Abstract WP300: Anticoagulation versus antiplatelet for secondary prevention in embolic stroke of undetermined source: The Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence Study
Authors: Siegler James , Penckofer Mary , Badillo Goicoechea Elena , Eklund Kelsey , Stretz Christoph , Lineback Christina , Khasiyev Farid , Kerrigan Deborah , Ali Hamid , Aboul-Nour Hassan , de Havenon Adam , Culbertson Collin , Melkumova Emiliya , Jillella Dinesh , Dumitrascu Oana , Doolittle Charles , Yahnke Ian , Sathya Anvitha , Brown Samantha , Kang Jieun , Bowman Anna , Brorson James , Shahrivari Mahan , Elangovan Cheran , Sloane Kelly , Alvi Muhammad , Krishnaiah Balaji , Kam Wayneho , Farooqui Mudassir , Nahab Fadi , Rojas-Soto Diana , Sharma Richa , Thottempudi Neeharika , Nedelcu Simona , Smith Matthew , Herpich Franziska , Glover Patrick , Chahien Dalia , Sehgal Siddharth , Liebeskind David , Linares Guillermo , Daniel Jean-Philippe , Al Kasab Sami , Singh Eesha , D'Souza Marissa , Gaudio Elizabeth , Aziz Yasmin , Yaghi Shadi , Salehi Omran Setareh , Thon Jesse 
Published: January 2025

Introduction:
Four randomized clinical trials have not demonstrated the superiority of anticoagulation over antiplatelet therapy in the prevention of recurrent embolic stroke of undetermined source (ESUS). In this multicenter observational cohort study, we evaluated long-term outcomes associated with various antithrombotic strategies according to potential embolic sources.

Methods:
A multicenter retrospective observational cohort of consecutive adult patients with ESUS was queried (n=27 sites). Comparisons were made between patients treated with single or combination antiplatelet therapy versus anticoagulation (direct oral anticoagulant, vitamin K antagonist, low molecular weight heparin) with or without antiplatelet therapy initiated within 7 days of stroke. The primary composite outcome of recurrent stroke, major bleeding, or death was assessed using unadjusted and adjusted Cox proportional hazards regression, with clustering by site. Causal inference was assessed using inverse probability of treatment weighted regression adjustment (IPTWRA), accounting for propensity for antiplatelet treatment, with effect estimates summarized as the average treatment effect (ATE) over time (in days). Adjusted models accounted for age, stroke severity, vascular risk factors, and major categories of potential embolic sources.

Results:
Of the 2201 included patients (n=218 treated with anticoagulation) followed over a median of 564 days (interquartile range [IQR] 154-1124), the median age was 65y (IQR 54-74) and 49.8% were female. Patients treated with anticoagulation were older with more frequent previous stroke, concomitant left ventricular dysfunction, and more severe deficits. Over 4541 person-years of follow-up, the annualized incidence rate of the primary outcome was 14.6% (95% confidence interval [CI], 13.6%-15.8%). Compared to anticoagulation, antiplatelet(s) use was not associated with a lower risk of the primary outcome in the adjusted Cox model (HR 0.91, 95% CI, 0.64-1.29) or in the IPTWRA model (average treatment effect 0.14, 95% CI, -1376.6 to 1376.9). Major bleeding events trended toward significance in the adjusted Cox model (HR 0.51, 95% CI 0.25-1.04) but were no different with IPTWRA (ATE 58.9, 95% CI, -125.4 to 243.2).

Conclusions:
These results validate the observations of randomized trials indicating a lack of benefit of anticoagulation over antiplatelet therapy in ESUS. A more detailed analysis of heterogeneity of treatment effect is under way.