Effects of polypills on cardiovascular outcomes: Meta-analysis of clinical trials and observational studies

Cardiovascular polypills, that combine aspirin, antihypertensive and statin, are controversial with respect to cardiovascular risk factors (CVRFs) and cardiovascular events (CVE). We conducted a meta-analysis to examine their effects.

A systematic review was conducted, searching clinical studies, both randomised and observational, that compared polypills versus administering the individual drugs separately. Four bibliographic databases (PubMed, Cochrane Library, Science Direct, and Google Scholar) were searched till December 2024. Risk of bias was assessed using the Newcastle-Ottawa Scale, the Cochrane bias risk assessment tool and the Egger's test. We developed separate analyses for the CNIC-polypill (ramipril, aspirin and atorvastatin), which is recommended by the WHO, and other polypills with different compositions. Outcomes CVRF (systolic and diastolic blood pressure or SBP and DBP, and LDL cholesterol), CVE, and adherence were meta-analysed, estimating mean differences (MD) and relative risks (RR) with 95% confidence intervals (CIs).

There were 15 studies (n=24,364) included. Randomised trials (n=13) and observational studies (n=2) both showed low risk of bias. The CNIC-polypill decreased SBP (MD=-1.43mmHg [95% CI: -2.86; -0.00], p=0.05), DBP (MD=-2.62mmHg [95% CI: -5.41; 0.18], p=0.07), LDL cholesterol (MD=-5.52mg/dL [95% CI: -8.66; -2.38], p=0.0006), and CVE (RR=0.82 [95% CI: 0.73-0.92], p=0.0007), in clinical trials and observational studies combined. The other polypills also decreases SBP (MD=-2.93mmHg [95% CI: -3.96; -1.91], p<0.000001), DBP (MD=-1.52mmHg [95% CI: -2.00; -1.05], p<0.00001), LDL (MD=-10.48mg/dL [95% CI: -16.89; -4.07], p=0.001), and CVE (RR=0.77 [95% CI: 0.68-0.87], p<0.0001). There was higher therapeutic adherence both with the CNIC-polypill (RR=1.16 [95% CI: 1.12-1.21], p<0.00001) as well as with other polypills (RR=1.26 [95% CI: 1.04-1.52], p=0.02).

Polypills were effective in reducing CVRF and CVE, and improved adherence compared to taking the constituent individual drugs separately.