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Efficacy and Safety of Quarter-Dose Blood Pressure-Lowering Agents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials


Bennett, A and Chow, CK and Chou, M and Dehbi, HM and Webster, R and Salam, A and Patel, A and Neal, B and Peiris, D and Thakkar, J and Chalmers, J and Nelson, M and Reid, C and Hillis, GS and Woodward, M and Hilmer, S and Usherwood, T and Thom, S and Rodgers, A, Efficacy and Safety of Quarter-Dose Blood Pressure-Lowering Agents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, Hypertension, 70, (1) pp. 85-93. ISSN 0194-911X (2017) [Refereed Article]

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DOI: doi:10.1161/HYPERTENSIONAHA.117.09202


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.

Item Details

Item Type:Refereed Article
Keywords:blood pressure, hypertension, meta-analysis, pharmacology, safety
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Cardiology (incl. Cardiovascular Diseases)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cardiovascular System and Diseases
Author:Nelson, M (Professor Mark Nelson)
ID Code:118478
Year Published:2017
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-07-12
Last Modified:2017-07-12

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