Abstract Body (Do not enter title and authors here): Background: Embolic stroke of undetermined source (ESUS) represents approximately 20% of ischemic strokes. The optimal treatment strategy for secondary prevention remains uncertain for patients with ESUS. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the safety and efficacy of direct oral anticoagulants (DOACs) versus aspirin therapy in patients with a history of ESUS.
Methods: PubMed, Embase, Cochrane and Web of science databases were systematically searched for eligible trials until March 2024. The primary outcome of interest was recurrent stroke. Major bleeding and clinically relevant non-major bleeding (CRNMB) were assessed as safety outcomes. We pooled hazard rations (HRs) with 95% confidence intervals (CIs) for analysis.
Results: Four RCTs comparing direct oral anticoagulants (DOACs) versus aspirin were included comprising 13,970 patients, of whom 6,989 (50%) were randomized to the DOACs group. The mean follow-up was 16 months. Compared to aspirin, DOACs did not reduce the incidence of recurrent stroke (HR: 0.95; 95% CI: 0.81-1.09; p=0.44), ischemic stroke (HR: 0.91; 95% CI: 0.79-1.06; p=0.23), all-cause mortality (HR: 1.11; 95% CI: 0.87-1.42; p=0.40), and major bleeding (HR: 1.56; 95% CI: 0.85%-2.86; p=0.15). However, patients in the DOACs group presented significantly higher incidence of CRNMB (HR: 1.54; 95% CI: 1.23-1.92; p=0.0002) when compared with the aspirin group.
Conclusion: Compared with aspirin, DOACs use was associated with an elevated risk of CRNMB and did not demonstrate superior efficacy in preventing recurrent stroke among patients with ESUS.