Direct oral anticoagulants compared to aspirin for embolic stroke of undetermined source: A comprehensive meta-analysis

BACKGROUND: The use of anticoagulation for stroke prevention in embolic stroke of undetermined source (ESUS) is hypothesized to be beneficial over conventional antiplatelet use. However, randomized controlled trials (RCTs) have not found clear benefits, even when assessing cardioembolic enriching features. This study aimed to perform a meta-analysis exploring the efficacy and safety of direct oral anticoagulants (DOACs) following ESUS. METHODS: PubMed, Scopus, and Cochrane Central were systematically searched for studies comparing DOACs versus aspirin after ESUS. The primary outcome was stroke recurrence, and the safety outcome was major bleeding. A random-effects model was used for the analyses. Statistical analysis was performed using Review Manager Web 8.0.0 (RevMan Web). RESULTS: 14,582 patients were included from 9 studies, of which 4 were RCTs. 7,341 (50.3 %) received DOACs as secondary prevention. For stroke recurrence, there was noted non-statistically significant trends towards benefit for DOACs (OR 0.93; 95 % CI 0.81-1.06; p = 0.29; I² = 34 %). No differences were found for major bleeding (HR 1.57; 95 % CI 0.86-2.86; p = 0.15; I² = 63 %). Among the atrial cardiomyopathy subgroup, no benefit was observed (OR 0.88; 95 % CI 0.50-1.55; p = 0.67; I² = 39 %). CONCLUSION: There is insufficient evidence to recommend the use of DOACs over aspirin following ESUS for the prevention of stroke recurrence. Nevertheless, the fears of increased bleed risks were also not seen. Further efforts should be directed towards identifying potential embolic sources and the population that benefit from OAC.