatives of the Welcome Trust and the World Health Organization in 2001 to establish the principles and requirements of a single pill combination for cardiovascular prevention&#46; The potential benefits of this cardiovascular polypill&#44; at that time combining a statin&#44; a blood pressure drug&#44; aspirin&#44; and folic acid&#44; were raised by Yusuf in 2002&#44;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">12</span></a> and proposed by Wald and Law in 2003&#46; They claimed that it could theoretically reduce the population risk of cardiovascular events by at least 80&#37;&#46; These measures were the most important in the development of the concept of polypill for cardiovascular risk reduction in the population&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">13</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The cardiovascular polypill is a fixed dose combination of drugs with proven benefits in the prevention of cardiovascular disease&#44; usually a statin and a blood pressure drug&#40;s&#41;&#44; with or without aspirin&#46; The concept of the polypill was first approved in 2011 with a single pill containing aspirin&#44; ramipril&#44; and simvastatin&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">14</span></a> The candidate drugs had to warrant stability testing for all components together&#44; preserve their pharmacokinetics &#40;bioavailability&#41;&#44; pharmacodynamics &#40;the effects on blood pressure&#44; LDL cholesterol&#44; and platelet function&#41; and ideally influence &#8220;hard&#8221; cardiovascular outcomes&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Currently there are various polypills available or being investigated&#46; In Portugal&#44; only the combination of aspirin&#8211;ramipril&#8211;atorvastatin &#40;also termed CNIC-polypill&#41; and perindopril&#8211;amlodipine&#8211;atorvastatin are available &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<elsevierMultimedia ident="tb0005"></elsevierMultimedia></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Pros and cons of a cardiovascular polypill</span><p id="par0080" class="elsevierStylePara elsevierViewall">Polypills have both advantages and disadvantages for patients&#44; health care professionals and healthcare systems &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; The main advantage is the simplification of the drug treatment regimen&#44; which can lead to increase in patient compliance&#44; enhanced patient preferences&#44; fewer medication errors&#44; and thus an increase in the likelihood of reaching the target values for blood pressure and LDL cholesterol&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">15</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Another possible advantage is the potential combination of the polypill components&#46; In a pharmacodynamic open-label study&#44; Juanatey et al&#46; found that the CNIC-polypill was associated with an additional 7&#37; decrease in LDL cholesterol in comparison with the equivalent dose of isolated atorvastatin alone in a per-protocol analysis of the study&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">16</span></a> The absolute reduction in LDL cholesterol was small &#40;4&#46;7 mg&#47;dl&#41;&#44; but the relative reduction &#40;7&#37;&#41; was similar to doubling the statin dose&#46; Despite reservations regarding the methodological limitations and the clinical relevance of this LDL cholesterol decrease&#44; a synergistic effect cannot be ruled out&#44; as this phenomenon has even been described in prior studies evaluating metabolic and endothelial parameters&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">17&#8211;19</span></a> Furthermore the use of both ACE inhibitors and statins have demonstrated benefits in clinical outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">19</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The main disadvantage of the polypill is related to a less flexible dose adjustment of individual drug components&#46; If necessary&#44; this can be overcome by adding the additional medication needed&#46; On the other hand when patients start to use drugs that increase the concentration of one or more of the compounds of the polypill&#44; the potential dose adjustment requires a new prescription due to being a single compound&#46; Similarly&#44; the use of these drugs in elderly patients and those with conditions with decreased excretion of any of the compounds should be tightly monitored&#46; Other disadvantages are related to missing doses and treatment discontinuation&#44; implying missing or discontinuation of multiple drugs at the same time&#44; or even neglecting other non-pharmacological risk reduction intervention&#46; However&#44; results of clinical trials do not confirm this hypothetical disadvantage&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">20</span></a> Other potential advantages and disadvantages are shown in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">The difficulty in selecting polypill components makes it unsuitable for some types of patients&#46; Certain drugs might not be indicated or tolerated by specific patients&#46; This may be perceived as a disadvantage of the polypill&#46; Currently&#44; the most controversial components are antiplatelets agents for patients in primary prevention and beta-blockers&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Aspirin &#40;or clopidogrel in the event of intolerance&#41; is recommended by ESC guidelines for the secondary prevention of cardiovascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">21</span></a> The same guidelines recommend against antiplatelet therapy in individuals with low or moderate cardiovascular risk due to the potentially hazardous risk-benefit balance&#44; namely due to increased risk of major bleeding&#46; Nevertheless&#44; the use of aspirin may be considered in patients with diabetes in primary prevention in those with high or very high cardiovascular risk&#44; in the absence of contraindications&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">21&#44;22</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In Portugal&#44; among the two available cardiovascular polypills&#44; neither of them includes a beta blocker and one contains aspirin&#44; which implies that prescribing should be tailored according to the previously mentioned criteria&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Consensus position&#58; the simplification of the treatment regimen with a polypill&#44; can lead to an increase in patient compliance&#44; and better control of cardiovascular risk factors&#44; namely LDL-C and blood pressure levels&#46; The main disadvantage of the polypill may be the interruption of multiple drugs in the event of polypill discontinuation&#44; and the inclusion of an antithrombotic in the polypill when used in a low risk primary prevention setting&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Polypill and treatment compliance&#44; patient satisfaction&#44; and quality of life</span><p id="par0115" class="elsevierStylePara elsevierViewall">As previously mentioned&#44; one of the main advantages of the polypill is the simplification of drug therapy&#44; which can increase compliance&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">23</span></a> The problem of non-is estimated to affect about 40&#8211;50&#37; of the patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">23&#8211;25</span></a> and is estimated to be responsible for 13 of every 100<span class="elsevierStyleHsp" style=""></span>000 CVD deaths per year&#44; and approximately 9&#37; of all cardiovascular disease cases in Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">24</span></a> It is also worth noting that in secondary prevention there is an increased risk of recurrence of major adverse cardiovascular events according to the level of adherence&#44; with those who do not adhere having the highest event rates&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">26</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Four major studies were published supporting the hypothesis that polypill increases adherence to drug therapy&#46; Three of them&#44; UMPIRE&#44;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">27</span></a> IMPACT<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">28</span></a> and Kanyini-GAP&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">29</span></a> evaluated the use of the polypill vs&#46; standard of care &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44; and were pooled into the SPACE individual patient data meta-analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">15</span></a> The other study was the FOCUS project&#44; which had a first phase to determine the prevalence of non-compliance and its main determinants&#44; and a second phase which was a randomized controlled trial that allocated patients to polypill or to the separate components of the polypill &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">25</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">These studies were randomized controlled trials with an open-label design&#44; possibly increasing the risk of bias for efficacy and safety analysis&#44; but their design was adequate for compliance assessment&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The SPACE meta-analysis included 3140 patients and showed that the polypill patients had a compliance &#40;defined as taking the drugs &#8805;4 days in the last week at 12 months of follow-up&#41; of 80&#37; compared to 50&#37; in standard of care&#44; corresponding to a significant increase of 58&#37; in compliance &#40;RR 1&#46;58&#44; 95&#37; confidence interval &#40;CI&#41; 1&#46;32&#8211;1&#46;90&#41;&#46; Patients undertreated at the baseline showed an early decrease in compliance rates but overall&#44; the improvement in compliance was greater at long-term in this subgroup&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The FOCUS project further strengthened the concept of polypill as a compliance enhancer against the prescription&#47;administration of each drug component separately&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">25</span></a> Furthermore&#44; using the validated Morisky-Green questionnaire&#44; FOCUS concluded that younger patients&#44; those with depression&#44; or with complex medication regimens&#44; and those with a lower level of social support were less compliant&#44; making these subgroups the most likely to benefit from polypill when indicated&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The main drawback of the completed randomized controlled trials evaluating polypill compliance&#44; was in trying to establish a direct relationship between increased compliance and effective event reduction in the same trial&#46; This might be related to the low number of events and short follow-up period&#44; making it difficult to detect such differences&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The AURORA was a Spanish multicentric&#44; cross-sectional study that provided information about treatment satisfaction&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">30</span></a> Using the Treatment Satisfaction Questionnaire for Medication 9 items &#40;TSQM9&#41;&#44; investigators found that polypill was associated with higher satisfaction and consistently with higher compliance&#44; compared to patients receiving each drug component individually&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">30</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The pooled data analysis of UMPIRE&#44;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">27</span></a> IMPACT<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">28</span></a> and