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

Alexander Bennett, Clara K. Chow, Michael Chou, Hakim Moulay Dehbi, Ruth Webster, Abdul Salam, Anushka Patel, Bruce Neal, David Peiris, Jay Thakkar, John Chalmers, Mark Nelson, Christopher Reid, Graham S. Hillis, Mark Woodward, Sarah Hilmer, Tim Usherwood, Simon Thom, Anthony Rodgers

Research output: Contribution to journalReview articlepeer-review

42 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)85-93
Number of pages9
Issue number1
Publication statusPublished - 1 Jul 2017


Dive into the research topics of 'Efficacy and Safety of Quarter-Dose Blood Pressure-Lowering Agents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials'. Together they form a unique fingerprint.

Cite this