Beyond the 24-hour window: Timing-dependent effectiveness of dual antiplatelet therapy in minor stroke and high-risk TIA

초록

Background and aims: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is recommended within 24 h for minor ischemic stroke or high-risk transient ischemic attack (TIA). However, its effectiveness beyond this window remains uncertain. We examined whether timing of patient arrival after symptom onset modifies the effectiveness of DAPT on clinical outcomes. Methods: We analyzed 41,530 patients with acute minor ischemic stroke (NIHSS ≤5) or high-risk TIA (onset ≤7 days) from a nationwide registry (CRCS-K-NIH, 2011–2023). Patients who received reperfusion therapy or non-standard antiplatelet regimens were excluded. In-hospital DAPT (aspirin plus clopidogrel) was compared with monotherapy. Patients were stratified by arrival time: ≤24 h, 24–72 h, and 72 h–7 days. The primary outcome was a composite of stroke recurrence, myocardial infarction, or all-cause mortality within 90 days. Inverse probability of treatment weighting (IPTW) using propensity scores was applied to adjust for baseline differences. Results: Crude event rates were 10.65 % with DAPT vs. 11.64 % with monotherapy. After IPTW adjustment, DAPT was associated with reduced risk (HR 0.82, 95 % CI 0.77–0.87). The benefit was significant for arrivals within 24 h (11.89 % vs. 14.53 %; HR 0.74, 95 % CI 0.69–0.79), but not for 24–72 h (9.49 % vs. 8.30 %; HR 1.00, 95 % CI 0.88–1.15) or 72 h–7 days (7.22 % vs. 5.56 %; HR 1.25, 95 % CI 1.01–1.55). When modeled continuously, the benefit of DAPT crossed the null at approximately 42 h. Conclusions: DAPT was beneficial in patients arriving within ~42 h of symptom onset. The effect was time-dependent, underscoring the need for early presentation.