| Samenvatting: | <p>Visit-to-visit variability in systolic blood pressure (SBP) predicts the subsequent risk of stroke, independent of mean SBP. It was reduced by amlodipine and increased by atenolol in the ASCOT-BPLA and MRC randomized controlled trials (RCTs), explaining the difference in risk of stroke between treatment groups that was not explained by mean SBP. Therefore, I performed a series of systematic reviews to examine the effects of all antihypertensive drugs in RCTs and how these effects relate to the risk of stroke.</p><p>Cochrane and Medline databases were searched for systematic reviews and RCTs of antihypertensive drugs. Baseline and follow-up data for mean (SD) SBP and DBP were extracted. Differences in inter-individual variance (SD2) in BP were expressed as a ratio (VR) and risk of stroke was compared by odds ratios (OR). Estimates were pooled by random-effects meta-analysis.</p><p>Compared to all other drugs, variability in SBP was reduced by randomization to calcium channel blockers (CCB: VR=0.81 95%CI 0.76-0.86, p<0.0001) and non-loop diuretics (0.87, 0.79-0.96, p=0.007), and increased by 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). Across all trials, effects of treatment on VR SBP (r²=0.372, p=0.0006) and on mean SBP (r²=0.328, p=0.0015) explained effects on stroke risk. Randomization to a CCB reduced the subsequent risk of stroke (OR=0.88, 0.83-0.94, p=0.0002). These effects on VR-SBP were dose-dependent and persisted when drugs were used in combination. Randomisation to a non-selective beta-blocker increased VR more than β1-selective agents (VR=1.23, 1.03-1.47, p=0.03), probably explaining the markedly increased risk of stroke in patients randomized to propranolol in the MRC-mild trial. Effects were not explained by changes in the incidence of new-onset atrial fibrillation.</p><p>Effects of antihypertensive drug classes on visit-to-visit variability in SBP explain effects of these drugs on the risk of stroke. CCBs are indicated for patients at increased risk of stroke due to episodic or variable systolic hypertension, but higher doses are required either as monotherapy or in combinations. Non-loop diuretics have smaller benefits, but beta-blockers are associated with increased variability in SBP and risk of stroke, particularly due to non-selective beta-blockers. These should be avoided in patients at an increased risk of stroke.</p>
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