Timing of Initiation and Efficacy of Dual Antiplatelet Therapy in Minor Stroke or High-Risk TIA

BACKGROUND: Dual antiplatelet therapy (DAPT) is recommended within 24 hours for patients with minor ischemic stroke or high-risk transient ischemic attack. However, the optimal timing for initiating DAPT remains unclear. METHODS: From a prospective multicenter cohort involving 20 stroke centers between January 2011 and April 2023, patients with minor noncardioembolic ischemic stroke (National Institutes of Health Stroke Scale score ≤5) or high-risk transient ischemic attack who presented within 7 days of symptom onset were included. We evaluated outcomes based on in-hospital initiation of DAPT versus monotherapy (aspirin or clopidogrel alone). The primary outcome was a composite of recurrent stroke, myocardial infarction, and death within 90 days. Patients were grouped by time from symptom onset to hospital arrival: 0 to 24 hours, 24 to 72 hours, and >72 hours. Time-to-treatment effects were analyzed using Cox proportional hazards models, with inverse probability of treatment weighting based on propensity scores. The adjusted models incorporated demographic factors, baseline clinical characteristics, vascular risk factors, stroke subtype, relevant arterial status, and prior antiplatelet use. RESULTS: Among the 41 530 patients (mean age, 66.3 years; 25 771 [62%] male), 25 112 (60.5%) received DAPT. The 90-day primary outcome occurred in 2663 (10.7%) of the DAPT group versus 1900 (11.6%) in the monotherapy group (hazard ratio, 0.82 [95% CI, 0.77-0.87]). The benefit of DAPT was most pronounced when 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 for initiation beyond 72 hours (hazard ratio, 1.25 [95% CI, 1.01-1.55]). Time-dependent analysis showed a benefit crossing the null at ≈42 hours. CONCLUSIONS: Early initiation of DAPT was associated with the greatest clinical benefit, consistent with current guideline recommendations. The therapeutic effect appeared to decline progressively beyond this period, with an estimated threshold around 42 hours.