Comparison of Bleeding Risks and All-Cause Death Between Warfarin and Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Chronic Obstructive Pulmonary Disease: A Multicenter Retrospective Cohort Study

Background: Chronic obstructive pulmonary disease (COPD) may influence bleeding in atrial fibrillation (AF). We evaluated bleeding and all-cause death risks under warfarin versus direct oral anticoagulants (DOACs). Methods: Based on a retrospective cohort from 12 centers of patients with AF on oral anticoagulation, we evaluated the associations of COPD and anticoagulant class with clinical outcomes using overlap-weighted logistic regression. Prespecified sensitivity and subgroup analyses were performed. Results: COPD was associated with higher bleeding risk only among patients treated with warfarin (total bleeding: odds ratio [OR] 2.53, 95% confidence interval [CI] 1.00–6.45; risk difference [RD] 9.05%, 95% CI 0.15%–22.50%; minor bleeding: OR 3.00, 95% CI 1.09–8.24; RD 8.53%, 95% CI 0.56%–21.53%). Among patients with AF and COPD, DOACs were associated with reduced risks of total bleeding (OR 0.08, 95% CI 0.01–0.50; RD –8.4%, 95% CI -22.0% to -5.3%) and minor bleeding (OR 0.01; RD -9.5%, 95% CI -23.1% to -4.5%) compared with warfarin. Subgroup analyses suggested that DOACs were associated with increased mortality at estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m² (OR 3.07, 95% CI 0.78–12.03; RD 9.9%) but lower mortality at eGFR <60mL/min/1.73m² (OR 0.20, 95% CI 0.05–0.78; RD -24.1%). Factor Xa inhibitors were associated with a higher major bleeding risk compared with dabigatran (OR 4.56, 95% CI 1.70–12.26; RD 10.2%, 95% CI 0.2%–20.1%; with a number needed to harm of 10). Conclusion: In AF with comorbid COPD, DOACs minimize bleeding versus warfarin and may confer survival benefit in renal impairment. Differential bleeding risk should be considered when choosing among DOACs.