AbstractBackground:Atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) have been independently associated with increased mortality; however, there is no evidence regarding beta-blocker cardioselectivity and long-term outcomes in patients with AF and concurrent COPD.Methods:This post hoc analysis of the MISOAC-AF randomized trial (NCT02941978) included patients hospitalized with comorbid AF. At discharge, all patients were classified according to the presence of COPD; patients with COPD on beta-blockers were classified according to beta-blocker cardioselectivity. Adjusted hazard ratios (aHRs) were calculated by using multivariable Cox regression models. The primary outcome was all-cause mortality, and the secondary outcomes were cardiovascular mortality and hospitalizations.Results:Of 1103 patients with AF, 145 (13%) had comorbid COPD. Comorbid COPD was associated with an increased risk of all-cause (aHR, 1.33; 95% confidence interval (CI), 1.02 to 1.73) and cardiovascular mortality (aHR 1.47; 95% CI, 1.10 to 1.99), but not with increased risk of hospitalizations (aHR 1.10; 95% CI, 0.82 to 1.48). The use of cardioselective versus non-cardioselective beta-blockers was associated with similar all-cause mortality (aHR 1.10; 95% CI, 0.63 to 1.94), cardiovascular mortality (aHR 1.33; 95% CI, 0.71 to 2.51), and hospitalizations (aHR 1.65; 95% CI 0.80 to 3.38).Conclusions:In recently hospitalized patients with AF, the presence of COPD was independently associated with increased risk of all-cause and cardiovascular mortality. No difference between cardioselective and non-cardioselective beta-blockers, regarding clinical outcomes, was identified.