“Efficacy and safety of low-dose combination (Quad pill and Triple pill) therapy versus standard of care and placebo in controlling hypertension: an updated systematic review and meta-analysis of randomized trials”

Hypertension is a leading cause of cardiovascular morbidity and mortality, yet the management remains suboptimal especially with monotherapy. Recently, low-dose triple and quadruple (quadpill) combinations have emerged as a promising therapeutic advancement resulting in control of hypertension. However, there still remains controversy around the long-term safety and efficacy of these therapies. We conducted an updated meta-analysis on the influence of these combinations on hypertension control. A systematic review and meta-analysis was conducted according to 2020 PRISMA guidelines and the protocol was prospectively registered in the PROSPERO. An extensive search on several databases including PubMed, Google scholar, C, and Cochrane Central Register of Trials. Primary outcome assessed was reduction in systolic blood pressure, and proportion of participants in range and secondary outcomes included: reduction in diastolic blood pressure, along with various safety outcomes. Low-dose combination significantly reduced systolic BP as compared to the placebo at 4–12 weeks (MD −14.97 mmHg), along with sustained reduction at 6 months (MD −6.58 mmHg). Patients who received low-dose combinations were more likely to reach target BP < 140/90, compared with a placebo drug (RR 2.18) and standard therapy (RR 1.37). Dizziness, headaches and pedal edema were noted more frequently in the intervention group, while MSK complaints were higher in the control populations. Our study’s findings suggest that low-dose combinations with triple and quadruple therapies are significantly more efficacious in reducing systolic and diastolic BPs of adult populations. However, generally higher adverse events were noted for the intervention group receiving low-dose combination therapy. © The Author(s), under exclusive licence to Springer Nature Limited 2026.