Impact of Heart Rate on Central Hemodynamics and Stroke: A Meta-Analysis of β-Blocker Trials

BACKGROUND In a meta-analysis, we investigated effects of beta-blockers on central hemodynamic measurements and explored the impact of heart rate (HR) on central hemodynamics and the risk of stroke. METHODS We searched randomized controlled trials that compared beta-blockers with other classes of antihypertensive drugs in reducing central systolic blood pressure (cSBP) and augmentation index (cAI) and in preventing stroke. A random-effects model was used to compute pooled estimates. RESULTS In 9 trials (n = 754), beta-blockers were less efficacious in reducing cAI than all the other classes of drugs (8.6%, P < 0.001). beta-blockers were also less efficacious in reducing cSBP than angiotensin converting enzyme inhibitors (7.7 mm Hg, P = 0.02) and angiotensin receptor blockers (3.6 mm Hg, P = 0.005) but not the other classes of drugs (P >= 0.50). In a meta-regression analysis of these 9 trials, the baseline-adjusted difference in HR between randomized groups was associated with cAI (7.0% increase for each 10 bpm decrease in HR, P = 0.02), which was associated with cSBP (1.2 mm Hg increase for each 1% increase in cAI, P = 0.009). In 5 outcome trials, the pooled OR of stroke was 1.23 (P < 0.001), which would be accounted for by the difference in cSBP derived from the above meta-regression analysis. CONCLUSIONS Slowing HR with beta-blockers may increase cAI and in turn may decrease cSBP less than with other classes of drugs. This mechanism might account for a smaller reduction in the risk of stroke when using beta-blockers to treat hypertension.