Beta-blockers in hypertension: overview and meta-analysis of randomized outcome trials

Background: Meta-analyses from randomized outcome-based trials have challenged the role of beta-blockers for the treatment of hypertension. However, because they often include trials on diseases other than hypertension, the role of these drugs in the choice of the blood pressure (BP)-lowering treatment strategies remains unclear. Methods: Electronic databases were searched for randomized trials that compared beta-blockers vs. placebo/no-treatment/less-intense treatment (BP-lowering trials) or beta-blockers vs. other antihypertensive agents in patients with or without hypertension (comparison trials). Among BP-lowering trials and according to baseline comorbidity, we separately considered trials in hypertension, trials without chronic heart failure or acute myocardial infarction, and trials with either chronic heart failure or acute myocardial infarction. Seven fatal and nonfatal outcomes were calculated (random-effects model) for BP-lowering or comparison trials. Results: A total of 84 BP-lowering or comparison trials (165 850 patients) were eligible. In 67 BP-lowering trials (68 478 patients; mean follow-up 2.5 years; baseline SBP/DBP, 136/82 mmHg), beta blockers were associated with a lower incidence of major cardiovascular events [risk ratio 0.85 and 95% confidence interval (95% CI) 0.78–0.92] and all-cause death (risk ratio 0.81 and 95% CI 0.75–0.86). Restriction of the analysis to five trials recruiting exclusively hypertensive patients (18 724 patients; mean follow-up 5.1 years; baseline SBP/DBP 163/94 mmHg), a -10.5/-7.0 mmHg BP decrease was accompanied by reduction of major cardiovascular events by 22% (95% CI, 6–34). In 24 comparison trials (103 764 patients, 3.92 years of mean follow-up), beta-blockers compared with other agents were less protective for stroke and all-cause death in all trials and in trials conducted exclusively in hypertensive patients (averaged risk ratio increase 20 and 6%, respectively, for both cases). Conclusion: Compared with other antihypertensive agents, beta-blockers appear to be substantially less protective against stroke and overall mortality. However, they exhibit a substantial risk-reducing ability for all events when prescribed to lower BP in patients with modest or more clear BP elevations, and therefore can be used as additional agents in hypertensive patients.