This development has been associated with a progressive decline in the reported mortality of patients with HFREF over the past 10 years or so. However, in 2014 a high-profile individual patient data meta-analysis was published, which examined the role of beta-blockers in a specific sub-population of HREF patients who also have atrial fibrillation (AF). This paper failed to demonstrate the same mortality benefit of beta-blockers as had previously been seen in the overall HFREF population. Therefore it became important to review the guidance for the use of beta-blockers in this sub-population of patients. 6.2.2.2 Review question: What is the clinical and cost effectiveness of beta-blockers in the management of chronic heart failure in people with heart failure with reduced ejection fraction (HFREF) and atrial fibrillation? For full details see review protocol in Appendix A. Table 32: PICO characteristics of review question Population People diagnosed with HFREF with concomitant atrial fibrillation. Intervention(s) Beta-blockers: bisoprolol (up to 10mg once daily) carvedilol (up to 50mg twice daily) nebivolol (licensed in stable mild to moderate heart failure in people over 70 years) (up to 10mg once daily) metoprolol CR/XL(up to 200 mg once daily) In addition to usual care in CHF. Comparison(s) Placebo In addition to usual care in CHF. Outcomes CRITICAL All-cause mortality Health-related quality of life Unplanned hospitalisation IMPORTANT Other adverse events (stroke, bradycardia, hypotension) Improvement of NYHA class Study design Systematic reviews of RCTs RCTs 6.2.2.3 Clinical evidence A search was conducted for randomised trials comparing the effectiveness of beta-blockers versus placebo in addition to usual care in people with chronic heart failure and atrial fibrillation. One study Chronic Heart Failure Beta-blockers in heart failure and concomitant atrial fibrillation NICE 2018. All rights reserved. Subject to Notice of rights. 