Nine RCTs (14,594 participants) were included.
When counting all people in all studies, 16% taking beta-blockers and 18% taking placebo stopped taking treatment before the end of the study. Beta-blockers were associated with a statistically significant reduction in all-cause withdrawal from study medication: the RR was 0.89 (95% CI: 0.81, 0.98) and the annual absolute risk reduction for withdrawal was 14 per 1,000 people (95% CI: -2, 29).
Beta-blocker therapy was associated with a significant reduction in all-cause mortality: the RR was 0.73 (95% CI: 0.62, 0.85) and the NNT for one year to prevent one death was 29.
Reductions in withdrawals and mortality occurred regardless of whether there was a run-in period before randomisation (P=0.74 and P=0.44, respectively, for withdrawal and mortality).
Beta-blocker therapy was associated with a significant reduction in hospitalisations for heart failure (8 studies; RR 0.72, 95% CI: 0.66, 0.83). The NNT to prevent one hospitalisation for heart failure was 25.
Beta-blockers were associated with a significant reduction in worsening of heart failure (4 studies; RR 0.83, 95% CI: 0.71, 0.98), and of withdrawal of therapy because of worsening heart failure (5 studies; RR 0.72, 95% CI: 0.54, 0.96).
Beta-blockers were associated with an increase in hypotension (7 studies; RR 1.41, 95% CI: 0.96, 2.06), and a significant increase in dizziness (4 studies; RR 1.37, 95% CI: 1.09, 1.71) and in bradycardia (7 studies; RR 3.62, 95% CI: 2.48, 5.28).
There was no clear association reported between beta-blockers and fatigue (3 studies; RR 1.04, 95% CI: 0.97, 1.11).
The risk of adverse effects associated with beta-blocker therapy did not differ significantly between those studies that did or did not have a pre-randomisation run-in treatment period, or in the study that included people with severe heart failure compared with the other studies.