摘要
目的探讨限制平均生存时间(restricted mean survival time,RMST)的原理及其在脑血管病研究中的应用。方法RMST是一种稳健的生存分析方法,在满足比例风险(proportional hazards,PH)假设时可作为Cox比例风险模型的有益补充,在不满足PH假设时可作为替代方法。根据PH假设检验结果,本研究对主要结局分别采用Cox比例风险模型和RMST方法进行分析。以氯吡格雷用于急性非致残性脑血管事件高危人群的疗效研究-Ⅱ(Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular EventsⅡ,CHANCE-2)为例,计算替格瑞洛-阿司匹林组相比于氯吡格雷-阿司匹林组1年卒中复发的RMST差值;同时在中国国家卒中登记研究-Ⅲ(China National Stroke Registry-Ⅲ,CNSR-Ⅲ)中,探讨降压治疗对脑血管病合并高血压患者5年生存时间的影响。结果在CHANCE-2研究中,PH假设成立,相比于氯吡格雷-阿司匹林组,Cox回归提示替格瑞洛-阿司匹林组1年卒中复发风险下降约20%(HR=0.805,95%CI:0.682~0.949),RMST分析进一步显示,替格瑞洛-阿司匹林组在1年随访期内平均无卒中复发时间可延长约6.646 d(341.316 d vs 334.755 d,P<0.05)。在CNSR-Ⅲ研究中,PH假设不成立,多变量调整的RMST分析表明降压治疗可在5年随访期内为脑血管病合并高血压患者平均延长17.455 d生存时间,倾向性评分匹配后观察到类似结果(ΔRMST=22.883 d,P=0.011)。结论RMST不仅能在比例风险假设不满足时提供稳健的效应估计,还能以直观的时间尺度呈现临床获益,在脑血管病临床研究中具有重要的应用价值。
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.
作者
吕宗政
胥芹
张怡君
孟霞
王安心
Lyu Zongzheng;Xu Qin;Zhang Yijun;Meng Xia;Wang Anxin(National Clinical Research Center for Neurological Disease,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Department of Epidemiology,Beijing Neurosurgical Institute,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Department of Clinical Epidemiology and Clinical Trial,Capital Medical University,Beijing 100070,China)
出处
《首都医科大学学报》
北大核心
2026年第1期30-36,共7页
Journal of Capital Medical University
基金
国家重点研发计划项目(2022YFC3501100)
国家自然科学基金项目(82504483)。
