Journal of Capital Medical University ›› 2026, Vol. 47 ›› Issue (1): 62-69.doi: 10.3969/j.issn.1006-7795.2026.01.008

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

Yang Xiao1,2,3, Wang Anxin1, 2, 3, 4, Xu Qin1,2,3,4, Zhou Quan1,2,3,4, Wang Yongjun1,2,3*   

  1. 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).

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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

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