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).
- delivery of healthcare
- pharmacology, clinical
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Contributors EO, DM, TN and CKC designed the review. DM developed the search strategy. EO and DM extracted data. EO analysed the data. EO and DM drafted the manuscript. TN and CKC revised the manuscript critically for important intellectual content. All authors read, contributed to and approved the final version of the manuscript. CKC is the guarantor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.
Author note This review was invited following a presentation by Professor Clara Chow at the World Heart Summit in Geneva, 2022.
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