Effects of Antihypertensive-drug Class on Interindividual Variation in Blood Pressure and Risk of Stroke: a Systematic Review and Meta-analysis

Introduction: 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.

Methods: 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.

Findings: 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.

Interpretation: 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.

Funding: None.