The review included 1,372 trials, of which 398 provided mean and SD data for systolic blood pressure (SBP) at follow-up. The results of the quality assessment were not reported. There was no evidence of reporting bias.
Variation in blood pressure: There were statistically significant reductions in variation of SBP resulting from the use of calcium-channel blockers (VR 0.81, 95% CI 0.76 to 0.86; 94 trials) and non-loop diuretic drugs (VR 0.87, 95% CI 0.79 to 0.96; 69 trials). Increased variation was reported following treatment with angiotensin-converting enzyme inhibitors (VR 1.08, 95% CI 1.02 to 1.15; 125 trials), angiotensin-receptor blockers (VR 1.16, 95% CI 1.07 to 1.25; 47 trials), and β-blockers (VR 1.17, 95% CI 1.07 to 1.28; 78 trials). Placebo comparison showed that calcium-channel blockers provided the greatest reduction in variation (VR 0.76, 95% CI 0.67 to 0.85; 34 trials).
Risk of events: Lower SD of SBP (VR ≤80) was associated with a significantly reduced risk of stroke (OR 0.79, 95% CI 0.71 to 0.87; 21 trials), despite only small reductions in mean SBP. There were no significant associations between VR and percentage difference in coefficient of variation for risk of myocardial infarction, heart failure, or cardiovascular mortality. Calcium-channel blockers showed a significantly reduced risk of stroke compared with all other drugs (OR 0.88, 95% CI 0.83 to 0.94; 19 trials). β-blockers showed an increased risk compared with all other drugs (OR 1.19, 95% CI 1.01 to 1.42; 10 trials).
Subgroup analyses: There was significant heterogeneity between trials in terms of VR (p<0.0001). Drug class contributed to a large proportion of the variation. Subgroup analysis showed similar results for crossover and parallel-group trials, and there was no significant difference in VR of SBP when the largest trial was removed from the analysis. Effects of VR on diastolic blood pressure showed a similar effect to those for the SD of SBP. Group variation was lower in trials of higher doses of calcium-channel blockers.