Bleeding Complications in Anticoagulated Patients With Atrial Fibrillation and Sepsis: A Propensity‐Weighted Cohort Study

BACKGROUND Sepsis may adversely affect bleeding risk in anticoagulated patients with atrial fibrillation (AF), but the impact of warfarin treatment in such patients is poorly described. This registry-based nationwide cohort study examined safety of oral anticoagulant treatment (OAC) in patients with preexisting AF who were hospitalized because of incident sepsis in the period 2000-2015. METHODS AND RESULTS We identified 3030 AF patients who were warfarin users at the time of sepsis diagnosis, and we used inverse probability of treatment weighting to compare the rates of bleeding, thromboembolic events, and death within 90 days after sepsis diagnosis with a comparable cohort of 55721 patients without warfarin treatment and known AF. Weighted 90-day bleeding rates were slightly higher among warfarin users compared with nonusers (0.14 versus 0.12 per 100 person-years), yielding a weighted hazard ratio of 1.19 (95% confidence interval, 1.00-1.41). Thromboembolic event rates during the 90-days after sepsis were marginally higher among warfarin users versus nonusers (0.04 versus 0.03; hazard ratio: 1.25, 95% confidence interval, 0.89-1.76), while the 90-day all-cause mortality was substantially lower among warfarin users (hazard ratio: 0.64, 95% confidence interval, 0.58-0.69). Various sensitivity analyses conducted to challenge the robustness these findings yielded results that were consistent with the main findings. CONCLUSIONS AF patients who are on warfarin therapy at sepsis diagnosis experienced an increase in bleeding rates within the 3 months following sepsis. Warfarin use was associated with lower mortality, despite virtually comparable thromboembolic event rates.