Heterogeneity in Time–Outcome Associations After Endovascular Thrombectomy: A Binational Registry Study

Background Although "time is brain" remains a core principle in acute stroke care, the association between treatment timing and functional outcomes after endovascular thrombectomy (EVT) varies across patients. Some individuals treated in extended time windows still achieve favorable outcomes, a phenomenon termed the "late window paradox." Differences in stroke pathophysiology across etiologies may contribute to heterogeneity in the time–outcome relationship after EVT. We investigated factors associated with heterogeneity in time-dependent EVT responsiveness, with particular attention to stroke etiology. Methods We analyzed data from two multicenter registries in Korea (CRCS-K) and Taiwan (TREAT-AIS) from January 2019 to April 2023. Patients with anterior circulation acute ischemic stroke due to cardioembolism (CE) or large artery atherosclerosis (LAA) were included. Multivariable regression and interaction analyses were performed to evaluate the association between onset-to-puncture (OTP) time and 90-day functional outcomes and to identify effect modifiers. Results Among 4,719 patients (mean age 72.0 years; 42.9% women; median NIHSS 15), longer OTP time was associated with lower odds of 90-day functional independence (adjusted OR per hour, 0.97; 95% CI, 0.96–0.98; p =0.001). The impact of OTP time varied by stroke characteristics. CE etiology, MCA occlusion, higher NIHSS, and male sex were associated with greater time sensitivity. In CE strokes, each hour of delay reduced the odds of functional independence by 4% (aOR, 0.96; 95% CI, 0.94–0.97; p <0.001), whereas no significant association was observed in LAA strokes (P _interaction =0.028). Conclusion The association between EVT timing and functional outcome varies according to stroke etiology and clinical characteristics, highlighting heterogeneity in time–outcome relationships among EVT-treated patients and providing observational insight into outcome variability in extended treatment windows.