Key result
Fixed-dose combination therapy with at least three antihypertensive medications effectively lowers systolic blood pressure, with standard dose triple combinations reducing it by 10.6 to 41.4 mm Hg.
Why the study?
Fixed-dose combination therapy may overcome reasons for therapeutic inertia, but the available evidence on standard or low-dose combinations of at least three antihypertensive medicines needed synthesis.
Does fixed-dose combination therapy with at least three antihypertensive medications reduce blood pressure in adults?
Systematic Review (n=14,307)
Does fixed-dose combination therapy with at least three antihypertensive medications reduce blood pressure in adults?
Triple and quadruple combination antihypertensive polypills are effective and safe for lowering blood pressure, supporting their use as first-line therapy for stage 2 hypertension.
Supports polypill initiation in hypertension; extends RCT evidence on efficacy, adherence, and safety.
Fixed-dose combination (FDC) therapy may provide a solution to treatment gaps by overcoming reasons for therapeutic inertia. To synthesise and report on available evidence on standard or low-dose combination medicines that combine at least three antihypertensive medicines. A literature search was conducted via Scopus, Embase, PubMed and the Cochrane clinical trials database. Studies were eligible for inclusion if they were randomised clinical trials that included adults (>18 years) and examined the impact of at least three antihypertensive medications on blood pressure (BP). A total of 18 trials (n=14 307) were identified that examined combinations of three or four antihypertensive medicines. Ten trials investigated the effect of a standard dose triple combination polypill, four the effect of a low-dose triple and four the effect of a low-dose quadruple combination polypill. The mean difference (MD) in systolic BP ranged from -10.6 to -41.4 for the standard dose triple combination polypill in comparison with 2.1 to -34.5 for dual combination; -9.8 to -20.6 for a low-dose combination polypill in comparison with a MD of -0.9 to -5.2 for placebo; -9.0 to -29.3 for a low-dose combination polypill compared with -2.0 to -20.6 for monotherapy or usual care. All trials reported similar rates of adverse events. Ten studies reported medication adherence, six reported >95% adherence. Triple and quadruple combination antihypertensive medications are effective. Studies of low-dose triple and quadruple combinations involving treatment naïve populations suggest initiating such combinations are safe and effective as first-line therapy for stage 2 hypertension (BP >140/90 mm Hg).
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O’Hagan et al. (2023) conducted a systematic review in Hypertension (n=14,307). Fixed-dose combination therapy with at least three antihypertensive medications vs. Dual combination, monotherapy, usual care, or placebo was evaluated on Systolic blood pressure (MD -10.6 to -41.4 (standard triple vs dual); MD -9.8 to -20.6 (low-dose vs placebo)). Fixed-dose combination therapy with at least three antihypertensive medications effectively lowers systolic blood pressure, with standard dose triple combinations reducing it by 10.6 to 41.4 mm Hg.
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