Efficacy and Safety of Dual Antiplatelet Therapy in Acute Ischemic Stroke With Recurrent Symptoms Post-thrombolysis: A Retrospective Cohort Study From the TriNetX US Collaborative Network

Introduction Recurrent neurological symptoms following thrombolysis in acute ischemic stroke (AIS) pose treatment challenges due to limited evidence guiding antiplatelet therapy. Current practices vary across institutions, reflecting a lack of standardized recommendations. This study uses the TriNetX US Collaborative Network to compare the safety and efficacy of dual antiplatelet therapy (DAPT) versus aspirin monotherapy (AM) in this patient population. Materials and methods This retrospective study analyzed de-identified electronic health records from the TriNetX US Collaborative Network, comprising over 66 hospitals. Adult patients aged ≥18 years with AIS who underwent thrombolysis within 4.5 hours of symptom onset between January 2015 and December 2023 were identified. Patients who developed recurrent neurological symptoms between one and 30 days post-thrombolysis and were subsequently treated with either aspirin alone or DAPT (aspirin plus clopidogrel) were included. The following two treatment groups were compared: AM and DAPT. Propensity score matching was performed to balance baseline characteristics between groups. The primary efficacy endpoint was recurrent ischemic stroke between 30 and 90 days, and primary safety endpoints were symptomatic intracranial hemorrhage (SICH) and 90-day all-cause mortality. Outcomes were evaluated using odds ratios and adjusted odds ratios, with statistical significance set at two-sided p<0.05. Results In this study, 2,502 patients met the inclusion criteria. After propensity-score matching, 889 patients were included in each treatment group. The incidence of recurrent ischemic stroke was similar between both groups (12.2% in the AM group and 12.6% in the DAPT group). The SICH rate was identical in both cohorts (1.1%). The DAPT cohort had a minor reduction in 90-day mortality compared to the AM cohort (1.6% vs 2.5%), although it was non-significant. Conclusion In AIS patients who develop recurrent symptoms after thrombolysis, DAPT did not demonstrate a significant advantage compared to AM in reducing recurrent stroke, SICH, or 90-day mortality. These findings support no observed benefit of routine DAPT escalation in this clinical context and support the need for prospective studies to guide management.