02676nas a2200337   4500000000100000008004100001100001800042700001300060700001500073700001800088700001400106700001600120700001700136700001500153700001800168700001800186700001600204700001700220700002300237700001600260700001700276700002200293700002100315700001700336700001500353245014300368300001000511490000700521520179600528022001402324       2017                            d1 aWoodward Mark1 aSalam A.1 aThom Simon1 aPatel Anushka1 aRodgers A1 aChalmers J.1 aWebster Ruth1 aChow Clara1 aHillis Graham1 aUsherwood Tim1 aThakkar Jay1 aChou Michael1 aDehbi Hakim-Moulay1 aNelson Mark1 aHilmer Sarah1 aBennett Alexander1 aReid Christopher1 aPeiris David1 aNeal Bruce00aEfficacy and Safety of Quarter-Dose Blood Pressure-Lowering Agents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.  a85-930 v703 a<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.
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