JACC. Asia · 2025
CYP2C19 Polymorphism and Clopidogrel Efficacy in Long-Term Outcomes of Large-Artery Atherosclerotic Stroke: The NCVC Genome Registry.
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Yoshimoto Takeshi, Hattori Yorito, Ishiyama Hiroyuki, Nakaoku Yuriko, Ogata Soshiro, Abe Soichiro, Ninomiya Kenji, Nishimura Kunihiro, Ihara Masafumi
Аннотация
BACKGROUND: CYP2C19 polymorphisms influence clopidogrel metabolism, which may influence long-term stroke prognosis.
OBJECTIVES: The authors sought to investigate whether CYP2C19 polymorphisms were associated with long-term recurrent ischemic events in patients with acute ischemic stroke due to large-artery atherosclerosis (LAA).
METHODS: The present study, comprising a sub-data set from the National Cerebral and Cardiovascular Center Genome Registry-a data registry from a multicenter, prospective, observational study-enrolled patients with LAA stroke within 7 days of stroke onset who consented to genotyping of CYP2C19 polymorphism between 2004 and 2022. Based on CYP2C19 polymorphisms, participants were assigned to 1 of 3 groups: extensive metabolizers (∗1/∗1), intermediate metabolizers (∗1/∗2, ∗1/∗3), and poor metabolizers (∗2/∗2, ∗2/∗3, ∗3/∗3). The primary endpoint was the recurrence of symptomatic ischemic stroke/transient ischemic attack.
RESULTS: Among 369 participants with LAA stroke (96 females [26.0%]; age, median [Q1-Q3], 74 [65-80] years) and a median follow-up of 5.1 years, poor or intermediate metabolizers (PM/IMs) (n = 164) had a significantly higher risk of recurrent symptomatic ischemic stroke transient ischemic attack than extensive metabolizers (n = 205) (adjusted HR: 2.33; 95% CI: 1.28-4.24). Furthermore, restricting the analysis to patients taking clopidogrel, PM/IMs exhibited a similarly significant risk (adjusted HR: 5.26; 95% CI: 1.87-14.56).
CONCLUSIONS: In patients with LAA stroke, CYP2C19 PM/IMs had a significantly higher long-term recurrence rate of ischemic events than extensive metabolizers.
OBJECTIVES: The authors sought to investigate whether CYP2C19 polymorphisms were associated with long-term recurrent ischemic events in patients with acute ischemic stroke due to large-artery atherosclerosis (LAA).
METHODS: The present study, comprising a sub-data set from the National Cerebral and Cardiovascular Center Genome Registry-a data registry from a multicenter, prospective, observational study-enrolled patients with LAA stroke within 7 days of stroke onset who consented to genotyping of CYP2C19 polymorphism between 2004 and 2022. Based on CYP2C19 polymorphisms, participants were assigned to 1 of 3 groups: extensive metabolizers (∗1/∗1), intermediate metabolizers (∗1/∗2, ∗1/∗3), and poor metabolizers (∗2/∗2, ∗2/∗3, ∗3/∗3). The primary endpoint was the recurrence of symptomatic ischemic stroke/transient ischemic attack.
RESULTS: Among 369 participants with LAA stroke (96 females [26.0%]; age, median [Q1-Q3], 74 [65-80] years) and a median follow-up of 5.1 years, poor or intermediate metabolizers (PM/IMs) (n = 164) had a significantly higher risk of recurrent symptomatic ischemic stroke transient ischemic attack than extensive metabolizers (n = 205) (adjusted HR: 2.33; 95% CI: 1.28-4.24). Furthermore, restricting the analysis to patients taking clopidogrel, PM/IMs exhibited a similarly significant risk (adjusted HR: 5.26; 95% CI: 1.87-14.56).
CONCLUSIONS: In patients with LAA stroke, CYP2C19 PM/IMs had a significantly higher long-term recurrence rate of ischemic events than extensive metabolizers.