Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in Atrial Fibrillation

Background: Direct oral anticoagulants (DOACs) remain first-line therapy for stroke prevention in nonvalvular atrial fibrillation (AF), but left atrial appendage closure (LAAC) is increasingly used in patients with high bleeding risk or intolerance to chronic anticoagulation. Contemporary randomized data comparing LAAC with DOAC-based therapy remain evolving and require consolidated synthesis. Research Question: We evaluated the efficacy and safety of LAAC versus DOAC-based therapy in randomized trials of patients with high-risk nonvalvular AF. Methods: This PROSPERO-registered meta-analysis (CRD420261384938) included randomized controlled trials comparing LAAC with DOAC-based therapy in patients with high-risk nonvalvular AF. Risk ratios (RRs) were pooled using inverse-variance methods, with fixed- or random-effects models applied according to between-study heterogeneity assessed by the I 2 statistic. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was assessed using GRADE. Results: Five randomized controlled trials were included, comprising 6,239 patients randomized to LAAC (n=3,126) or DOAC-based therapy (n=3,113). LAAC did not significantly differ from DOAC-based therapy for composite efficacy outcomes, all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, stroke, ischemic stroke, hemorrhagic stroke, or major bleeding. LAAC was associated with lower minor bleeding (RR 0.48, 95% CI 0.40-0.58; p<0.001; I 2 =6.9%) and clinically relevant nonprocedural bleeding (RR 0.56, 95% CI 0.48-0.65; p<0.001; I 2 =0.0%). However, systemic thromboembolism was higher with LAAC (RR 2.53, 95% CI 1.04-6.19; p=0.041; I 2 =28.9%), as were pericardial effusion (RR 2.35, 95% CI 1.15-4.83; p=0.019; I 2 =0.0%) and serious adverse events (RR 1.08, 95% CI 1.02-1.14; p=0.006; I 2 =0.0%). Conclusions: In contemporary randomized evidence, LAAC demonstrated broadly comparable major efficacy outcomes to DOAC-based therapy and was associated with lower nonprocedural bleeding, but with higher systemic thromboembolism, pericardial effusion, and serious adverse events. These findings support LAAC as a phenotype-selected alternative rather than a universal substitute for anticoagulation in high-risk nonvalvular AF.