Kanyini-GAP<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">29</span></a> in the Cochrane Systematic Review published in 2017 showed no difference of polypill <span class="elsevierStyleItalic">versus</span> standard of care regarding quality of life measured by the EQ-5D scale&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">31</span></a><elsevierMultimedia ident="tb0025"></elsevierMultimedia></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Evidence for polypill in primary prevention of atherosclerotic cardiovascular disease</span><p id="par0160" class="elsevierStylePara elsevierViewall">The main evidence on the polypill in primary prevention derives from three trials &#8211; TIPS-3&#44; HOPE-3&#44; and PolyIran &#40;subgroup of patients without cardiovascular disease&#41; &#8211; which are summarized in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">32&#8211;34</span></a> The TIPS-3 and HOPE-3 trials compared the polypill with matching placebos and in the Polyran study the control was &#8220;minimal care&#8221;&#44; which did not include pharmacologic therapy&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">These data were aggregated in a systematic review with individual patient data meta-analysis&#44;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">35</span></a> including 18 182 primary prevention patients&#44; with a mean age of 63&#46;0 years&#44; a proportion of men of 50&#46;2&#37;&#44; 63&#37; with arterial hypertension&#44; 19&#37; with diabetes&#44; and 23&#37; of smokers&#46; The mean baseline LDL was 121&#46;7 mg&#47;dl&#44; the mean blood pressure was 137&#46;7&#47;81&#46;5 mmHg and mean fasting plasma glucose was 105&#46;7 mg&#47;dl&#46; The median follow-up was five years&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">35</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The estimates of this meta-analysis are depicted in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#44; with significant risk reductions of major adverse cardiovascular events &#40;MACE&#41; and each of its individual components comprising cardiovascular death&#44; myocardial infarction&#44; stroke&#44; or arterial revascularization&#46; The number needed to treat &#40;NNT&#41; to prevent one MACE with the polypill was 52 in five years&#44; being lower in the polypill with aspirin with a NNT of 37 in five years&#46; The polypill showed increased risk of muscle pain and dizziness&#44; but the proportion of gastrointestinal bleeding was not significantly increased &#40;calculated number need to harm of 554&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">35</span></a></p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">Also in primary prevention&#44; the open-label VULCANO trial randomized 492 patients at high or very high cardiovascular risk for usual care or CNIC-polypill and found that the latter significantly decreased the LDL level by 8&#46;48 mg&#47;dl and provided more 8&#46;8&#37; patients with LDL levels on target compared with usual care&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">36</span></a> VULCANO did not show non-inferiority of CNIC-polypill for blood pressure reduction or blood pressure control&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">36</span></a><elsevierMultimedia ident="tb0030"></elsevierMultimedia></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Evidence for a polypill in secondary prevention of atherosclerotic cardiovascular disease</span><p id="par0185" class="elsevierStylePara elsevierViewall">For secondary prevention of cardiovascular disease &#40;known and established atherosclerotic disease&#41;&#44; in addition to lifestyle changes&#44; drug therapy with antithrombotics and comprehensive cardiovascular risk factor control are the mainstay to decrease the recurrence of atherosclerotic cardiovascular events&#46; This is applicable for patients with coronary&#44; cerebrovascular&#44; or peripheral artery disease&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The effectiveness of polypill treatment in secondary prevention in Spain was recently evaluated in the Neptuno Study&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">37</span></a> This was a real world retrospective non-interventional study using a propensity match scoring with 23 prespecified variables&#44; establishing four cohorts with comparable baseline characteristics&#46; A total of 6546 patients were distributed in cohort 1&#44; CNIC-polypill&#59; cohort 2&#44; with the same drugs in separated monocomponents&#59; cohort 3&#44; equipotent monocomponents&#59; and cohort 4&#44; other monocomponents&#46; The main outcome was the cumulative incidence of MACE &#40;acute myocardial infarction&#44; angina&#44; ischemic stroke&#44; transient ischemic attack&#44; peripheral artery disease&#44; claudication&#44; ischemia&#44; amputation and cardiovascular mortality&#41; at 2 years follow-up&#46; The CNIC-polypill cohort was associated with a reduction of LDL cholesterol and blood pressure compared with other cohorts&#46; There was also an association with decreased MACE risk and time to event risk in the polypill cohort compared with cohorts 2 &#40;HR 0&#46;76&#59; IC95&#37; 0&#46;66&#8211;0&#46;88&#41;&#44; 3 &#40;HR 0&#46;82&#59; IC95&#37; 0&#46;71&#8211;0&#46;94&#41; and 4 &#40;HR 0&#46;83&#59; IC95&#37; 0&#46;72&#8211;0&#46;95&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The recently published Secure triale was a phase 3&#44; controlled clinical trial that assigned 2499 patients with myocardial infarction within the previous six months in seven European countries&#46; Patients were randomized to a polypill-based strategy or usual care&#46; Follow-up had a median of 36 months&#46; in seven European countries&#46; Mean age was 76&#44; with almost 60&#37; over 75 years old&#46; The majority were men&#44; 57&#37; had diabetes and 51&#37; smokers&#46; The primary composite outcome &#40;cardiovascular death&#44; nonfatal type 1 myocardial infarction&#44; nonfatal ischemic stroke&#44; or urgent revascularization&#41; was reduced 24&#37; &#40;HR ratio&#44; 0&#46;76&#59; 95&#37; confidence interval &#91;CI&#93;&#44; 0&#46;60&#8211;0&#46;96&#59; p&#61;0&#46;02&#41;&#46; The key secondary end point&#44; a composite of cardiovascular death&#44; nonfatal type 1 myocardial infarction&#44; or nonfatal ischemic stroke had also a 30&#37; risk reduction &#40;hazard ratio&#44; 0&#46;70&#59; 95&#37; CI&#44; 0&#46;54&#8211;0&#46;90&#59; p&#61;0&#46;005&#41;&#46; Adherence to medication was higher in the polypill group than in the usual care group at two years follow-up&#46; Adverse events were similar between groups and the management of dyslipidemia and hypertension was similar in both groups&#46; The reduction in events could be in part due to the pleiotropic effect of statins and angiotensin-converting-enzyme &#40;ACE&#41; inhibitors related with greater adhesion or also due to greater adhesion to aspirin in the polypill arm&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">37</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Together with to the Neptuno &#40;an observational&#41; study&#44; the evidence to supporting the polypill as an option for reducing events in secondary prevention is now growing&#46; To our knowledge&#44; no randomized evidence exists on the use of the polypill for secondary prevention in cerebrovascular or peripheral artery disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">32&#8211;34</span></a><elsevierMultimedia ident="tb0010"></elsevierMultimedia></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Populations of interest for the polypill and recommendations</span><p id="par0210" class="elsevierStylePara elsevierViewall">There are some phenotypes of patients that could derive greater benefit from the use of the polypill&#46; The identification of these subpopulations has to crossmatch patients&#8217; characteristics with their estimated cardiovascular risk&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The type of patients that are more likely to benefit from the polypill are&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0220" class="elsevierStylePara elsevierViewall">Younger patients that may be less compliant with complex regimens &#40;according to the FOCUS study&#41;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">25</span></a>&#59;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0225" class="elsevierStylePara elsevierViewall">Patients that are treatment-na&#239;ve and are simultaneously recognized as eligible for these drugs&#59;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0230" class="elsevierStylePara elsevierViewall">Asymptomatic patients with cardiovascular risk factors and suspected vascular disease &#40;for example&#58; patients with positive treadmill stress test for myocardial ischemia&#44; in addition to risk factors that increase the likelihood of the presence of coronary artery disease&#41;&#59;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0235" class="elsevierStylePara elsevierViewall">Non-adherent patients&#44; regardless of age&#59;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0240" class="elsevierStylePara elsevierViewall">Patients with difficulty in swallowing multiple pills &#40;e&#46;g&#46;&#44; some post-stroke patients with mild dysphagia&#41;&#59;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0245" class="elsevierStylePara elsevierViewall">Primary prevention patients with diabetes at high cardiovascular risk due to additional risk factors&#44; especially those with body mass index over 30 kg&#47;m<span class="elsevierStyleSup">2</span> in whom aspirin was deemed to be more beneficial in the ASCEND trial&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">39</span></a></p></li></ul></p><p id="par0250" class="elsevierStylePara elsevierViewall">The type of polypill suitable for these patients will depend on cardiovascular risk&#44; as per the Cardiovascular Prevention Guidelines<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">21</span></a>&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0255" class="elsevierStylePara elsevierViewall">Moderate Risk &#8211; it is reasonable to prescribe a polypill without aspirin to control the cardiovascular risk factors&#44; and HOPE-3 trial supports this recommendation&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">33</span></a></p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0260" class="elsevierStylePara elsevierViewall">High or very high risk &#8211; patients might be eligible for the polypill with or without aspirin&#46;</p></li></ul></p><p id="par0265" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a> summarizes the polypill options based on patient characteristics and CV risk&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0270" class="elsevierStylePara elsevierViewall">It is also important to determine if polypill prescription leads to the reaching of risk factor control targets&#44; with or without additional drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">21</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">The prescription of the polypill needs to weigh up the benefits and risks and&#44; whenever possible&#44; the patient should be involved in the decision process&#44; stressing the importance of compliance&#46;<elsevierMultimedia ident="tb0015"></elsevierMultimedia></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Pharmacoeconomics</span><p id="par0285" class="elsevierStylePara elsevierViewall">Cardiovascular disease &#40;including ischemic heart disease and stroke&#41; is the foremost cause of disease burden worldwide according