Eur J Intern Med. 2026 Feb 19:106775. doi: 10.1016/j.ejim.2026.106775. Online ahead of print.
ABSTRACT
BACKGROUND: To systematically evaluate polypill effects on cardiovascular (CV) risk factors, CV outcomes, and adverse events in CV disease (CVD) prevention populations.
METHODS: Systematic searches were conducted in five databases from inception to November 7, 2025, for randomized controlled trials (RCTs) that assessed the effects of polypills for prevention of primary or secondary CVD. Three reviewers independently screened articles, extracted data, assessed risk of bias (RoB) and evaluated GRADE quality of evidence (QoE). Inverse variance meta-analyses were conducted. Primary outcomes included all-cause mortality (ACM), CV death, all-cause hospitalization (ACH), and CV hospitalization (CVH).
RESULTS: Thirteen RCTs (n = 27,836) were included. Seven RCTs investigated primary prevention, three secondary preventions, and three in both populations. When compared to controls, polypills had little to no effect on ACM (RR 0.93, 95 %CI 0.82-1.05, 9 RCTs), stroke (RR 0.61, 95 %CI 0.46-0.81, 4 RCTs), heart failure (RR 0.94, 95 %CI 0.57-1.53, 4 RCTs) and revascularization (RR 0.73, 95 %CI 0.49-1.10, 2 RCTs) and may slightly reduce CV death (RR 0.69, 95 %CI 0.57-0.83, 5 RCTs), CVH (RR 0.80, 95 %CI 0.60-1.06, 2 RCTs), and ACH (RR 0.89, 95 %CI 0.77-1.03, 3 RCTs). Polypills probably reduced MI slightly (RR 0.69, 95 %CI 0.50-0.95, 2 RCTs). Polypills had small, significant reductions of SBP, DBP, total cholesterol, and LDL, and small, non-significant increases of adverse events (AEs), serious AEs and adherence. Subgroup analyses were mostly consistent with main analyses.
CONCLUSIONS: In primary and secondary prevention settings, polypills had moderate reductions of CV outcomes, small effects on CV risk factors, and small increases of AEs.
PMID:41720660 | DOI:10.1016/j.ejim.2026.106775