Abstract

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).