to the GBD 2019 Disease and Injuries report&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">40</span></a> The importance of atherosclerotic disease in Portugal was further stressed in the reports on the national cost and burden of atherosclerosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">11&#44;41</span></a> In 2016&#44; atherosclerosis was responsible for 14&#46;3&#37; of overall mortality and for 260<span class="elsevierStyleHsp" style=""></span>943 cisability-adjusted life years&#44; of which 75&#37; of them were due to premature death and 25&#37; to disability&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">41</span></a> Atherosclerosis was estimated to yield costs equivalent of 1&#37; of the Portuguese gross domestic product and 11&#37; of the health expenditures in the same year&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">41</span></a> This emphasizes that potential beneficial interventions may be valuable not only for patients but for all stakeholders&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">Regarding polypill cost-effectiveness&#44; the available reports support that the cardiovascular polypill is cost-effective using different models and data from different countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">42&#8211;47</span></a> Being cost-effective translates into gains in health for the population with an acceptable cost for the healthcare system&#44; usually expressed in incremental cost-effectiveness ratio &#40;ICER&#41; per quality adjusted life years &#40;QALY&#41;&#46; There are some published models with different polypills&#46; Wald and Jowett evaluated a polypill with statin and three low-dose anti-hypertensive drugs &#40;ACE inhibitor&#47;angiotensin receptor blocker&#44; hydrochlorothiazide and amlodipine&#41; as a primary prevention strategy in the United Kingdom in two different pharmacoeconomic studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">43&#44;47</span></a> Both included the potential benefits of cardiovascular events due to control of risk factors but only Wald considered the potential benefits of increased compliance&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">43&#44;47</span></a> The other cost-effective studies &#40;with scenarios for United Kingdom&#44; United States of America&#44; and other countries such as China&#44; India&#44; Mexico&#44; Nigeria&#44; and South Africa&#44; as well as models for low-income and middle-income countries&#41; evaluated aspirin-containing polypills with or without beta-blockers&#44; mostly in secondary prevention and used estimates for risk reduction of cardiovascular events due to risk factors improvement and increased treatment compliance&#46;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">42&#44;44&#8211;46</span></a> In both primary and secondary prevention scenarios these models supported the polypill strategy as &#8216;cost-effective&#8217;&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">For the Portuguese scenario&#44; the aspirin-containing polypill cost-effectiveness was evaluated for patients with established coronary disease and for post-stroke patients &#40;the Mercury Study&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">48</span></a> Using a Markov model&#44; the authors compared the polypill with monocomponents over a lifetime horizon and from the perspective of the Portuguese national healthcare system&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">48</span></a> Patient characteristics were derived from the Portuguese Registry of Acute Coronary Syndromes subgroup that had previous history of coronary disease&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">49</span></a> The evaluation for post-ischemic stroke patients&#44; followed the same methodology&#44; but the patients characteristics were derived from the Central Administration of the Portuguese Health System&#44; and the polypill was cost-effective with an ICER of &#8364;2353&#47;QALY&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">50</span></a> The treatment effects of the polypill and monocomponents were extrapolated from the Spanish retrospective real world NEPTUNO study&#44; which found differences in the lipid and blood pressure profiles of polypill vs&#46; separate monocomponents&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">51</span></a> In the Mercury study&#44; the incremental cost-utility ratio was &#8364;1557&#47;QALY gained&#46; Assuming a willingness-to-pay threshold of &#8364;30<span class="elsevierStyleHsp" style=""></span>000&#47;QALY gained&#44; there is a 79&#46;7&#37; probability of the CNIC-Polypill being cost-effective compared with the combination of monocomponents&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">48</span></a> In spite of these results&#44; it is important to highlight the limitations inherent to this analysis&#44; such as the use of clinical registries and observational data to extrapolate the pharmacoeconomic impact of the polypill&#46;<elsevierMultimedia ident="tb0020"></elsevierMultimedia></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conclusions</span><p id="par0305" class="elsevierStylePara elsevierViewall">The polypill may be useful in the prevention of cardiovascular disease by improving cardiovascular risk factors and increasing compliance with drug therapy&#46; A possible synergistic effect resulting from the combination of its components in risk factors&#8217; control cannot be excluded&#46; There are subgroups of patients that can benefit more from fixed dose combinations of drugs that aim to prevent cardiovascular events &#40;e&#46;g&#46;&#44; younger patients&#44; treatment-na&#239;ve patients&#44; or patients with diabetes&#41;&#46; The polypill has proved to improve risk factor control both in primary and secondary prevention settings and there are data supporting the use of the polypill for the reduction in cardiovascular events&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflicts of interest</span><p id="par0310" class="elsevierStylePara elsevierViewall">Ferrer laboratories supported the expert panel meeting and the medical writing but did not have any participation in the discussion or drafting of the document&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">FA has received honoraria for lecturing&#44; investigation&#44; and consulting activities from Akcea&#44; Astra Zeneca&#44; Bayer&#44; Bial&#44; Boehringer Ingelheim&#44; Daiichi Sankyo&#44; Ferrer&#44; Jaba&#44; Lilly&#44; Menarini&#44; Medinfar&#44; MSD&#44; Novartis&#44; Novo Nordisk&#44; Servier&#44; Tecnifar&#44; Tecnimede&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">DC has participated in educational meetings and&#47;or attended a conferences or symposia &#40;including travel&#44; accommodation and&#47;or hospitality in the last 5 years&#41; with Bristol-Myers Squibb&#44; Bayer&#44; Boehringer Ingelheim&#44; Daiichi Sankyo&#44; Menarini&#44; Merck Serono&#44; Ferrer&#44; Pfizer&#44; Novartis and Roche&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">CA has received honoraria for consultancy from Ferrer&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">JPA nothing to declare&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall">NC has received honoraria for consultancy from Ferrer&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">VC participated in educational meetings and received honoraria for lecturing and consulting activities from Bial&#44; Ferrer&#44; Jaba&#44; Medicamenta&#44; Medinfar and Servier&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">LF has received honoraria for lecturing&#44; investigation&#44; and consulting activities from Boehringer Ingelheim and Novo Nordisk&#59; has participated in educational meetings and&#47;or attended a conferences or symposia &#40;including travel&#44; accommodation and&#47;or hospitality&#41; with Bayer&#44; Boehringer Ingelheim&#44; Daiichi Sankyo&#44; Ferrer&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">JPM has received honoraria for lecturing&#44; investigation&#44; and consulting activities from Amgen&#44; Astrazeneca&#44; Bayer&#44; Bial&#44; Boehringer Ingelheim&#44; Ferrer&#44; MSD&#44; Takeda&#44; Tecnimede&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">VPD has received honoraria for lecturing&#44; and consulting activities from Delta&#44; JABA&#44; Servier&#44; Tecnimede&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">HR has received honoraria for consultancy from Ferrer&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">VTC has received honoraria for lecturing&#44; investigation&#44; and consulting activities from Bayer&#59; Boehringer Ingelheim&#59; Biogen Idec&#59; Bioportugal&#59; Bristol Meyers Squibb&#47;Pfizer&#59; Roche&#59; Novartis&#59; Abbott&#59; Ferrer&#59; Astra Zeneca&#59; PHRI&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">CG has received honoraria for lecturing&#44; investigation&#44; and consulting activities from AstraZeneca&#44; Bayer&#44; Bial&#44; Boehringer Ingelheim&#44; Daiichi Sankyo&#44; Ferrer&#44; Lilly&#44; MSD&#44; Novartis&#44; Novo Nordisk and Servier&#46;</p></span></span>"
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          "titulo" => "Background"
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              "identificador" => "sec0010"
              "titulo" => "Cardiovascular disease"
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              "identificador" => "sec0015"
              "titulo" => "Hypertension&#44; dyslipidemia and atherothrombosis in Portugal"
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          "identificador" => "sec0020"
          "titulo" => "Scope and methodology of consensus"
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          "identificador" => "sec0025"
          "titulo" => "The polypill concept"
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        7 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Pros and cons of a cardiovascular polypill"
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        8 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Polypill and treatment compliance&#44; patient satisfaction&#44; and quality of life"
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          "identificador" => "sec0040"
          "titulo" => "Evidence for polypill in primary prevention of atherosclerotic cardiovascular disease"
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          "titulo" => "Evidence for a polypill in secondary prevention of atherosclerotic cardiovascular disease"
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          "identificador" => "sec0050"
          "titulo" => "Populations of interest for the polypill and recommendations"
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          "titulo" => "Pharmacoeconomics"
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    "fechaAceptado" => "2023-02-12"
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          "clase" => "keyword"
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            1 => "Cardiovascular"
            2 => "Prevention"
            3 => "Consensus"
            4 => "Primary"
