Left Atrial Appendage Closure Versus Oral Anticoagulation for Stroke Prevention in Non-Valvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Left atrial appendage closure (LAAC) has emerged as a non-pharmacological alternative to oral anticoagulation for stroke prevention in atrial fibrillation (AF). While early randomized trials established non-inferiority of LAAC versus warfarin, the comparative effectiveness of LAAC against contemporary direct oral anticoagulants (DOACs) remains less well characterized. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing percutaneous LAAC with oral anticoagulation-either warfarin or DOACs-in adults with non-valvular AF. PubMed/MEDLINE, Embase, and CENTRAL were searched from inception through May 2026. The primary outcome was a composite of stroke, systemic embolism (SE), and cardiovascular death. The key secondary outcome was major bleeding. Five RCTs comprising 6,116 patients were included. Pooled analysis demonstrated no significant difference between LAAC and oral anticoagulation for the composite primary outcome (RR 0.90; 95% CI 0.71-1.14; I²=34%). LAAC was associated with a statistically significant 24% reduction in major bleeding events compared with anticoagulation (RR 0.76; 95% CI 0.61-0.94; I²=0%). Individual secondary outcomes, including cardiovascular death, stroke, and SE, were not significantly different between groups. Subgroup analysis by anticoagulant class suggested a larger composite efficacy benefit of LAAC over warfarin (RR 0.69) than over DOACs (RR 0.98), consistent with the established intracranial hemorrhage reduction conferred by DOACs relative to warfarin. In conclusion, LAAC achieves comparable thromboembolic protection to oral anticoagulation while significantly reducing major bleeding, supporting its role as a viable alternative in appropriately selected patients with AF, particularly those at elevated bleeding risk.