A Cochrane review [Abstract] 1 included 13 studies with a total of 91 561 subjects (beta-blockers vs. placebo or no treatment 4 trials, n=23 613; vs. diuretics 5 trials, n=18 241; vs. calcium-channel blockers 4 trials, n=44 825 participants; vs. renin-angiotensin system inhibitors 3 trials, n=10 828). Most of the evidence comes from trials with atenolol as the beta-blocker used (75% of beta-blocker participants). No studies involving newer vasodilating beta-blockers (e.g. nebivolol) were found.
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; 4 studies, n=23 613), diuretics or renin-angiotensin system (RAS) inhibitors, but was higher for beta-blockers compared to calcium-channel blockers (CCBs; RR 1.07, 95% CI 1.00 to 1.14; 4 studies, n=44 825, NNTH=200 for 5 years). 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; 4 studies, n=23 613, NNTB=140 for 5 years). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; 4 studies, n=23 613, NNTB=200 for 5 years); 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; 2 studies, n=19 915, NNTH=80), but was not significantly 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 to 1.40; 3 studies, n=44 167, NNTH=180) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; 2 studies, n=9 951, NNTH=65). CHD was not significantly different between beta-blockers and diuretics or CCBs or RAS inhibitors. In the single study involving participants aged 65 years and older, atenolol was associated with an increased CHD incidence compared to diuretics (RR 1.63, 95% CI 1.15 to 2.32).
Patients on beta-blockers were more likely to discontinue treatment due to side effects than those on RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; 2 studies, n=9 951, NNTH=18), but there was no significant difference with placebo, diuretics or CCBs.
Comment: The quality of evidence is downgraded by study limitations (unclear allocation concealment).
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