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            1 => "Cardiovascular"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular &#40;CV&#41; guidelines stress the need for global intervention to manage risk factors and reduce the risk of major vascular events&#46; Growing evidence supports the use of polypill as a strategy to prevent cerebral and cardiovascular disease&#44; however it is still underused in clinical practice&#46; This paper presents an expert consensus aimed to summarize the data regarding polypill use&#46; The authors consider the benefits of polypill and the significant claims for clinical applicability&#46; Potential advantages and disadvantages&#44; data regarding several populations in primary and secondary prevention&#44; and pharmacoeconomic data are also addressed&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">As recomenda&#231;&#245;es cardiovasculares salientam a necessidade de uma interven&#231;&#227;o global para controlar os fatores de risco e assim reduzir o risco de eventos vasculares <span class="elsevierStyleItalic">major</span>&#46; H&#225; evid&#234;ncia crescente que apoia o uso da polip&#237;lula como estrat&#233;gia de preven&#231;&#227;o de doen&#231;as c&#233;rebro e cardiovasculares&#44; por&#233;m esta ainda &#233; subutilizada na pr&#225;tica cl&#237;nica&#46; Este artigo apresenta um consenso de especialistas com o objetivo de resumir os dados sobre a utiliza&#231;&#227;o de polip&#237;lula&#46; Os autores consideram os benef&#237;cios da polip&#237;lula e a sua poss&#237;vel aplicabilidade cl&#237;nica&#46; Vantagens e desvantagens potenciais&#44; dados referentes a popula&#231;&#245;es em preven&#231;&#227;o prim&#225;ria e secund&#225;ria e dados f&#225;rmaco-econ&#243;micos tamb&#233;m s&#227;o abordados&#46;</p></span>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Potential advantages and disadvantages of the Polypill strategy for the different stakeholders&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Polypill eligibility according to the patients&#8217; profile and cardiovascular risk&#46; ACS&#58; acute coronary syndrome&#59; CCS&#58; chronic coronary syndrome&#59; CTA&#58; computerized tomographic angiography&#59; CKD&#58; chronic kidney disease&#59; CV&#58; cardiovascular&#59; DM&#58; diabetes&#59; eGFR&#58; estimated glomerular filtration rate&#59; FH&#58; familial hypercholesterolemia&#59; HTN&#58; hypertension&#59; ICA&#58; invasive coronary angiography&#59; MA&#58; microalbuminuria&#59; PAD&#58; peripheral arterial disease SCORE&#58; Systematic Coronary Risk Estimation for cardiovascular mortality at 10 years&#59; TIA&#58; transient ischemic attack&#59; TOD&#58; target organ damage&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Key studies on hypertension prevalence in Portugal</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study period&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prevalence of hypertension&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control of hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">PAP<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">4</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2003&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">42&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">11&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">PHYSA<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">5</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2011&#8211;2012&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">42&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">e&#95;COR<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">6</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2012&#8211;2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3295223.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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Key studies of dyslipidemia prevalence in Portugal</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study period&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prevalence of elevated total cholesterol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prevalence of elevated LDL cholesterol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BECEL<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">7</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;190 mg&#47;dl&#58; 68&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;115 mg&#47;dl&#58; 71&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VALSIM<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">9</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2006&#8211;2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;200 mg&#47;dl&#58; 47&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;130 mg&#47;dl&#58; 38&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HIPOCRATES<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">8</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;190 mg&#47;dl&#58; 56&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;115 mg&#47;dl&#58; 41&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">e&#95;COR<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">6</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2012&#8211;2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;200 mg&#47;dl&#58; 56&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;130 mg&#47;dl&#58; 51&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3295224.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Key studies on the prevalence of hypertension and dyslipidemia in Portugal&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cardiovascular polypills currently available in Portugal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Studied polypills currently not available in Portugal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CNIC polypill&#58; aspirin&#44; ramipril and atorvastatin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aspirin&#44; simvastatin&#44; atenolol&#44; thiazide and ramipril&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Perindopril&#44; amlodipine&#44; and atorvastatin</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aspirin&#44; losartan&#44; atenolol&#44; and atorvastatin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clopidogrel&#44; Atorvastatin&#44; and ramipril&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aspirin&#44; Ramipril&#44; metoprolol&#44; and atorvastatin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aspirin&#44; atorvastatin&#44; hydrochlorothiazide&#44; and&#44; valsartan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aspirin&#44; atorvastatin&#44; hydrochlorothiazide&#44; and enalapril&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amlodipine&#44; rosuvastatin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pitavastatin&#42;&#44; valsartan<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ramipril&#44; hydrochlorothiazide&#44; atenolol&#44; simvastatin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Polypills under investigation or with market approval based on Webster et al&#46;&#44; 2017&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">14</span></a></p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
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        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Trials&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Population&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Polypill&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UMPIRE<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2004 patients with established CVD or at risk of CVD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aspirin 75 mg&#44; simvastatin 40 mg&#44; lisinopril 10 mg&#44; and atenolol 50 mg or hydrochlorothiazide 12&#46;5 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Polypill significantly improved medication adherence by 33&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IMPACT<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">513 patients at high CV risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aspirin 75 mg&#44; simvastatin 40 mg&#44; lisinopril 10 mg&#44; and atenolol 50 mg or hydrochlorothiazide 12&#46;5 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Polypill significantly improved medication adherence by 75&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kanyini-GAP<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">623 patients with established CVD or at risk of CVD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aspirin 75 mg&#44; simvastatin 40 mg&#44; lisinopril 10 mg&#44; and atenolol 50 mg or hydrochlorothiazide 12&#46;5 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Polypill significantly improved medication adherence by 49&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FOCUS Phase 2<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">695 at secondary prevention after MI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aspirin 100 mg&#44; simvastatin 40 mg&#44; and ramipril 2&#46;5&#44; 5&#44; or 10 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Polypill significantly improved medication adherence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Main characteristics of randomized controlled trials that evaluated the compliance with the polypill&#46;</p>"
        ]
      ]
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        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
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            "identificador" => "at4"
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        "tabla" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristic&#47;trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TIPS-3<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HOPE-3<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PolyIran<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiplatelet component&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aspirin 75 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No antiplatelet component&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aspirin 81 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lipid lowering component&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Simvastatin 40 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rosuvastatin 10 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">atorvastatin 20 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blood pressure lowering component&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ramipril 10 mgAtenolol 100 mgHydrochlorothiazide 25 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Candesartan 16 mg Hydrochlorothiazide 12&#46;5 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Enalapril 5 mg or valsartan 40 mgHydrochlorothiazide 12&#46;5 mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Number of patients included in the trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5713&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6348&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6101&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Men&#8805;50 years and women&#8805;55 years with an INTERHEART risk score&#8805;10&#44; or men and women&#8805;65 years with an INTERHEART risk score of &#8805;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Men&#8805;55 years or women&#8805;65 with at least one of the following cardiovascular risk factors&#58; elevated waist-to-hip ratio&#44; history of a low level of high-density lipoprotein cholesterol&#44; current or recent tobacco use&#44; hyperglycemia&#44; family history of premature coronary disease&#44; and mild renal dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age 50&#8805;years&#44; living in rural areas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Trial design&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Randomized double-blinded placebo-controlled trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Randomized double-blinded placebo-controlled trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cluster randomized controlled trial&#44; with stratification by districts and using villages as the unit of clustering for randomization &#40;236 clusters&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Comparator&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Matching placebos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Matching placebos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Minimal care &#40;blood pressure measurement and risk factor counselling&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Main conclusions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Polypill with aspirin reduced the incidence of cardiovascular events in persons at intermediate cardiovascular risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rosuvastatin&#44; candesartan and hydrochlorothiazide reduced the risk of cardiovascular events in persons at intermediate risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Polypill reduced major cardiovascular events with high medication adherence and low incidence of adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Summary characteristics of randomized controlled trials that evaluated the polypill in primary prevention of atherosclerotic cardiovascular disease&#46;</p>"
