Left Atrial Appendage Occlusion Versus Anticoagulation in Nonvalvular Atrial Fibrillation

Background: Randomized trials of percutaneous left atrial appendage occlusion (LAAO) in nonvalvular atrial fibrillation span warfarin- and direct oral anticoagulant-based comparator frameworks, distinct clinical settings, and heterogeneous endpoint constructs, limiting interpretation of prior pooled analyses. We therefore performed an era-structured systematic review and meta-analysis of contemporary randomized evidence. Methods: We systematically searched PubMed, Embase and the Cochrane Central Register of Controlled Trials for randomized controlled trials comparing percutaneous LAAO with anticoagulation-based medical therapy in adults with nonvalvular atrial fibrillation. The prespecified primary quantitative outcome was clinically relevant nonprocedural bleeding in contemporary trials. Time-to-event effects were summarized as hazard ratio (HR) with 95% confidence interval (CI) and pooled using random-effects meta-analysis when appropriate. Thromboembolic efficacy was summarized by trial-level synthesis because efficacy composites were not directly comparable across studies. Results: Six randomized trials involving 7,028 patients were included. The extended contemporary bleeding analysis comprised 3 trials and 5,002 randomized patients. Left atrial appendage occlusion was associated with significantly lower nonprocedural clinically relevant bleeding (pooled HR 0.51, 95% CI, 0.37-0.70; I 2 =0%; Figure 1). Across contemporary trials, thromboembolic efficacy appeared preserved relative to anticoagulation-based therapy, supported by trial-level noninferiority rather than a pooled superiority model. Warfarin-era trials provided historical proof of concept for efficacy preservation, whereas CLOSURE-AF, conducted in a very high-risk population with physician-directed best medical care, did not demonstrate noninferiority for its primary composite endpoint and was interpreted as contextual mixed-comparator evidence (Table 1). Conclusion: Across randomized evidence, the clearest contemporary advantage of percutaneous left atrial appendage occlusion is reduction in clinically relevant nonprocedural bleeding, whereas thromboembolic efficacy appears preserved at the trial level. These findings support left atrial appendage occlusion as a selective bleeding-sparing strategy in appropriately chosen patients rather than a universal replacement for anticoagulation.