胰岛素抵抗对基因型指导的双联抗血小板治疗轻型卒中或TIA疗效和安全性的影响

doi:10.3969/j.issn.1006-7795.2026.01.008

首都医科大学学报 ›› 2026, Vol. 47 ›› Issue (1): 62-69.doi: 10.3969/j.issn.1006-7795.2026.01.008

胰岛素抵抗对基因型指导的双联抗血小板治疗轻型卒中或TIA疗效和安全性的影响

杨笑^1,2,3,王安心^1,2,3,4,胥芹^1,2,3,4,周全^1,2,3,4,王拥军^1,2,3*

1.首都医科大学附属北京天坛医院神经病学中心，北京 100070；2.首都医科大学附属北京天坛医院，国家神经系统疾病临床医学研究中心，北京 100070；3.首都医科大学临床流行病学与临床试验学系，北京 100070；4.首都医科大学附属北京天坛医院，北京市神经外科研究所流行病学研究室，北京 100070

收稿日期:2025-10-20 修回日期:2025-11-11 出版日期:2026-02-21 发布日期:2026-02-02
通讯作者: 王拥军 E-mail:yongjunwang@ncrcnd.org.cn
基金资助:
北京市医院管理中心临床医学发展专项项目(ZLRK202312)。

Impact of insulin resistance on the efficacy and safety of genotype-guided dual antiplatelet therapy in minor stroke or transient ischemic attack

Yang Xiao^1,2,3, Wang Anxin^{1, 2, 3, 4}, Xu Qin^1,2,3,4, Zhou Quan^1,2,3,4, Wang Yongjun^1,2,3*

1 .Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China ；2 .National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China；3. Department of Clinical Epidemiology and Clinical Trial, Capital Medical University, Beijing 100070, China；4 .Department of Epidemiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China

Received:2025-10-20 Revised:2025-11-11 Online:2026-02-21 Published:2026-02-02
Supported by:
This study was supported by Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (ZLRK202312).

摘要/Abstract

摘要： 目的在携带CYP2C19功能缺失等位基因的轻型卒中或短暂性脑缺血发作(transient ischemic attack, TIA)患者中，探讨胰岛素抵抗对替格瑞洛－阿司匹林与氯吡格雷－阿司匹林在降低卒中复发风险的疗效和安全性方面的影响。方法基于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 Events Ⅱ，CHANCE-2）试验，纳入基线三酰甘油、空腹血糖、身高、体质量、腰围数据资料完整的患者。以三酰甘油葡萄糖－体质量指数 (triglyceride-glucose-body mass index, TyG-BMI)、三酰甘油葡萄糖－腰围(TyG-waist circumference, TyG-WC)、三酰甘油葡萄糖－腰高比(TyG-waist-to-height ratio, TyG-WHtR)作为胰岛素抵抗替代指标，按各指数的中位数将患者划分为高、低胰岛素抵抗亚组。主要疗效指标和安全性指标分别为90 d内卒中复发和中重度出血。结果在高TyG-WC和高TyG-WHtR组中，替格瑞洛－阿司匹林较氯吡格雷－阿司匹林显著降低卒中复发风险(P<0.05)，风险比(hazard ratio, HR)分别为0.70 (95% CI: 0.53－0.92)和0.74 (95% CI: 0.56~0.97)；在高TyG-BMI、低TyG-WC、低TyG-WHtR和低TyG-BMI亚组中，替格瑞洛－阿司匹林虽显示疗效优势，但差异无统计学意义(P>0.05)。各亚组中两治疗组间中重度出血风险差异无统计学意义(P>0.05)。结论以高TyG-WC或高TyG-WHtR为特征的高胰岛素抵抗患者，可能是基于CYP2C19基因型选择替格瑞洛－阿司匹林治疗的敏感人群。

关键词: 胰岛素抵抗, 卒中复发, CHANCE-2试验, 替格瑞洛－阿司匹林, 氯吡格雷－阿司匹林, CYP2C19

Abstract: Objective To explore the impact of insulin resistance on the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in reducing the risk of stroke recurrence in patients with minor stroke or transient ischemic attack (TIA) who carry CYP2C19 loss-of-function alleles. Methods Based on the Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events Ⅱ （CHANCE-2） trial, patients with complete baseline data on triglycerides, fasting plasma glucose, height, weight, and waist circumference (WC) were included. The triglyceride-glucose-body mass index (TyG-BMI), TyG-WC, and TyG-waist-to-height ratio (TyG-WHtR) were used as surrogate markers of insulin resistance. Patients were divided into high and low insulin resistance subgroups according to the median of each index. The primary efficacy and safety outcome were defined as stroke recurrence and moderate or severe bleeding within 90 d. Results In the high TyG-WC and high TyG-WHtR subgroups, ticagrelor-aspirin significantly reduced the risk of stroke recurrence compared with clopidogrel-aspirin(P<0.05), the hazard ratios (HR) were 0.70 (95% CI: 0.53 － 0.92) and 0.74 (95% CI: 0.56 － 0.97), respectively; In the high TyG-BMI, low TyG-WC, low TyG-WHtR, or low TyG-BMI subgroups, ticagrelor-aspirin showed a trend toward better efficacy, but this benefit was not statistically significant (P > 0.05). Additionally, there was no significant difference in the risk of severe and moderate bleeding within 90 d between the two treatment groups across all subgroups (all P > 0.05). Conclusion Patients with high insulin resistance characterized by high TyG-WC or high TyG-WHtR may represent responsive subgroup for ticagrelor-aspirin treatment as determined by their CYP2C19 genotype.

Key words: insulin resistance, stroke recurrence, CHANCE-2 trial, ticagrelor-aspirin, clopidogrel-aspirin, CYP2C19

中图分类号:

R743

杨笑, 王安心, 胥芹, 周全, 王拥军. 胰岛素抵抗对基因型指导的双联抗血小板治疗轻型卒中或TIA疗效和安全性的影响[J]. 首都医科大学学报, 2026, 47(1): 62-69.

Yang Xiao, Wang Anxin , Xu Qin, Zhou Quan, Wang Yongjun. Impact of insulin resistance on the efficacy and safety of genotype-guided dual antiplatelet therapy in minor stroke or transient ischemic attack[J]. Journal of Capital Medical University, 2026, 47(1): 62-69.

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胰岛素抵抗对基因型指导的双联抗血小板治疗轻型卒中或TIA疗效和安全性的影响

Impact of insulin resistance on the efficacy and safety of genotype-guided dual antiplatelet therapy in minor stroke or transient ischemic attack

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