        ]
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      6 => array:8 [
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        "etiqueta" => "Table 5"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">CI&#58; confidence interval&#59; HR&#58; hazard ratio&#59; MACE&#58; major adverse cardiovascular events &#40;cardiovascular death&#44; non-fatal myocardial infarction&#44; non-fatal stroke&#44; revascularization&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">32</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR &#40;95&#37;CI&#41; for polypill &#40;with or without aspirin&#41; vs control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR &#40;95&#37;CI&#41; for polypill &#40;with aspirin&#41; vs control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR &#40;95&#37;CI&#41; for polypill &#40;without aspirin&#41; vs control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MACE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;62 &#40;0&#46;53&#8211;0&#46;73&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;53 &#40;0&#46;41&#8211;0&#46;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;68 &#40;0&#46;57&#8211;0&#46;81&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiovascular mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;65 &#40;0&#46;52&#8211;0&#46;81&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;51 &#40;0&#46;37&#8211;0&#46;72&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;73 &#40;0&#46;57&#8211;0&#46;93&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Myocardial infarction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Estimates from the meta-analysis evaluating the effects of a polypill with or without aspirin on cardiovascular outcomes and all-cause mortality in primary prevention&#46;</p>"
        ]
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        "identificador" => "tb0005"
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        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0075" class="elsevierStylePara elsevierViewall">Consensus statement&#58; The authors adopted the concept of polypill as a single pill containing an antidyslipidemic drug &#40;a statin&#41;&#44; and an anti-hypertensive drug&#44; with or without an antithrombotic drug&#46;</p></span>"
        ]
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        "identificador" => "tb0025"
        "tipo" => "MULTIMEDIATEXTO"
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          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0155" class="elsevierStylePara elsevierViewall">Consensus position&#58; Polypill improves medication adherence in high risk patients both in primary as well as secondary prevention&#46; Although plausible&#44; a direct relationship between adherence due to fixed combinations and better cardiovascular outcomes has yet to be established in randomized controlled trials&#46; Higher compliance and patient satisfaction have been reported&#44; but improvement in quality of life remains to be clarified in future trials&#46;</p></span>"
        ]
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      9 => array:5 [
        "identificador" => "tb0030"
        "tipo" => "MULTIMEDIATEXTO"
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        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0180" class="elsevierStylePara elsevierViewall">Consensus statement&#58; polypill&#44; with or without aspirin&#44; improves risk factors control and cardiovascular outcomes in primary prevention&#44; reducing cardiovascular mortality and major cardiovascular events in comparison with placebo or no pharmacologic treatment&#46; The use of aspirin should be assessed in an individual basis&#44; weighting the risk of thrombosis versus the risk of bleeding&#46;</p></span>"
        ]
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        "identificador" => "tb0010"
        "tipo" => "MULTIMEDIATEXTO"
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          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0205" class="elsevierStylePara elsevierViewall">Consensus statement&#58; A cardiovascular polypill is a valid option after an atherosclerotic cardiovascular event&#44; arising from coronary&#44; cerebrovascular&#44; or peripheral arterial disease&#44; in patients with indication for the composite of the monocomponents&#44; assuming that this strategy can improve treatment adherence&#46; This is in accordance with the first stepwise approach in patients with established atherosclerotic cardiovascular disease as endorsed by the ESC 2021 Prevention Guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">38</span></a> which proposes antithrombotic therapy&#44; lipid and hypertension control and smoking cessation as the baseline strategy in the prevention of recurrent events&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">38</span></a> The SECURE trial proved the efficacy of a polypill in reducing MACE in an elderly population with a previous myocardial infarction&#46;</p></span>"
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        "tipo" => "MULTIMEDIATEXTO"
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        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0280" class="elsevierStylePara elsevierViewall">Consensus statement&#58; Patients eligible for an aspirin-containing polypill are those in secondary cardiovascular prevention and&#44; on an individual basis&#44; those at very high risk such as patients with diabetes with target organ disease and low bleeding risk&#46; Non-adherent patients&#44; younger patients&#44; and the medication-na&#239;ve are also suitable candidates for polypill use&#46;</p></span>"
        ]
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          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0300" class="elsevierStylePara elsevierViewall">Consensus statement&#58; Currently both polypills marketed in Portugal &#40;aspirin&#44; atorvastatin&#44; ramipril&#59; and perindopril&#44; amlodipine&#44; atorvastatin&#41; are reimbursed&#44; after a cost-minimization analysis that determined that the price of the fixed combinations is inferior to the sum of all individual components&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">52&#44;53</span></a></p></span>"
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      "titulo" => "References"
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        0 => array:2 [
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              "identificador" => "bib0270"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Cardiovascular diseases &#40;CVDs&#41; &#91;Internet&#93;&#46; Available from&#58; <a target="_blank" href="https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-%28cvds%29">https&#58;&#47;&#47;www&#46;who&#46;int&#47;news-room&#47;fact-sheets&#47;detail&#47;cardiovascular-diseases-&#37;28cvds&#37;29</a> &#91;cited 21&#46;10&#46;21&#93;&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries &#40;the INTERHEART study&#41;&#58; case&#8211;control study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "S&#46; Yusuf"
                            1 => "S&#46; Hawken"
                            2 => "S&#46; &#212;unpuu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(04)17018-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2004"
                        "volumen" => "364"
                        "paginaInicial" => "937"
                        "paginaFinal" => "952"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15364185"
                            "web" => "Medline"
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                ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries &#40;INTERSTROKE&#41;&#58; a case&#8211;control study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "M&#46;J&#46; O&#8217;Donnell"
                            1 => "S&#46;L&#46; Chin"
                            2 => "S&#46; Rangarajan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(16)30506-2"
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                        "tituloSerie" => "Lancet"
                        "fecha" => "2016"
                        "volumen" => "388"
                        "paginaInicial" => "761"
                        "paginaFinal" => "775"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27431356"
                            "web" => "Medline"
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                ]
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence&#44; awareness&#44; treatment and control of hypertension in Portugal&#58; the PAP study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;E&#46; Macedo"
                            1 => "M&#46;J&#46; Lima"
                            2 => "A&#46;O&#46; Silva"
                            3 => "P&#46; Alcantara"
                            4 => "V&#46; Ramalhinho"
                            5 => "J&#46; Carmona"
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                    ]
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                    0 => array:2 [
                      "doi" => "10.1097/01.hjh.0000179908.51187.de"
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                        "tituloSerie" => "J Hypertens"
                        "fecha" => "2005"
                        "volumen" => "23"
                        "paginaInicial" => "1661"
                        "paginaFinal" => "1666"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16093910"
                            "web" => "Medline"
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                      "titulo" => "Prevalence&#44; awareness&#44; treatment and control of hypertension and salt intake in Portugal"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Polonia"
                            1 => "L&#46; Martins"
                            2 => "F&#46; Pinto"
                            3 => "J&#46; Nazare"
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                      "doi" => "10.1097/HJH.0000000000000162"
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                        "tituloSerie" => "J Hypertens"
                        "fecha" => "2014"
                        "volumen" => "32"
                        "paginaInicial" => "1211"
                        "paginaFinal" => "1221"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24675681"
