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Efficacy and Safety of Quarter-Dose Blood Pressure–Lowering AgentsNovelty and Significance

Bennett, A; Chow, CK; Chou, M; Dehbi, H-M; Webster, R; Salam, A; Patel, A; ... Rodgers, A; + view all (2017) Efficacy and Safety of Quarter-Dose Blood Pressure–Lowering AgentsNovelty and Significance. Hypertension , 70 (1) pp. 85-93. 10.1161/HYPERTENSIONAHA.117.09202. Green open access

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Abstract

There is a critical need for blood pressure–lowering strategies that have greater efficacy and minimal side effects. Low-dose combinations hold promise in this regard, but there are few data on very-low-dose therapy. We, therefore, conducted a systematic review and meta-analysis of randomized controlled trials with at least one quarter-dose and one placebo and standard-dose monotherapy arm. A search was conducted of Medline, Embase, Cochrane Registry, Food and Drug Administration, and European Medicinal Agency websites. Data on blood pressure and adverse events were pooled using a fixed-effect model, and bias was assessed using Cochrane risk of bias. The review included 42 trials involving 20 284 participants. Thirty-six comparisons evaluated quarter-dose with placebo and indicated a blood pressure reduction of −4.7/−2.4 mm Hg (P<0.001). Six comparisons were of dual quarter-dose therapy versus placebo, observing a −6.7/ −4.4 mm Hg (P<0.001) blood pressure reduction. There were no trials of triple quarter-dose combination versus placebo, but one quadruple quarter-dose study observed a blood pressure reduction of −22.4/−13.1 mm Hg versus placebo (P<0.001). Compared with standard-dose monotherapy, the blood pressure differences achieved by single (37 comparisons), dual (7 comparisons), and quadruple (1 trial) quarter-dose combinations were +3.7/+2.6 (P<0.001), +1.3/−0.3 (NS), and −13.1/−7.9 (P<0.001) mm Hg, respectively. In terms of adverse events, single and dual quarter-dose therapy was not significantly different from placebo and had significantly fewer adverse events compared with standard-dose monotherapy. Quarter-dose combinations could provide improvements in efficacy and tolerability of blood pressure–lowering therapy.

Type: Article
Title: Efficacy and Safety of Quarter-Dose Blood Pressure–Lowering AgentsNovelty and Significance
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/HYPERTENSIONAHA.117.09202
Publisher version: https://doi.org/10.1161/HYPERTENSIONAHA.117.09202
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: blood pressure, pharmacology, hypertension, safety, meta-analysis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > Comprehensive CTU at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10060798
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