Efficacy and safety of triple versus dual combinations of antihypertensive drugs: A systematic review and meta-analysis of double-blind randomized clinical trials

Abstract We evaluated the blood pressure (BP)-lowering efficacy and safety of triple vs dual therapy of antihypertensive drug (AHTD) combinations, among adults with hypertension. Seventeen randomized, double-blind trials (41 comparisons and 13,461 participants) comparing triple versus dual therapy for ≥3 weeks identified by multiple literature databases searches including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) until October 2024 were included in the meta-analysis. Triple therapy achieved a greater reduction in systolic BP (SBP) compared with dual therapy (26.9 vs. 21.7 mmHg, mean difference 5.4 mmHg [95% CI, 4.7–6.2]). Among patients receiving dual therapy at submaximal and maximal doses, the addition of a third drug further reduced SBP by 7.5 and 3.6 mmHg, respectively. BP control was significantly better with triple therapy (60% vs. 47%, RR=1.34 [1.27–1.41]). Withdrawal due to adverse events was slightly higher in the triple therapy group (4% vs. 3%, RR=1.5 [1.2–1.8]). Triple AHTD therapy provides superior BP reduction and is well-tolerated compared to dual therapy.