Direct oral anticoagulant dose vs dual antiplatelet therapy after left atrial appendage closure in patients with nonvalvular atrial fibrillation: a systematic review and meta-analysis.

Left atrial appendage closure (LAAC) is increasingly used in patients with non-valvular atrial fibrillation (NVAF) who are at high risk of bleeding. However, the optimal post-procedural antithrombotic strategy remains uncertain. This meta-analysis compares the efficacy and safety of direct oral anticoagulants (DOACs) versus dual antiplatelet therapy (DAPT) following LAAC. A systematic review and meta-analysis were conducted according to PRISMA and Cochrane guidelines. PubMed, Embase, and Cochrane were searched from inception to November 2025 for randomized controlled trials and cohort studies comparing DOACs with DAPT after LAAC in NVAF patients. Outcomes included all-cause mortality, cardiac mortality, stroke, major bleeding, device-related thrombosis (DRT), and thromboembolic events. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effects models as appropriate. Seven studies (3 RCTs and 4 observational studies) comprising 2,103 patients (1,003 DOAC; 1,096 DAPT) were included. DOAC therapy significantly reduced all-cause mortality (RR = 0.55, 95% CI 0.34-0.89), major bleeding (RR = 0.55, 95% CI 0.37-0.81), and device-related thrombosis (RR = 0.46, 95% CI 0.24-0.91) compared with DAPT. No statistically significant differences were observed for stroke, cardiac mortality, or overall thromboembolic events, although effect estimates consistently favored DOACs. Thromboembolic events associated with major bleeding were markedly lower with DOACs (RR = 0.14, 95% CI 0.05-0.36). However, sensitivity analyses restricted to randomized controlled trials did not demonstrate statistically significant benefits for all-cause mortality, major bleeding, or device-related thrombosis. Therefore, the observed overall benefit appeared to be mainly driven by observational studies, and these findings should be interpreted cautiously. DOAC therapy after LAAC may be associated with a favorable clinical profile compared with DAPT, with significant reductions in all-cause mortality, major bleeding, and device-related thrombosis in the overall pooled analysis. However, these benefits were not confirmed in sensitivity analyses restricted to randomized controlled trials and appeared to be primarily driven by observational studies. Therefore, these findings should be interpreted cautiously and should not be used to support a definitive preference for DOACs over DAPT without further adequately powered randomized evidence.