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Beneficial effects of beta-blockade remain unclear in heart failure patients who have atrial fibrillation (AF), especially in the elderly. We evaluated the effect of nebivolol on cardiovascular outcomes in elderly patients with heart failure and AF.The SENIORS trial showed an overall benefit of nebivolol compared with placebo in 2128 heart failure patients >70 years of age. At baseline, AF was present in 738 (34.7%) patients. The primary outcome was all-cause mortality or cardiovascular hospitalizations. After 21 months, the cumulative incidence of the primary outcome was significantly more common in patients with AF compared with those with sinus rhythm (38.5% vs. 30.4%, respectively, P < 0.001). In patients with AF, nebivolol had no beneficial effect on the primary outcome [nebivolol vs. placebo, 37.1% vs. 39.8%, hazard ratio (HR) 0.92, 95% confidence interval (CI), 0.73–1.17, P = 0.46], in contrast to patients with sinus rhythm (28.1% vs. 32.9%, in the nebivolol vs. placebo group, respectively, HR 0.82, 95% CI 0.67–0.99, P = 0.049). In patients with AF, the primary outcome was similar in the impaired and preserved left ventricular ejection fraction (LVEF) groups (39.0% with LVEF ≤35% vs. 37.3% in patients with LVEF > 35%). There was also no evidence of benefit of nebivolol in AF patients stratified by LVEF.Nebivolol failed to improve outcomes in elderly patients with stable heart failure and co-existing AF, irrespective of LVEF. Furthermore, in patients with AF, outcome was comparable between patients with preserved and impaired LVEF.