RESUMO
BACKGROUND: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction. METHODS: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. RESULTS: A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P = 0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P = 0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups. CONCLUSIONS: Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).
Assuntos
Inibidores da Enzima Conversora de Angiotensina , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Inibidores da Agregação Plaquetária , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Atorvastatina/efeitos adversos , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , AVC Isquêmico/prevenção & controle , Infarto do Miocárdio/complicações , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/terapia , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Ramipril/efeitos adversos , Ramipril/uso terapêutico , Prevenção Secundária/métodosRESUMO
Despite the significant reduction in mortality, ischemic stroke is the leading cause of morbidity and mortality in adults in industrialized countries. Antiplatelet therapy has reduced the risk of stroke and other vascular events. Although most commonly used treatment is aspirin, other antiplatelet drugs with different mechanisms of action have been developed. Clopidogrel blocks platelet aggregation by inhibiting the adenosine diphosphate receptor and the subsequent activation of the complex IIb/IIIa. In addition to its antiplatelet action, it also has pleiotropic effects, reducing the inflammatory mechanisms that occur during ischemia. Clopidogrel has demonstrated a benefit over aspirin in preventing vascular events, especially in patients at high cardiovascular risk. In this paper we review the main studies that have been conducted with clopidogrel in preventing ischemic stroke, either as monotherapy or in combination with other antiplatelet agents.