Timing of Initiation and Efficacy of Dual Antiplatelet Therapy in Minor Stroke or High-Risk TIA
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Background
Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is recommended within 24 hours for patients with minor ischemic stroke or high-risk transient ischemic attack (TIA). However, the optimal timing for initiating DAPT in real-world practice remains unclear.
Methods
We conducted a secondary analysis of the Clinical Research Center for Stroke–Korea National Institute of Health (CRCS-K-NIH) registry, a prospective multicenter cohort involving 20 stroke centers across South Korea between January 2011 and April 2023. A total of 41,530 patients with minor non-cardioembolic ischemic stroke (NIHSS ≤5) or high-risk TIA 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. Time-to-treatment effects were analyzed using Cox proportional hazards models, with inverse probability of treatment weighting based on propensity scores.
Results
Among the 41,530 patients (mean age 66.3 years; 62% male), 60.5% received DAPT. The 90-day primary outcome occurred in 10.7% of the DAPT group versus 11.6% in the monotherapy group (HR 0.82; 95% CI, 0.77–0.87). The benefit of DAPT was most pronounced when initiated within 24 hours (HR 0.74; 95% CI, 0.69–0.79). No significant benefit was observed when DAPT was initiated between 24 and 72 hours (HR 1.00; 95% CI, 0.88–1.15), and a higher risk was suggested for initiation beyond 72 hours (HR 1.25; 95% CI, 1.01–1.55). Time-dependent analysis showed benefit crossing the null at ∼42 hours.
Conclusions
Early initiation of DAPT—particularly within 24 hours—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.
