Beta-blockers for hypertension

Background This review is an update of the Cochrane Review published in 2007, which assessed the role of beta-blockade as first-line therapy for hypertension. Objectives To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension. Search methods In December 2011 we searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and reference lists of previous reviews; for eligible studies published since the previous search we conducted in May 2006. Selection criteria Randomised controlled trials (RCTs) of at least one year duration, which assessed the effects of beta-blockers compared to placebo or other drugs, as first-line therapy for hypertension, on mortality and morbidity in adults. Data collection and analysis We selected studies and extracted data in duplicate. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and combined them using the fixed-effects or random-effects method, as appropriate. Main results We included 13 RCTs which compared beta-blockers to placebo (4 trials, N=23,613), diuretics (5 trials, N=18,241), calcium-channel blockers (CCBs: 4 trials, N=44,825), and renin-angiotensin system(RAS) inhibitors (3 trials, N=10,828). Three-quarters of the 40,245 participants on beta-blockers used atenolol. Most studies had a high risk of bias; resulting from various limitations in study design, conduct, and data analysis. Total mortality was not significantly different between beta-blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11; I-2=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95% CI 1.00 to 1.14; I-2=2%). Total cardiovascular disease (CVD) was lower for beta-blockers compared to placebo (RR 0.88, 95% CI 0.79 to 0.97; I-2=21%). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; I-2=0%), since there was no significant difference in coronary heart disease (CHD) between beta-blockers and placebo. There was no significant difference in withdrawals from assigned treatment due to adverse events between beta-blockers and placebo (RR 1.12, 95% CI 0.82 to 1.54; I-2=66%). The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95% CI 1.08-1.29; I-2=0%), but was not different from that of diuretics or RAS inhibitors. In addition, there was an increase in stroke in beta-blockers compared to CCBs (RR 1.24, 95% CI 1.11-1.40; I-2=0%) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; I-2=29%). However, CHD was not significantly different between beta-blockers and diuretics, CCBs or RAS inhibitors. Participants on beta-blockers were more likely to discontinue treatment due to adverse events than those on RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; I-2=12%), but there was no significant difference with diuretics or CCBs. Authors' conclusions Initiating treatment of hypertension with beta-blockers leads to modest reductions in cardiovascular disease and no significant effects on mortality. These effects of beta-blockers are inferior to those of other antihypertensive drugs. The GRADE quality of this evidence is low, implying that the true effect of beta-blockers may be substantially different from the estimate of effects found in this review. Further research should be of high quality and should explore whether there are differences between different sub-types of beta-blockers or whether beta-blockers have differential effects on younger and elderly patients.