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

Dhurjati, R.; Pant, R.; Satheesh, G.; Mittal, A.; Rodgers, A.; Salam, A.

2026-07-06 cardiovascular medicine
10.64898/2026.07.03.26356990 medRxiv
Show 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 to 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 to 1.41]). Withdrawal due to adverse events was slightly higher in the triple therapy group (4% vs. 3%, RR=1.5 [1.2 to 1.8]). Triple AHTD therapy provides superior BP reduction and is well-tolerated compared to dual therapy.

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