Single versus dual antiplatelet therapy for stroke prevention in patients with first-ever embolic stroke of undetermined source

Background: This study aims to evaluate the efficacy and safety of dual antiplatelet therapy (DAPT) versus single antiplatelet therapy (SAPT) for patients with a first-ever embolic stroke of undetermined source (ESUS). Methods: We assembled a multicenter cohort and a propensity score-matched (PSM) subset to compare DAPT with SAPT. The primary outcome was a composite of recurrent ischemic stroke, myocardial infarction, or all-cause death, and the safety outcome was major bleeding. Follow-up extended to 3 years (median, 2.6 years). We used Cox proportional hazards models to complement time-stratified (piecewise) analyses and restricted mean survival time (RMST). Results: In the total cohort (n = 1675), DAPT was associated with a lower hazard of the composite outcome (adjusted hazard ratio (HR) = 0.56, 95% confidence interval (CI) = 0.44–0.70). Stroke recurrence and mortality were likewise reduced, while myocardial infarction events were infrequent. There was no significant difference in major bleeding between groups (e.g. incidence-rate ratio ≈1.0; p > 0.05). The annual incidence rate for the composite was 5.5%/year with DAPT versus 10.1%/year with SAPT. Time-stratified analyses revealed that the ischemic benefit was most pronounced between 6 and 12 months and appeared to persist thereafter. Bleeding, however, showed only a numerical increase beyond 1 year without statistical significance. RMST differences favored DAPT from 1 year onward and increased over 1000 days. Conclusion: In this ESUS cohort, DAPT was associated with fewer ischemic events and no increased major bleeding. The benefit was most evident at 6–12 months and was sustained over a longer follow-up period.