Recent evidence shows that polypills reduce major adverse cardiovascular events (MACE) compared with standard care, though many studies mix primary and secondary prevention populations, limiting clarity on subgroup effects. The impact of polypills on individual MACE components also remains unclear. This study assessed the effectiveness of polypills in preventing MACE and its components-cardiovascular mortality, coronary artery event (CAE), stroke, and heart failure-across primary, secondary, and mixed populations. Secondary outcomes included predefined MACE, all-cause mortality, coronary intervention, and peripheral vascular disease. We systematically searched PubMed, Scopus, and Web of Science for randomized controlled trials and cohort studies comparing polypills with usual care, monocomponent therapy, or placebo. Polypills were defined as fixed combinations of at least 2 of the following: aspirin, an antihypertensive agent, and a statin. Eighteen studies (15 randomized controlled trials, 3 cohorts; N = 32,425) were included. No significant reduction in MACE was observed in primary or mixed prevention groups, but polypills significantly reduced MACE in secondary prevention (risk ratio RR: 0.80, 95% confidence interval CI: 0.70-0.92). Predefined MACE was also reduced (RR: 0.79, 95% CI: 0.68-0.91), particularly in primary and secondary prevention. Cardiovascular mortality (RR: 0.69, 95% CI: 0.55-0.87) and CAE (RR: 0.77, 95% CI: 0.62-0.96) were significantly reduced, especially in secondary prevention. No significant effects were observed for stroke, heart failure, peripheral vascular disease, or all-cause mortality. Overall, polypills effectively reduce MACE in secondary prevention, mainly through reductions in cardiovascular mortality and CAE. Further work is needed to refine risk stratification and optimize polypill use in primary prevention.
Mirhosseini et al. (2026) studied this question.