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                      "titulo" => "Preval&#234;ncia de fatores de risco cardiovascular na popula&#231;&#227;o portuguesa&#58; Relat&#243;rio estudo e&#95;COR"
                      "autores" => array:1 [
                        0 => array:2 [
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                            0 => "M&#46; Bourbon"
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                            2 => "Q&#46; Rato"
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                      "titulo" => "Preval&#234;ncia e caracteriza&#231;&#227;o da hipercolesterolemia em Portugal&#58; Estudo HIPOCRATES"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46; Perdig&#227;o"
                            1 => "J&#46;S&#46; Duarte"
                            2 => "A&#46; Santos"
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Revista factores de risco"
                        "fecha" => "2010"
                        "volumen" => "17"
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                          "pii" => "S0022534715049150"
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                    0 => array:2 [
                      "titulo" => "Caracteriza&#231;&#227;o do perfil lip&#237;dico nos utentes dos cuidados de sa&#250;de prim&#225;rios em Portugal"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "N&#46; Cortez-Dias"
                            1 => "S&#46; Robalo Martins"
                            2 => "A&#46; Belo"
                            3 => "M&#46; Fi&#250;za"
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                      "doi" => "10.1016/j.repc.2013.06.008"
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                        "tituloSerie" => "Revista Portuguesa de Cardiologia"
                        "fecha" => "2013"
                        "volumen" => "32"
                        "paginaInicial" => "987"
                        "paginaFinal" => "996"
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "European Society of Cardiology&#58; cardiovascular disease statistics 2021"
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Timmis"
                            1 => "P&#46; Vardas"
                            2 => "N&#46; Townsend"
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                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehab892"
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                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2022"
                        "volumen" => "43"
                        "paginaInicial" => "716"
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                    0 => array:2 [
                      "titulo" => "The burden of atherosclerosis in Portugal"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46; Costa"
                            1 => "J&#46; Alarc&#227;o"
                            2 => "F&#46; Araujo"
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                    0 => array:2 [
                      "doi" => "10.1093/ehjqcco/qcaa060"
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                        "tituloSerie" => "Eur Heart J &#8211; Qual Care Clin Outcomes"
                        "fecha" => "2021"
                        "volumen" => "7"
                        "paginaInicial" => "154"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32946553"
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                    0 => array:2 [
                      "titulo" => "Two decades of progress in preventing vascular disease"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46; Yusuf"
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                      "doi" => "10.1016/S0140-6736(02)09358-3"
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                        "tituloSerie" => "Lancet"
                        "fecha" => "2002"
                        "volumen" => "360"
                        "paginaInicial" => "2"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12114031"
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              "etiqueta" => "13"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A strategy to reduce cardiovascular disease by more than 80&#37;"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "N&#46;J&#46; Wald"
                            1 => "M&#46;R&#46; Law"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Br Med J"
                        "fecha" => "2003"
                        "volumen" => "326"
                        "paginaInicial" => "1419"
                        "paginaFinal" => "1423"
                      ]
                    ]
                  ]
                ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Putting polypills into practice&#58; challenges and lessons learned"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46; Webster"
                            1 => "J&#46;M&#46; Castellano"
                            2 => "O&#46;K&#46; Onuma"
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                        ]
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                        "paginaFinal" => "1074"
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                      "titulo" => "Effectiveness of fixed dose combination medication &#40;&#8216;polypills&#8217;&#41; compared with usual care in patients with cardiovascular disease or at high risk&#58; a prospective&#44; individual patient data meta-analysis of 3140 patients in six countries"
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                          "autores" => array:3 [
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                        "tituloSerie" => "Int J Cardiol"
                        "fecha" => "2016"
                        "volumen" => "205"
                        "paginaInicial" => "147"
                        "paginaFinal" => "156"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26736090"
                            "web" => "Medline"
                          ]
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                    0 => array:2 [
                      "titulo" => "Pharmacodynamic study of the cardiovascular polypill&#46; Is there any interaction among the monocomponents&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;R&#46; Gonz&#225;lez-Juanatey"
                            1 => "J&#46; Tamargo"
                            2 => "F&#46; Torres"
                            3 => "B&#46; Weisser"
                            4 => "N&#46; Oudovenko"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Revista Espa&#241;ola de Cardiolog&#237;a &#40;Engl Ed&#41;"
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                        "paginaInicial" => "51"
                        "paginaFinal" => "58"
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                    ]
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              ]
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              "identificador" => "bib0350"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Statins and renin&#8211;angiotensin system inhibitor combination treatment to prevent cardiovascular disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "H&#46;-Y&#46; Lee"
                            1 => "I&#46; Sakuma"
                            2 => "S&#46;-H&#46; Ihm"
                            3 => "C&#46;-W&#46; Goh"
                            4 => "K&#46;K&#46; Koh"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1253/circj.cj-13-1494"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circ J"
                        "fecha" => "2014"
                        "volumen" => "78"
                        "paginaInicial" => "281"
                        "paginaFinal" => "287"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24401609"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
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              "identificador" => "bib0355"
              "etiqueta" => "18"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Atorvastatin and quinapril inhibit blood coagulation in patients with coronary artery disease following 28 days of therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Undas"
                            1 => "K&#46;E&#46; Brummel-Ziedins"
                            2 => "D&#46;P&#46; Potaczek"
                          ]
                        ]
                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1111/j.1538-7836.2006.02165.x"
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                        "tituloSerie" => "J Thromb Haemost"
                        "fecha" => "2006"
                        "volumen" => "4"
                        "paginaInicial" => "2397"
                        "paginaFinal" => "2404"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16907931"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0360"
              "etiqueta" => "19"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "V&#46;G&#46; Athyros"
                            1 => "D&#46;P&#46; Mikhailidis"
                            2 => "A&#46;A&#46; Papageorgiou"
                          ]
                        ]
                      ]
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                  ]
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                    0 => array:2 [
                      "doi" => "10.1038/sj.jhh.1001748"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hum Hypertens"
                        "fecha" => "2004"
                        "volumen" => "18"
                        "paginaInicial" => "781"
                        "paginaFinal" => "788"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15229622"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "etiqueta" => "20"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Do polypills lead to neglect of lifestyle risk factors&#63; Findings from an individual participant data meta-analysis among 3140 patients at high risk of cardiovascular disease"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "V&#46; Selak"
                            1 => "C&#46; Bullen"
                            2 => "S&#46; Stepien"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/2047487316638216"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Prev Cardiol"
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                        "volumen" => "23"
                        "paginaInicial" => "1393"
                        "paginaFinal" => "1400"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26945024"
                            "web" => "Medline"
                          ]
                        ]
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                    ]
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                ]
              ]
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                    0 => array:2 [
                      "titulo" => "2021 ESC Guidelines on cardiovascular disease prevention in clinical practice"
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                          "autores" => array:3 [
                            0 => "F&#46;L&#46;J&#46; Visseren"
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                            2 => "Y&#46;M&#46; Smulders"
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                      ]
                    ]
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                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Prevent Cardiol"
                        "fecha" => "2022"
                        "volumen" => "29"
                        "paginaInicial" => "5"
