Annals of Medicine and Surgery · Oct 13, 2026

Efficacy and safety of low-dose triple and quadruple combination pills for initial hypertension management: a systematic review and meta-analysis of RCTs

By Cheema AAA, Abbas SM, Nadeem L et al.

Background: Hypertension is a leading modifiable risk factor for cardiovascular disease, yet global blood pressure (BP) control remains suboptimal. A low-dose combination (LDC) polypill may simplify therapy and enhance BP reduction. We synthesized randomized evidence on the efficacy and safety of initial LDC triple and quadruple antihypertensive pills. Methods: PubMed, ClinicalTrials.gov, WHO ICTRP, and the Cochrane Library were searched from inception to 20 May 2026. Randomized controlled trials (RCTs) comparing LDC triple- or quadruple-pill regimens with active comparators (monotherapy or usual care) or placebo were included. Random-effects meta-analyses estimated odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). Results: Fourteen RCTs ( n = 4082) were included. Versus active comparators, LDC increased achievement of target BP at 4–12 weeks (OR: 1.90; 95% CI: 1.40–2.57) and 6–12 months (OR: 1.76; 95% CI: 1.39–2.24). LDC reduced systolic BP (−3.33 mmHg; 95% CI: −6.59 to −0.06) and diastolic BP (MD: −2.71 mmHg; 95% CI: −4.57 to −0.86) versus active comparators, and lowered systolic BP versus placebo (−10.93 mmHg; 95% CI: −18.06 to −3.80). Overall adverse events were similar between groups, but dizziness/syncope/presyncope was slightly more frequent with LDC (OR: 1.41; 95% CI: 1.02–1.95). Headache was less common versus placebo (OR: 0.27; 95% CI: 0.08–0.95). Lipids and creatinine were unchanged; sodium (MD: −0.72 mmol/L) and potassium (MD: −0.19 mmol/L) decreased modestly. Conclusion: Initial LDC triple and quadruple pills improve BP control and are generally well tolerated, although a modest increase in dizziness was observed.

doi.org/10.1097/ms9.0000000000005722 Open access Interventions