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Lancet. 2010 Mar 13;375(9718):906-15. doi: 10.1016/S0140-6736(10)60235-8.

Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis.

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Stroke Prevention Research Unit, University Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK.



Unexplained differences between classes of antihypertensive drugs in their effectiveness in preventing stroke might be due to class effects on intraindividual variability in blood pressure. We did a systematic review to assess any such effects in randomised controlled trials.


Baseline and follow-up data for mean (SD) of systolic blood pressure (SBP) were extracted from trial reports. Effect of treatment on interindividual variance (SD2) in blood pressure (a surrogate for within-individual variability), expressed as the ratio of the variances (VR), was related to effects on clinical outcomes. Pooled estimates were derived by use of random-effects meta-analysis.


Mean (SD) SBP at follow-up was reported in 389 (28%) of 1372 eligible trials. There was substantial heterogeneity between trials in VR (p<1 x 10(-40)), 68% of which was attributable to allocated drug class. Compared with other drugs, interindividual variation in SBP was reduced by calcium-channel blockers (VR 0.81, 95% CI 0.76-0.86, p<0.0001) and non-loop diuretic drugs (0.87, 0.79-0.96, p=0.007), and increased by angiotensin-converting enzyme (ACE) inhibitors (1.08, 1.02-1.15, p=0.008), angiotensin-receptor blockers (1.16, 1.07-1.25, p=0.0002), and beta blockers (1.17, 1.07-1.28, p=0.0007). Compared with placebo only, interindividual variation in SBP was reduced the most by calcium-channel blockers (0.76, 0.67-0.85, p<0.0001). Effects were consistent in parallel group and crossover design trials, and in analyses of dose-response. Across all trials, effects of treatment on VR of SBP (r2=0.372, p=0.0006) and on mean SBP (r2=0.328, p=0.0015) accounted for effects on stroke risk (eg, odds ratio 0.79, 0.71-0.87, p<0.0001, for VR< or =0.80), and both remained significant in a combined model.


Drug-class effects on interindividual variation in blood pressure can account for differences in effects of antihypertensive drugs on risk of stroke independently of effects on mean SBP.



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