Recurrent Stroke Following Left Atrial Appendage Closure in Patients with Breakthrough Stroke: A Systematic Review and Meta-Analysis

Objective: To determine the incidence of recurrent ischemic stroke following percutaneous left atrial appendage closure in patients with previous thromboembolic events despite oral anticoagulation. Methods: We conducted a systematic review and meta-analysis of studies of any design reporting ischemic stroke recurrence after left atrial appendage closure in patients with prior ischemic stroke despite oral anticoagulation therapy. The literature search was conducted in MEDLINE, Embase, and the Cochrane Library for studies published between 1 January 2010 and 31 December 2025. Data on study design, population characteristics, indexed intervention, and outcomes were extracted from each included report. The primary outcome was ischemic stroke occurring after left atrial appendage closure, as defined by each individual study. A pooled incidence rate was estimated using a random-effects model to account for anticipated between-study heterogeneity. The study is registered in Open Science Framework. The Risk of Bias in Non-randomized Studies of Interventions assessment tool was used to assess the risk of bias. Results: Overall, eight studies of a total of 1091 patients met the eligibility criteria. Patients were elderly (mean age range 71.8 to 78.1 years), 33% to 53% were women, and thromboembolic risk was consistently high (mean CHA2DS2-VASc scores ≥ 5.0). The risk of bias across the included studies was either moderate or serious. Antithrombotic therapy after left atrial appendage closure varied considerably across the included studies. In one study, all patients were discharged on dual antiplatelet therapy, whereas in five studies >70% received oral anticoagulation alone or in combination with antiplatelet therapy at discharge. In six studies, antithrombotic therapy at follow-up was reported, with the proportion of patients on oral anticoagulation alone or in combination with antiplatelet therapy at follow-up ranging from 8.1% to 100% in individual studies. Follow-up duration ranged from 1.0 to 3.1 years. At a mean follow-up of 17.7 months the pooled incidence of the ischemic stroke recurrence rate following left atrial appendage closure was 3.1% per year (95% confidence interval 2.35–4.20%). Conclusions: Among elderly patients with prior ischemic stroke despite oral anticoagulation, the recurrence rate of ischemic stroke following left atrial appendage closure was 3.1% per year. Given the residual risk of stroke recurrence and the substantial heterogeneity in post-procedural antithrombotic management observed across studies, prospective randomized trials are urgently needed to define both the protective impact of left atrial appendage closure and the optimal antithrombotic strategy in this high-risk population.