                        "paginaFinal" => "115"
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "titulo" => "Aspirin in the primary prevention of cardiovascular disease on diabetic patients&#58; systematic review and meta-analysis"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "D&#46; Caldeira"
                            1 => "M&#46; Alves"
                            2 => "C&#46; David"
                            3 => "J&#46; Costa"
                            4 => "J&#46;J&#46; Ferreira"
                            5 => "F&#46;J&#46; Pinto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "Prim Care Diabetes"
                        "fecha" => "2020"
                        "volumen" => "14"
                        "paginaInicial" => "213"
                        "paginaFinal" => "221"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31791903"
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                        "itemHostRev" => array:3 [
                          "pii" => "S0030666514001911"
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                          "issn" => "00306665"
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                  ]
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              "identificador" => "bib0380"
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                      "titulo" => "Impacto da frequ&#234;ncia posol&#243;gica na ades&#227;o terap&#234;utica em doen&#231;as cardiovasculares cr&#243;nicas&#58; revis&#227;o sistem&#225;tica e meta-an&#225;lise"
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                        "tituloSerie" => "Revista Portuguesa de Cardiologia"
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                        "volumen" => "33"
                        "paginaInicial" => "431"
                        "paginaFinal" => "437"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25070671"
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                ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adherence to cardiovascular therapy&#58; a meta-analysis of prevalence and clinical consequences"
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                          "etal" => true
                          "autores" => array:3 [
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                            2 => "E&#46; Heydon"
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                    ]
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                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2013"
                        "volumen" => "34"
                        "paginaInicial" => "2940"
                        "paginaFinal" => "2948"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23907142"
                            "web" => "Medline"
                          ]
                        ]
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                ]
              ]
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              "identificador" => "bib0390"
              "etiqueta" => "25"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A polypill strategy to improve adherence"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46;M&#46; Castellano"
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                        ]
                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2014.08.021"
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                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2014"
                        "volumen" => "64"
                        "paginaInicial" => "2071"
                        "paginaFinal" => "2082"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25193393"
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                ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Assessing the impact of medication adherence on long-term cardiovascular outcomes"
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                    ]
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                        "volumen" => "68"
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                        "paginaFinal" => "801"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27539170"
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                ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD&#58; the UMPIRE randomized clinical trial"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
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                            2 => "J&#46; Field"
                          ]
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                      ]
                    ]
                  ]
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                    0 => array:2 [
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                        "tituloSerie" => "JAMA"
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                        "volumen" => "310"
                        "paginaInicial" => "918"
                        "paginaFinal" => "929"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24002278"
                            "web" => "Medline"
                          ]
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                ]
              ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Effect of fixed dose combination treatment on adherence and risk factor control among patients at high risk of cardiovascular disease&#58; randomised controlled trial in primary care"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
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                            2 => "C&#46; Bullen"
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                    ]
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                    0 => array:2 [
                      "doi" => "10.1136/bmj.g3318"
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                        "tituloSerie" => "BMJ"
                        "fecha" => "2014"
                        "volumen" => "348"
                        "paginaInicial" => "g3318"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24868083"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0410"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk"
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                          "etal" => true
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Prevent Cardiol"
                        "fecha" => "2015"
                        "volumen" => "22"
                        "paginaInicial" => "920"
                        "paginaFinal" => "930"
                      ]
                    ]
                  ]
                ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Evaluating patients&#8217; satisfaction and preferences with a secondary prevention cardiovascular polypill&#58; the Aurora study"
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                        0 => array:2 [
                          "etal" => false
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Compar Effect Res"
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                        "volumen" => "10"
                        "paginaInicial" => "975"
                        "paginaFinal" => "985"
                      ]
                    ]
                  ]
                ]
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            30 => array:3 [
              "identificador" => "bib0420"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases"
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                    0 => array:2 [
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                        "tituloSerie" => "Cochrane Database Syst Rev"
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                        "volumen" => "3"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28263370"
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                ]
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              "identificador" => "bib0425"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Polypill with or without aspirin in persons without cardiovascular disease"
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                            2 => "A&#46; Dans"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa2028220"
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                        "fecha" => "2021"
                        "volumen" => "384"
                        "paginaInicial" => "216"
                        "paginaFinal" => "228"
                        "link" => array:1 [
                          0 => array:2 [
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                ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Blood-pressure and cholesterol lowering in persons without cardiovascular disease"
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                            0 => "S&#46; Yusuf"
                            1 => "E&#46; Lonn"
                            2 => "P&#46; Pais"
                          ]
                        ]
                      ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1600177"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2016"
                        "volumen" => "374"
                        "paginaInicial" => "2032"
                        "paginaFinal" => "2043"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27039945"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
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                ]
              ]
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            33 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases &#40;PolyIran&#41;&#58; a pragmatic&#44; cluster-randomised trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "G&#46; Roshandel"
                            1 => "M&#46; Khoshnia"
                            2 => "H&#46; Poustchi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(19)31791-X"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2019"
                        "volumen" => "394"
                        "numero" => "10199"
                        "paginaInicial" => "672"
                        "paginaFinal" => "683"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31448738"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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            34 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease&#58; an individual participant data meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "P&#46; Joseph"
                            1 => "G&#46; Roshandel"
                            2 => "P&#46; Gao"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(21)01827-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2021"
                        "volumen" => "398"
                        "paginaInicial" => "1133"
                        "paginaFinal" => "1146"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34469765"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            35 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety and efficacy of a cardiovascular polypill in people at high and very high risk without a previous cardiovascular event the international VULCANO randomised clinical trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46;M&#46; Mostaza"
                            1 => "C&#46; Suarez-Fern&#225;ndez"
                            2 => "J&#46; Cos&#237;n-Sales"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12872-022-03013-w"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Cardiovasc Disord"
