The committee considered that all-cause mortality was the most essential of the critical outcomes for decision making and the discussion of the committee focussed on this outcome. In patients with HF-REF and atrial fibrillation, the meta-analysis showed a small increase in the number of deaths in the beta-blocker group, however, the committee were not confident in the evidence due to the wide confidence intervals around the absolute effect estimate, which ranged from a clinically important harm to a clinically important benefit of beta-blockers. Similarly, the data suggest a slight increase in the risk of stroke, but the committee was not confident in the effect estimate due to the very serious imprecision. Therefore, the committee was not confident that the evidence actually showed harm in those prescribed beta-blockers. The evidence did not show any clinically important reduction in the number of heart-failure hospitalisations in people taking beta-blockers. The committee also noted the indirectness of this outcome: the data does not take into account the broader unintended consequences of the intervention Chronic Heart Failure Treating Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 such as adverse events leading to hospitalisation (for example, bradycardia). The committee noted that the uncertainty in the evidence is likely to be due to the fact that the analysis was a retrospective sub-group analysis. Due to this uncertainty the committee did not consider that they could make a recommendation for the use of beta-blockers in those with heart failure with reduced ejection fraction and atrial fibrillation. Therefore, the committee agreed to make a research recommendation for a prospective RCT to be undertaken to determine whether or not beta-blockers should be given to patients with HF-REF and AF. 