Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation: A Systematic Review and Meta-analysis

Background: The use of anticoagulation in patients with atrial fibrillation is often limited by the significant risk of bleeding, and difficulties maintaining consistent adherence over time. These challenges have led to the development of left atrial appendage closure (LAAC) as an alternative stroke prevention strategy in this patient population. Our study aimed to evaluate LAAC versus medical therapy in patients with atrial fibrillation. Methods: A comprehensive search was conducted using PubMed, Embase, and Cochrane Library from database inception through April 1, 2026. The predefined endpoints were composite outcome of systemic embolism, cardiovascular mortality, or stroke in addition to other endpoints including all-cause mortality, cardiovascular mortality, strokes, and major bleeding. All outcomes were pooled using a random effect Mantel-Haenszel model. The between-study variance (τ2) was estimated using the Paul Mendel method, which is the preferred method when the number of included studies is small. Results: A total of five randomized controlled trials, 5,404 patients were analyzed; 2,878 underwent LAAC and 2,526 received medical therapy. The median follow-up across studies was 4 years. LAAC met noninferiority compared with medical therapy in atrial fibrillation for major bleeding (RR 0.86; 95% CI 0.59–1.26) and all-cause mortality (RR 0.93; 95% CI 0.71–1.22). In contrast, noninferiority was not met for the composite outcome (RR 0.97; 95% CI 0.64–1.47), cardiovascular mortality (RR 0.86; 95% CI 0.51–1.42), systemic embolism (RR 1.93; 95% CI 0.21–17.5), and all stroke (RR 1.11; 95% CI 0.73–1.67). Conclusion: This meta-analysis showed that LAAC was noninferior to anticoagulation for all-cause mortality and major bleeding, but it did not meet noninferiority for the other assessed outcomes, including stroke, cardiovascular mortality, and/or systemic embolism.