This systematic review and meta-analysis published in the European Journal of Internal Medicine included 13 randomized controlled trials (RCTs) comprising 27,836 participants to evaluate the effects of polypill therapy in cardiovascular disease (CVD) prevention. Seven trials examined primary prevention populations, three assessed secondary prevention, and three included both groups. Three reviewers independently screened studies, extracted data, assessed risk of bias, and evaluated the certainty of evidence using GRADE methodology. Inverse variance meta-analyses were conducted. Primary outcomes included all-cause mortality (ACM), cardiovascular (CV) death, all-cause hospitalization (ACH), and CV hospitalization (CVH).

Compared with controls, polypills showed little to no effect on stroke (RR 0.61; 95% CI 0.46–0.81), heart failure (RR 0.94; 95% CI 0.57–1.53), ACM (RR 0.93; 95% CI 0.82–1.05), or revascularization (RR 0.73; 95% CI 0.49–1.10). Polypills may slightly reduce CVH (RR 0.80; 95% CI 0.60–1.06), CV death (RR 0.69; 95% CI 0.57–0.83), and ACH (RR 0.89; 95% CI 0.77–1.03). Myocardial infarction was probably slightly reduced (RR 0.69; 95% CI 0.50–0.95).

Polypill therapy resulted in small but statistically significant reductions in systolic and diastolic blood pressure, LDL cholesterol, and total cholesterol. Small, non-significant increases in adverse events, serious adverse events, and adherence were observed. Subgroup analyses were largely consistent with primary findings.

In primary and secondary prevention settings, polypills had moderate reductions in cardiovascular outcomes, small effects on cardiovascular risk factors, and small increases in adverse events.