Abstract 4142294: Anticoagulation for the Prevention of Stroke Recurrence in Embolic Stroke of Undetermined Source: a meta-analysis

Background: The 2021 AHA/ASA stroke guideline highlighted the importance of identifying clinical factors to discern patients with embolic stroke of undetermined source (ESUS) who may benefit from anticoagulation as a key area for future investigation. Research Question: Which subsets of patients with ESUS potentially benefit from anticoagulation for secondary prevention? Aims: To identify potential subsets of ESUS who may benefit from direct oral anticoagulants (DOAC). Methods: Electronic databases were searched from January 1 st , 2014 to May 10 th , 2024 to identify randomized controlled trials (RCTs) comparing DOACs and aspirin for secondary prevention after ESUS. The efficacy outcome was comparative ischemic stroke recurrence between DOACs and aspirin. The safety outcome was major bleeding.Random-effects meta-analysis using restricted maximum likelihood method was performed, with a prespecified subgroup analysis based on participants with evidence of patent foramen ovale (PFO) and with signs of, or risk factors for atrial cardiopathy. Results: We identified four RCTs including 13,970 participants. Overall, DOAC did not lead to a significant reduction in the unselected ESUS population (RR, 0.92; 95% CI, 0.80 to 1.05; I 2 = 0%; Figure A). In patients with signs of or risk factors for atrial cardiopathy, there was a significant 16% reduction in recurrent ischemic stroke with DOAC (RR, 0.84; 95% CI, 0.70 to 0.99; I 2 = 0%; Figure A). Notably, a significant 36% reduction in stroke recurrence was observed in the subgroup using criteria more specific to atrial pathology for signs of atrial cardiopathy (RR, 0.64; 95% CI, 0.43 to 0.97; I 2 = 25%; Figure A). Conversely, no difference was noted in the subgroup using cardiac biomarkers criteria for signs of atrial cardiopathy (RR, 1.05; 95% CI, 0.78 to 1.43; I 2 = 0%; Figure A). The risk of major bleeding outside ICH was significantly higher with DOACs than with aspirin (RR, 1.63; 95% CI, 1.08 to 2.47; I 2 = 0%; Figure B). Conclusions: The use of DOAC was associated with a significantly lower risk of ischemic stroke recurrence in patients with ESUS presenting with signs of or risk factors for atrial cardiopathy, especially in those meeting criteria more specific to atrial pathology.