Abstract: Objective  To explore the principle of restricted mean survival time (RMST) and its application in cerebrovascular disease research. Methods  RMST is employed as a robust method for survival analysis, providing an alternative to Cox proportional hazards （PH） model when the PH assumption is violated and a complement when it was satisfied. In this study, outcomes were analyzed by Cox PH model or RMST method according to the results of the PH assumption test. The Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events Ⅱ (CHANCE-2) trial was used to assess the difference in 1-year RMST for stroke recurrence between the ticagrelor-aspirin and clopidogrel-aspirin groups. The  China National Stroke Registry-Ⅲ (CNSR-Ⅲ) was used to examine the effect of antihypertensive therapy on 5-year survival among patients with cerebrovascular disease and hypertension. Results  In CHANCE-2, the PH assumption was satisfied. Compared with clopidogrel-aspirin, Cox regression showed that ticagrelor-aspirin reduced the risk of recurrent stroke by 20% (HR=0.805, 95% CI: 0.682－0.949), and RMST analysis further indicated an approximate 6.646－d prolongation in the mean stroke-free survival time over one year (341.316 vs 334.755 d, P < 0.05). In CNSR-Ⅲ, the PH assumption was violated. Multivariable-adjusted RMST analysis demonstrated that antihypertensive treatment extended overall survival by 17.455  d over five years in patients with cerebrovascular disease and hypertension, with similar findings after propensity score matching (ΔRMST=22.883  d, P < 0.05). Conclusion  RMST yield robust estimates and interpretable effect measures beyond the PH assumption, highlighting its significance in cerebrovascular disease research.

Key words: restricted mean survival time, survival analysis, proportional hazards assumption, cerebrovascular disease, CHANCE-2, CNSR-Ⅲ