by Simone Salemme
For our May paper of the month, we have chosen Shin J, Lee K-J, Kim C, at al; CRCS-K-NIH Investigators. Timing of Initiation and Efficacy of Dual Antiplatelet Therapy in Minor Stroke or High-Risk TIA. Stroke. 2026 Jan 2; doi: 10.1161/STROKEAHA.125.053343
Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel is recommended early after minor ischaemic stroke or high-risk transient ischaemic attack (TIA), typically within 24 hours, yet real-world delays remain common. This prospective, multicentre cohort study used the CRCS-K-NIH registry to examine how the effectiveness of DAPT varies with time from symptom onset to hospital arrival and to estimate when the benefit of DAPT attenuates.
The authors analysed consecutive adults admitted to 20 stroke centres in South Korea between January 2011 and April 2023 with minor noncardioembolic ischaemic stroke (NIHSS ≤5) or high-risk TIA who presented within seven days of symptom onset and received aspirin or clopidogrel on admission. Patients with high-risk cardioembolic sources, acute reperfusion therapies, or antiplatelet/anticoagulant regimens other than aspirin or clopidogrel were excluded. Outcomes were compared between in-hospital initiation of DAPT versus monotherapy (aspirin or clopidogrel alone). The primary outcome was a 90-day composite of recurrent stroke, myocardial infarction, and death. Analyses were stratified by 0–24 hours, 24–72 hours, and >72 hours from symptom onset to hospital arrival and used Cox models with extensive adjustment, including inverse probability of treatment weighting based on propensity scores.
Among 41,530 patients (mean age 66.3 years; 62% male), 60.5% received DAPT. In the overall cohort, DAPT was associated with a lower risk of the primary outcome compared with monotherapy (hazard ratio 0.82; 95% CI 0.77–0.87). However, the association was strongly time-dependent. The benefit was most pronounced when DAPT was initiated within 24 hours (hazard ratio 0.74; 95% CI 0.69–0.79). No significant benefit was observed when DAPT was initiated between 24 and 72 hours (hazard ratio 1.00; 95% CI 0.88–1.15), and a higher risk was suggested when initiated beyond 72 hours (hazard ratio 1.25; 95% CI 1.01–1.55). Modelling time as a continuous variable indicated that the estimated treatment effect crossed the null at approximately 42 hours for the primary outcome (bootstrap 95% CI 33 to 55.5 hours), supporting the concept of a finite therapeutic window.
Overall, this large real-world analysis reinforces the urgency of early DAPT initiation after minor stroke or high-risk TIA and suggests that benefit may diminish progressively beyond the first day, with an estimated threshold around 42 hours. The authors note limitations inherent to observational designs (including potential residual confounding), non-systematic capture of major bleeding, and non-standardised dosing/loading protocols, as well as generalisability considerations outside the South Korean setting.
