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Meta-Analysis
. 2025 Jul;32(4):375-385.
doi: 10.1007/s40292-025-00720-1. Epub 2025 Jun 9.

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

Umar G Adamu  1 , Kabo Mojela  2 , El-Ameen U Adamu  3 , Dike Ojji  4 , Nqoba Tsabedze  2
Affiliations
Meta-Analysis

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

Umar G Adamu et al. High Blood Press Cardiovasc Prev. 2025 Jul.

Abstract

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.

Keywords: Blood pressure control; Hypertension; Low- and middle-income countries (LMICs); Low-dose triple single pill combination therapy; Meta-analysis; Randomized controlled trials (RCTs).

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Conflict of interest statement

Declarations. Conflict of interest: All authors certify that they have no affiliations with or involvement in any organizationor entity with any financial interest or non-financial interest in the subject matter or materialsdiscussed in this manuscript. Ethics Approval: The work described has not been published, it is not under consideration for publicationelsewhere, and its publication is approved by all authors and tacitly or explicitly by theresponsible authorities where the work was carried out; if accepted, it will not be publishedelsewhere in the same form, in English or in any other language, including electronically, withoutthe written consent of the copyright-holder. Consent to Publish: The authors of the present study give consent to publish this paper.

Figures

Fig. 1
Fig. 1
Preferred reporting items for systematic reviewa and meta analysis (PRISMA) flow diagram of study screening and selection
Fig. 2
Fig. 2
A Blood pressure control at six months. B Proportion of patients who achieved blood pressure control at 6 weeks. C Proportion of patients who achieved blood pressure control at 12 weeks. D Mean change in systolic blood pressure (mmHg). E Mean change in diastolic blood pressure (mmHg). CI, confidence interval; RR, risk ratio; SC, standard care; SD, standard deviation; SPC, single pill combination
Fig. 3
Fig. 3
A Adherence. B Withdrawal. C Total adverse events. D Serious adverse events. E Hypotension
Fig. 4
Fig. 4
A ROB 2 assessment of bias. B Funnel plot of publication bias
See this image and copyright information in PMC

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