Beta-blockers for hypertension. Cochrane Database of Systematic Reviews

Review

Beta-blockers for hypertension
CS Wiysonge, H Bradley, BM Mayosi, R Maroney, A Mbewu, LH Opie, J Volmink

Cochrane Database of Systematic Reviews 2007 Issue 2Copyright © 2007
The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.DOI: 10.1002/14651858.CD002003.pub2
This version first published online: 24 January 2007 in Issue 1, 2007
Date of Most Recent Substantive Amendment: 25 October 2006
This record should be cited as: Wiysonge CS, Bradley H, Mayosi BM, Maroney R, Mbewu A, Opie LH, Volmink J. Beta-blockers for hypertension.
Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD002003. DOI: 10.1002/14651858.CD002003.pub2.

Abstract

Background

Two recent systematic reviews found first-line beta-blockers to be less effective in reducing the incidence of stroke and the combined endpoint of stroke, myocardial infarction, and death compared to all other antihypertensive drugs taken together. However, beta-blockers might be better or worse than a specific class of drugs for a particular outcome measure so that comparing beta-blockers with all other classes taken together could be misleading. In addition, these systematic reviews did not assess the tolerability of beta-blockers relative to other antihypertensive medications. We thus undertook this review to re-assess the place of beta-blockade as first-line therapy for hypertension relative to each of the other major classes of antihypertensive drugs.

Objectives

To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension.

Search strategy

We searched eligible studies up to June 2006 in the Cochrane Controlled Trials Register, Medline, Embase, and reference lists of previous reviews, and by contacting hypertension experts.

Selection criteria

We selected randomised controlled trials which assessed the effectiveness of beta-blockers compared to placebo, no therapy or other drug classes, as monotherapy or first-line therapy for hypertension, on mortality and morbidity endpoints in men and non-pregnant women aged 18 years or older.

Data collection and analysis

At least two authors independently applied study selection criteria, assessed study quality, and extracted data; with differences resolved by consensus. We expressed study results as relative risks (RR) with 95% confidence intervals (CI) and conducted quantitative analyses with trial participants in groups to which they were randomly allocated, regardless of which or how much treatment they actually received. In the absence of significant heterogeneity between studies (p>0.1), we performed meta-analysis using a fixed effects method. Otherwise, we used the random effects method and investigated the cause of heterogeneity by stratified analysis. In addition, we used the Higgins statistic (I2) to quantify the amount of between-study variability in effect attributable to true heterogeneity rather than chance.

Main results

Thirteen randomised controlled trials (N=91,561 participants), which met our inclusion criteria, compared beta-blockers to placebo or no treatment (4 trials with 23,613 participants), diuretics (5 trials with 18,241 participants), calcium-channel blockers (CCBs: 4 trials with 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 trials with 10,828 participants). The risk of all-cause mortality was not different between first-line beta-blockers and placebo (RR 0.99, 95%CI 0.88 to 1.11, I2=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14, I2=2.2%; ARI=0.5%, NNH=200). The risk of total cardiovascular disease (CVD) was lower for first-line beta-blockers compared to placebo (RR 0.88, 95%CI 0.79 to 0.97, I2=21.4%, ARR=0.7%, NNT=140). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I2=0%; ARR=0.5%, NNT=200); coronary heart disease (CHD) risk was not significantly different between beta-blockers and placebo. The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95%CI 1.08 to 1.29, I2=0%; ARI=1.3%, NNH=80), but was not significantly different from that of diuretics or RAS inhibitors. Increased total CVD was due to an increase in stroke compared to CCBs (RR 1.24, 95%CI 1.11 to 1.40, I2=0%; ARI=0.6%, NNH=180).There was also an increase in stroke with beta-blockers as compared to RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53, I2=29.1%; ARI=1.5%, NNH=65). CHD was not significantly different between beta-blockers and diuretics or CCBs or RAS inhibitors. In addition, patients on beta-blockers were more likely to discontinue treatment due to side effects than those on diuretics (RR 1.86, 95%CI 1.39 to 2.50, I2=78.2%, ARI=6.4% NNH=16) and RAS inhibitors (RR 1.41, 95%CI 1.29 to 1.54, I2=12.1%; ARI=5.5%, NNH=18), but there was no significant difference with CCBs.

Authors' conclusions

The available evidence does not support the use of beta-blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak effect of beta-blockers to reduce stroke and the absence of an effect on coronary heart disease when compared to placebo or no treatment. More importantly, it is based on the trend towards worse outcomes in comparison with calcium-channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics. Most of the evidence for these conclusions comes from trials where atenolol was the beta-blocker used (75% of beta-blocker participants in this review). However, it is not known at present whether beta-blockers have differential effects on younger and elderly patients or whether there are differences between the different sub-types of beta-blockers.

Plain language summary

At the present time members of the class of drugs called beta-blockers are commonly used as first-line treatment for elevated blood pressure. We asked whether this class of drugs was as good as other classes in preventing death, stroke and heart attacks associated with elevated blood pressure. The available scientific literature was searched to find all the randomised controlled trial (RCT) evidence to assess this question. Thirteen RCTs were found and these trials suggested that first-line beta-blockers for elevated blood pressure were not as good at decreasing mortality and morbidity as other classes of drugs: thiazides, calcium channel blockers, and renin angiotensin system inhibitors.