                        "fecha" => "2022"
                        "volumen" => "22"
                        "paginaInicial" => "560"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36550424"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            36 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reduction of cardiovascular events in patients with cardiovascular disease with the CV-polypill&#58; a retrospective and propensity score matching study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46;R&#46; Gonzalez Juanatey"
                            1 => "A&#46; Cordero"
                            2 => "J&#46;M&#46; Castellano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2021"
                        "volumen" => "42"
                        "numero" => "Suppl&#46; 1"
                      ]
                    ]
                  ]
                ]
              ]
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            37 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2021 ESC Guidelines on cardiovascular disease prevention in clinical practice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "F&#46;L&#46;J&#46; Visseren"
                            1 => "F&#46; Mach"
                            2 => "Y&#46;M&#46; Smulders"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehab484"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2021"
                        "volumen" => "42"
                        "paginaInicial" => "3227"
                        "paginaFinal" => "3337"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34458905"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Effects of aspirin for primary prevention in persons with diabetes mellitus"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2018"
                        "volumen" => "379"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global burden of 369 diseases and injuries in 204 countries and territories&#44; 1990&#8211;2019&#58; a systematic analysis for the Global Burden of Disease Study 2019"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "T&#46; Vos"
                            1 => "S&#46;S&#46; Lim"
                            2 => "C&#46; Abbafati"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(20)30925-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2020"
                        "volumen" => "396"
                        "paginaInicial" => "1204"
                        "paginaFinal" => "1222"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33069326"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0470"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Atherosclerosis&#58; the cost of illness in Portugal"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46; Costa"
                            1 => "J&#46; Alarc&#227;o"
                            2 => "A&#46; Amaral-Silva"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Revista Portuguesa de Cardiologia &#40;Engl Ed&#41;"
                        "fecha" => "2021"
                        "volumen" => "40"
                        "paginaInicial" => "1204"
                        "paginaFinal" => "1222"
                      ]
                    ]
                  ]
                ]
              ]
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            41 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiovascular disease prevention with a multidrug regimen in the developing world&#58; a cost-effectiveness analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T&#46;A&#46; Gaziano"
                            1 => "L&#46;H&#46; Opie"
                            2 => "M&#46;C&#46; Weinstein"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2006"
                        "volumen" => "368"
                        "paginaInicial" => "679"
                        "paginaFinal" => "686"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cost-benefit analysis of the polypill in the primary prevention of myocardial infarction and stroke"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "N&#46;J&#46; Wald"
                            1 => "J&#46;M&#46; Luteijn"
                            2 => "J&#46;K&#46; Morris"
                            3 => "D&#46; Taylor"
                            4 => "P&#46; Oppenheimer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10654-016-0122-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Epidemiol"
                        "fecha" => "2016"
                        "volumen" => "31"
                        "paginaInicial" => "415"
                        "paginaFinal" => "426"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26946426"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cost-effectiveness and public health benefit of secondary cardiovascular disease prevention from improved adherence using a polypill in the UK"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "V&#46; Becerra"
                            1 => "A&#46; Gracia"
                            2 => "K&#46; Desai"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmjopen-2014-007111"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMJ Open"
                        "fecha" => "2015"
                        "volumen" => "5"
                        "paginaInicial" => "e007111"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25991449"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cost-effectiveness of a fixed-dose combination pill for secondary prevention of cardiovascular disease in China&#44; India&#44; Mexico Nigeria&#44; and South Africa&#58; a modelling study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46;K&#46; Lin"
                            1 => "A&#46;E&#46; Moran"
                            2 => "K&#46; Bibbins-Domingo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2214-109X(19)30339-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Glob Health"
                        "fecha" => "2019"
                        "volumen" => "7"
                        "paginaInicial" => "e1346"
                        "paginaFinal" => "e1358"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31477544"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Modeling the cost effectiveness and budgetary impact of Polypills for secondary prevention of cardiovascular disease in the United States"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "T&#46;A&#46; Gaziano"
                            1 => "A&#46; Pandya"
                            2 => "S&#46; Sy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ahj.2019.04.020"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am Heart J"
                        "fecha" => "2019"
                        "volumen" => "214"
                        "paginaInicial" => "77"
                        "paginaFinal" => "87"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31174054"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cost-effectiveness analysis of use of a polypill versus usual care or best practice for primary prevention in people at high risk of cardiovascular disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "S&#46; Jowett"
                            1 => "P&#46; Barton"
                            2 => "A&#46; Roalfe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0182625"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS ONE"
                        "fecha" => "2017"
                        "volumen" => "12"
                        "paginaInicial" => "e0182625"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28873416"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cost-effectiveness of the CNIC-polypill strategy compared with separate monocomponents in secondary prevention of cardiovascular and cerebrovascular disease in Portugal&#58; the MERCURY study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "C&#46; Aguiar"
                            1 => "F&#46; Araujo"
                            2 => "G&#46; Rubio-Mercade"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.36469/001c.39768"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Health Econ Outcomes Res"
                        "fecha" => "2022"
                        "volumen" => "9"
                        "paginaInicial" => "134"
                        "paginaFinal" => "146"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36475278"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Registo Nacional de S&#237;ndromes Coron&#225;rias Agudas&#58; 15 anos de um registo prospetivo cont&#237;nuo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.repc.2017.07.016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Port Cardiol &#40;Engl Ed&#41;"
                        "fecha" => "2018"
                        "volumen" => "37"
                        "paginaInicial" => "563"
                        "paginaFinal" => "573"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30008312"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cost-Effectiveness of the CNIC-Polypill &#40;aspirin&#44; atorvastatin&#44; ramipril&#41; in post-ischemic stroke patients for the prevention of recurrent event based on improved control of cardiovascular risk factors"
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                            1 => "C&#46; Aguiar"
                            2 => "G&#46; Rubio"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur Stroke J"
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                        "volumen" => "6"
                        "numero" => "Suppl&#46;"
                        "paginaInicial" => "104"
                      ]
                    ]
                  ]
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            50 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reduction of cardiovascular events in patients with cardiovascular disease with the CV-polypill&#58; a retrospective and propensity score matching study"
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                          "etal" => true
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                            2 => "J&#46;M&#46; Castellano"
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                  "host" => array:1 [
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                      "Revista" => array:4 [
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                        "numero" => "Suppl&#46; 1"
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                ]
              ]
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              "identificador" => "bib0525"
              "etiqueta" => "52"
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                  "referenciaCompleta" => "Relat&#243;rio de avalia&#231;&#227;o do pedido de comparticipa&#231;&#227;o de medicamento para USO humano &#8211; DCI &#8211; &#193;cido acetilsalic&#237;lico &#43; Atorvastatina &#43; Ramipril &#91;Internet&#93;&#46; Available from&#58; <a target="_blank" href="https://www.infarmed.pt/documents/15786/1437513/Trinomia+%28DCI+%C3%81cido+acetilsalic%C3%ADlico+%2B+Atorvastatina+%2B+Ramipril%29/bc7d8a36-c451-477c-aad4-959134216845">https&#58;&#47;&#47;www&#46;infarmed&#46;pt&#47;documents&#47;15786&#47;1437513&#47;Trinomia&#43;&#37;28DCI&#43;&#37;C3&#37;81cido&#43;acetilsalic&#37;C3&#37;ADlico&#43;&#37;2B&#43;Atorvastatina&#43;&#37;2B&#43;Ramipril&#37;29&#47;bc7d8a36-c451-477c-aad4-959134216845</a> &#91;cited 28&#46;10&#46;21&#93;&#46;"
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            52 => array:3 [
              "identificador" => "bib0530"
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