Efficacy and Safety of Low-Dose Triple Single Pill Combination Versus Standard Care in the Management of Hypertension in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis of Three Randomized Controlled Trials.

Introduction: Low Low-dose triple single pill combination therapy is recommended for hypertension treatment. However, the efficacy and safety of these combinations in low- and middle-income countries (LMICs) remain unclear.

Aim: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose triple single pill combination therapy in controlling blood pressure (BP) in LMICs.

Methods: We systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for randomised controlled trials (RCTs) comparing low-dose triple single pill combination therapy with standard care for hypertension management up to 29 January 2025. Mean differences (MD) were computed for continuous outcomes and risk ratio (RR) with 95% confidence intervals (CI) for binary outcomes.

Results: Three RCTs comprising 1758 patients, of whom 752 (43%) received low-dose triple single pill combination therapy, were included. The proportion of patients that achieved target BP at six weeks was higher with this therapy (RR 1.89; 95% CI 1.29, 2.75; P < 0.001). Compared with standard care, it significantly reduced SBP (MD - 5.30 mmHg; 95% CI - 9.55, - 0.92; P = 0.017), DBP (MD - 3.50 mmHg; 95% CI - 4.95, - 2.05; P < 0.001), and urine albumin-to-creatinine ratio (RR 0.59; 95% CI 0.44, 0.80; P < 0.001). No significant differences in adherence, withdrawal, or adverse effects were observed between groups.

Conclusion: In this meta-analysis, the use of a low-dose triple single pill combination in hypertensive patients in LMICs led to earlier and sustained blood pressure control and reduced urine albumin-to-creatinine ratio, with a safety profile comparable to standard care. PROSPERO registration: Number: CRD42025647884, Date: 15 February 2025.