Comparative Efficacy and Safety of Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulants in Atrial Fibrillation: A Systematic Review and Meta-Analysis

Introduction: Left atrial appendage occlusion (LAAO) has emerged as an alternative to direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF), particularly in patients with contraindications to long-term anticoagulation. However, comparative efficacy and safety remain uncertain. Methods: We conducted a systematic review and meta-analysis of studies published up to September 2025. A total of 395 studies were screened, and 14 met eligibility criteria, encompassing 683,659 patients. Data on baseline demographics, thromboembolic outcomes, bleeding complications, and mortality were extracted. Pooled estimates were calculated using random-effects models in Stata 18.0. Risk of bias was assessed with ROBINS-I and RoB 2.0, and certainty of evidence was graded using GRADE. Results: Of the total population, 14,931 patients underwent LAAO and 640,888 received DOACs. The cohort included 287,031 males and 339,818 females, with hypertension present in 8262 LAAO and 189,627 DOAC patients, CKD in 4256 vs 122,521, and diabetes in 7422 vs 284,861, respectively. LAAO patients had a mean CHA₂DS₂-VASc score of 4.58 compared to 4.92 in DOAC patients. Meta-analysis showed no significant differences between LAAO and DOACs in all-cause mortality (RR 0.08; 95% CI -0.77 to 0.92), cardiovascular mortality (RR 0.67; 95% CI -0.60 to 1.94), thromboembolic events (RR 0.47; 95% CI -0.83 to 1.77), or major bleeding (RR 0.58; 95% CI -0.71 to 1.87). Conclusion: LAAO provides stroke prevention comparable to DOACs without significant differences in mortality or bleeding. LAAO may represent an appropriate option in AF patients with high bleeding risk or contraindications to anticoagulation. Further randomized trials are warranted to refine patient selection and confirm long-term outcomes.