@article{22864,
  author = {Woodward Mark and Salam A. and Thom Simon and Patel Anushka and Rodgers A and Chalmers J. and Webster Ruth and Chow Clara and Hillis Graham and Usherwood Tim and Thakkar Jay and Chou Michael and Dehbi Hakim-Moulay and Nelson Mark and Hilmer Sarah and Bennett Alexander and Reid Christopher and Peiris David and Neal Bruce},
  title = {Efficacy and Safety of Quarter-Dose Blood Pressure-Lowering Agents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.},
  abstract = {<p>
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&lt;0.001). Six comparisons were of dual quarter-dose therapy versus placebo, observing a -6.7/ -4.4 mm Hg (P&lt;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&lt;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&lt;0.001), +1.3/-0.3 (NS), and -13.1/-7.9 (P&lt;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.
</p>
},
  year = {2017},
  journal = {Hypertension},
  volume = {70},
  pages = {85-93},
  issn = {1524-4563},
  doi = {10.1161/HYPERTENSIONAHA.117.09202},
  language = {eng},
}