Exploring the efficacy and safety of dual antiplatelet therapy in patients with embolic stroke of undetermined source according to stroke risk stratification: Propensity-score matched analysis

Introduction: Dual antiplatelet therapy (DAPT) is widely used for embolic stroke of undetermined source (ESUS) despite limited evidence regarding its efficacy and safety. This study compared DAPT and single antiplatelet therapy (SAPT) in patients with ESUS during hospitalization (first 7 days) and up to 30 days post-stroke, identifying subgroups that benefit most from DAPT. Methods: We retrospectively analyzed data from 4,505 patients with ESUS enrolled in a multicenter registry from 2014 to 2019. The primary outcome was early neurological deterioration (END) within 7 days of stroke onset, and the secondary outcome was major adverse cardiovascular events (MACE) within 30 days. Propensity score matching (1:1) was applied to balance baseline characteristics, and subgroup analysis was conducted based on Essen stroke risk score (ESRS, ≥3 vs. <3). Results: After matching, 1,835 patients were included in each treatment group for END analysis. In the overall cohort, DAPT did not significantly reduce END compared to SAPT (2.8 % vs. 3.5 %, adjusted OR 0.800; p = 0.202). Similarly, there was no significant difference in 30-day MACE (1.3 % vs. 1.4 %, adjusted HR 1.124; p = 0.512). However, in patients with ESRS ≥3, DAPT was associated with a statistically significant reduction in the risk of END (2.2 % vs. 5.4 %, PS-adjusted OR 0.563; p = 0.036), with no increase in major bleeding. Conclusion: DAPT did not confer benefit in unselected patients with ESUS but was effective in reducing END in high-risk individuals with ESRS ≥3. These findings support a risk-stratified approach to DAPT use in ESUS.