Polypill with or without aspirin in persons without cardiovascular disease

• Main Authors: Bosch, J. (Author), Christou, C. (Author), Dagenais, G. (Author), Dans, A. (Author), Gamra, H. (Author), Gao, P. (Author), Girish, P. (Author), Joseph, P. (Author), Lopez-Jaramillo, P. (Author), McCready, T. (Author), Pais, P. (Author), Rocha, C. (Author), Santoso, A. (Author), Talukder, S. (Author), Teo, K. (Author), Tyrwhitt, J. (Author), Xavier, D. (Author), Xavier, F. (Author), Yeates, K. (Author), Yusoff, K. (Author), Yusuf, S. (Author)
• Format: Article
• Language: English
• Published: Massachussetts Medical Society 2021
• Series: New England Journal of Medicine
• Subjects: acetylsalicylic acid; adult; aged; Aged; Anticholesteremic Agents; antihypertensive agent; Antihypertensive Agents; antithrombocytic agent; Article; Aspirin; atenolol; Atenolol; blood; blood pressure; Blood Pressure; cardiovascular disease; Cardiovascular Diseases; cardiovascular mortality; cerebrovascular accident; Cholesterol, LDL; clinical outcome; clinical trial; combination drug therapy; controlled study; dizziness; double blind procedure; drug combination; Drug Combinations; drug effect; drug safety; Drug Therapy, Combination; drug withdrawal; dyspepsia; female; Female; follow up; gastritis; gastrointestinal hemorrhage; heart arrest; heart failure; heart infarction; heart muscle revascularization; human; Humans; hydrochlorothiazide; Hydrochlorothiazide; hypocholesterolemic agent; hypotension; incidence; Incidence; low density lipoprotein cholesterol; low density lipoprotein cholesterol level; low drug dose; male; Male; Medication Adherence; medication compliance; middle aged; Middle Aged; mortality; multicenter study; muscle disease; peptic ulcer; placebo; Platelet Aggregation Inhibitors; priority journal; ramipril; randomized controlled trial; risk factor; Risk Factors; simvastatin; Simvastatin; systolic blood pressure; vitamin D
• Online Access: View Fulltext in Publisher; View in Scopus
• ISBN: 00284793 (ISSN)
• DOI: 10.1056/NEJMoa2028220

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. © 2020 Massachusetts Medical Society.