Direct Oral Anticoagulants vs Dual Antiplatelet Therapy After Left Atrial Appendage Occlusion

Background: Percutaneous left atrial appendage occlusion (LAAC) is increasingly used for stroke prevention in patients with nonvalvular atrial fibrillation, yet the optimal postprocedural antithrombotic regimen remains unclear. Purpose: To systematically evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared with dual antiplatelet therapy (DAPT) as postprocedural antithrombotic regimens following LAAC. Method: A systematic search was conducted across PubMed, Cochrane, Embase, and Clinicaltrials.gov through January 2026. A meta-analysis of randomized controlled trials (RCTs) comparing DOACs with DAPT after LAAC was performed, with Risk Ratio (RR) with 95% confidence intervals (CI) calculated and a trial sequential analysis to assess the conclusiveness of evidence. Heterogeneity was assessed using Higgins’ I 2 statistic. Statistical analyses were performed using R statistical software, version 4.4.2. Results: Three randomized trials including 704 patients (DOAC, n=368; DAPT, n=336) were analyzed. The median age of the participants was 77.3 years, with 34.5% being female. DOAC therapy significantly reduced device-related thrombosis compared with DAPT (0.5% vs 4.5%; RR 0.17, 95% CI 0.05-0.59; P < 0.01; I 2 = 0%) and was associated with a lower risk of the composite endpoint of mortality, stroke, bleeding, and device-related thrombosis (18.4% vs 30.0%; RR 0.62, 95% CI 0.43-0.89; P < 0.01; I 2 = 16%). Major bleeding occurred less frequently with DOACs (8.4% vs 12.2%; RR 0.61, 95% CI 0.39-0.95; P = 0.03; I 2 = 0%). There were no significant differences in stroke (RR 0.51, 95% CI 0.06-4.58; P = 0.45; I 2 = 0%), all-cause mortality (RR 0.60, 95% CI 0.24-1.53; P = 0.29; I 2 = 0%), or any bleeding (RR 0.63, 95% CI 0.38-1.03; P = 0.11; I 2 = 54%). Trial sequential analysis suggested benefit favoring DOACs but indicated that the required information size was not fully reached. Conclusion: Post-LAAC antithrombotic therapy with DOACs significantly reduces device-related thrombosis and major bleeding, offering a superior net clinical benefit compared with DAPT. While trial sequential analysis confirms these favorable safety and efficacy trends, the required information size has not been fully met, emphasizing the need for larger, definitive randomized trials.