Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulants in Atrial Fibrillation

Background: Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia in adults, affecting an estimated 3-6 million people in the United States, with projections rising to nearly 16 million cases by 2050. AF is associated with substantial morbidity and mortality, particularly due to an increased risk of ischemic stroke. Oral anticoagulation therapy, especially with direct oral anticoagulants (DOAC), remains the standard strategy for stroke prevention. However, DOAC therapy may be unsuitable for some patients because of an elevated risk of major bleeding, contraindications, or poor treatment adherence. Consequently, left atrial appendage closure (LAAC) has emerged as a nonpharmacologic alternative for stroke prevention in patients with AF who are at high bleeding risk or unable to tolerate long-term anticoagulation. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted through May 2026 to identify studies comparing LAAC versus DOAC in patients with AF. Meta-analysis inclusion criteria were established according to Cochrane Collaboration guidelines. Three independent reviewers performed data extraction and study quality assessment. Risk of bias was evaluated using the ROBINS-I and ROB-2 tools for observational studies and randomized controlled trials, respectively. Dichotomous outcomes were pooled using odds ratios (OR) with 95% CI through the inverse-variance method under a random-effects model. Time-to-event outcomes were analyzed using hazard ratios (HR) with corresponding 95% CI using a random-effects model. Statistical analyses were performed using RevMan version 5.3. Results: A total of 23 studies (8 RCT and 15 observational studies) were included examining 324,321 patients with AF (305,949 DOAC vs 18,372 LAAC). Compared with DOAC, LAAC showed no significant difference in the primary composite endpoint (stroke, systemic embolism, major bleeding, and cardiovascular death) (HR 0.86, 95% CI 0.72-1.03). Similarly, stroke risk was comparable between groups (OR 0.96, 95% CI 0.84-1.09). However, LAAC was associated with a significantly lower risk of major bleeding (HR 0.69, 95% CI 0.55-0.87). A trend toward reduced cardiovascular mortality (HR 0.75, 95% CI 0.56-1.00) and all-cause mortality (OR 0.76, 95% CI 0.56-1.02) was also observed with LAAC, although these findings did not consistently reach statistical significance. Conclusion: In patients with AF, LAAC showed comparable efficacy to DOAC for stroke prevention, with a significantly lower risk of major bleeding and a potential reduction in mortality. Further large-scale randomized trials are needed to better define the long-term comparative effectiveness of these strategies.