TY - JOUR
T1 - Efficacy and Safety of Quarter-Dose Blood Pressure-Lowering Agents
T2 - A Systematic Review and Meta-Analysis of Randomized Controlled Trials
AU - Bennett, Alexander
AU - Chow, Clara K.
AU - Chou, Michael
AU - Dehbi, Hakim-Moulay
AU - Webster, Ruth
AU - Salam, Abdul
AU - Patel, Anushka
AU - Neal, Bruce
AU - Peiris, David
AU - Thakkar, Jay
AU - Chalmers, John
AU - Nelson, Mark
AU - Reid, Christopher
AU - Hillis, Graham S.
AU - Woodward, Mark
AU - Hilmer, Sarah
AU - Usherwood, Tim
AU - Thom, Simon
AU - Rodgers, Anthony
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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.
KW - blood pressure
KW - hypertension
KW - meta-analysis
KW - pharmacology
KW - safety
UR - http://www.scopus.com/inward/record.url?scp=85020156851&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.117.09202
DO - 10.1161/HYPERTENSIONAHA.117.09202
M3 - Review Article
C2 - 28584013
AN - SCOPUS:85020156851
VL - 70
SP - 85
EP - 93
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 1
ER -