Bleeding Outcomes After Left Atrial Appendage Closure Compared With Long-Term Warfarin: A Pooled, Patient-Level Analysis of the WATCHMAN Randomized Trial Experience.

ABSTRACT

OBJECTIVES: The purpose of this study was to compare the relative risk of major bleeding with left atrial appendage (LAA) closure compared with long-term warfarin therapy. BACKGROUND: LAA closure is an alternative approach to chronic oral anticoagulation for the prevention of thromboembolism in patients with atrial fibrillation (AF). METHODS: We conducted a pooled, patient-level analysis of the 2 randomized clinical trials that compared WATCHMAN (Boston Scientific, Natick, Massachusetts) LAA closure with long-term warfarin therapy in AF. RESULTS: A total of 1,114 patients were included, with a median follow-up of 3.1 years. The overall rate of major bleeding from randomization to the end of follow-up was similar between treatment groups (3.5 events vs. 3.6 events per 100 patient-years; rate ratio [RR] 0.96; 95% confidence interval [CI] 0.66 to 1.40; p = 0.84). LAA closure significantly reduced bleeding >7 days post-randomization (1.8 events vs. 3.6 events per 100 patient-years; RR 0.49; 95% CI 0.32 to 0.75; p = 0.001), with the difference emerging 6 months after randomization (1.0 events vs. 3.5 events per 100 patient-years; RR 0.28; 95% CI 0.16 to 0.49; p < 0.001), when patients assigned to LAA closure were able to discontinue adjunctive oral anticoagulation and antiplatelet therapy. The reduction in bleeding with LAA closure was directionally consistent across all patient subgroups. CONCLUSIONS: There was no difference in the overall rate of major bleeding in patients assigned to LAA closure compared with extended warfarin therapy over 3 years of follow-up. However, LAA closure significantly reduced bleeding beyond the procedural period, particularly once adjunctive pharmacotherapy was discontinued. The favorable effect of LAA closure on long-term bleeding should be considered when selecting a stroke prevention strategy for patients with nonvalvular AF. (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy [PREVAIL]; NCT01182441).