TY - JOUR
T1 - Polypill with or without aspirin in persons without cardiovascular disease
AU - Yusuf, S.
AU - Joseph, P.
AU - Dans, A.
AU - Gao, P.
AU - Teo, K.
AU - Xavier, D.
AU - Lopez-Jaramillo, P.
AU - Yusoff, K.
AU - Santoso, A.
AU - Gamra, H.
AU - Talukder, S.
AU - Christou, C.
AU - Girish, P.
AU - Yeates, K.
AU - Xavier, F.
AU - Dagenais, G.
AU - Rocha, C.
AU - McCready, T.
AU - Tyrwhitt, J.
AU - Bosch, J.
AU - Pais, P.
N1 - Funding Information:
Supported by grants from the Wellcome Trust (089725/B/09/Z), the Canadian Institutes of Health Research (IPR-119993), and the Heart and Stroke Foundation of Canada (000448) and by the Population Health Research Institute and Hamilton Health Sciences Research Institute, St. John’s Research Institute, Cadila Pharmaceuticals, the Philippine Council for Health Research and Development, and Secretaria de Salud del Departamento de Santander, Colombia.
Funding Information:
Dr. Yusuf reports receiving lecture fees and travel support from AstraZeneca and grant support, lecture fees, and travel support from Bayer; Dr. D. Xavier, receiving grant support from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Coca-Cola India, and Pfizer and lecture fees from Eli Lilly and Sanofi; Dr. Dagenais, receiving lecture fees from Bayer; and Dr. Bosch, receiving advisory board fees and fees for adjudication from Bayer. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
© 2020 Massachusetts Medical Society.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/21
Y1 - 2021/1/21
N2 - BACKGROUND A polypill comprising statins, multiple blood-pressure-lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. METHODS Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed. RESULTS A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the doubleplacebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups. CONCLUSIONS Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk.
AB - BACKGROUND A polypill comprising statins, multiple blood-pressure-lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. METHODS Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed. RESULTS A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the doubleplacebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups. CONCLUSIONS Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk.
UR - http://www.scopus.com/inward/record.url?scp=85096582030&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2028220
DO - 10.1056/NEJMoa2028220
M3 - Article
C2 - 33186492
AN - SCOPUS:85096582030
VL - 384
SP - 216
EP - 228
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 3
ER -