Abstract
Background
Non-valvular atrial fibrillation (NVAF) elevates the risk of stroke owing to thrombus development, especially in the left atrial appendage (LAA). Left atrial appendage occlusion (LAAO) provides stroke prophylaxis for those unable to tolerate prolonged anticoagulant therapy. This meta-analysis evaluates the effectiveness and safety of direct oral anticoagulants (DOACs) in comparison to vitamin K antagonists (VKAs) following LAAO, concentrating on ischemic stroke, systemic embolism (SE), severe bleeding, and device-related thrombosis.Methods
A comprehensive literature search was conducted in Web of Science, Cochrane Library, Embase, and PubMed for studies published between 2017 and 2025. The inclusion criteria were trials involving patients undergoing LAAO who were treated with either DOAC or VKA regimens. The primary outcomes included transient ischemic attack (TIA), SE, ischemic stroke, and major hemorrhage. Any major adverse event was defined as a composite of major bleeding, stroke, SE, device-related thrombosis, and all-cause mortality, and analyzed as a secondary/exploratory outcome due to heterogeneity in component reporting across studies. Meta-analysis was performed using random-effects models for all pooled analyses, given the anticipated clinical and methodological heterogeneity across studies. Subgroup and sensitivity analyses were conducted to further assess the robustness of the findings.Results
Twenty-one studies were included. DOACs had a considerably reduced incidence of serious bleeding (OR = 0.88, 95% CI: 0.80-0.98) and any major adverse event (OR = 0.88, 95% CI: 0.82-0.95) than VKAs, but there was no discernible difference in stroke or SE rates (OR = 0.86, 95% CI: 0.69-1.05). Exploratory subgroup analyses suggested potential differences in certain groups (e.g., North America, longer follow-up), but these should be interpreted as exploratory. Secondary outcomes, including peri-device leaks and device-related thrombosis, did not differ significantly between groups.Conclusions
DOACs may provide comparable thromboembolic protection with a lower risk of major bleeding than VKAs after LAAO. However, most available evidence is derived from non-randomized studies and remains subject to residual confounding, selection bias, and moderate-to-low certainty of evidence. Therefore, the observed benefits of DOACs should be interpreted cautiously. Further large-scale prospective studies and randomized controlled trials are needed to confirm these findings and inform optimal post-LAAO anticoagulation strategies.