{"title":"CYP2C19多态性和氯吡格雷对大动脉粥样硬化性卒中长期预后的影响：NCVC基因组登记","authors":"Takeshi Yoshimoto, Yorito Hattori, Hiroyuki Ishiyama, Yuriko Nakaoku, Soshiro Ogata, Soichiro Abe, Kenji Ninomiya, Kunihiro Nishimura, Masafumi Ihara","doi":"10.1016/j.jacasi.2025.07.020","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>CYP2C19 polymorphisms influence clopidogrel metabolism, which may influence long-term stroke prognosis.</p><p><strong>Objectives: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>In patients with LAA stroke, CYP2C19 PM/IMs had a significantly higher long-term recurrence rate of ischemic events than extensive metabolizers.</p>","PeriodicalId":73529,"journal":{"name":"JACC. Asia","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CYP2C19 Polymorphism and Clopidogrel Efficacy in Long-Term Outcomes of Large-Artery Atherosclerotic Stroke: The NCVC Genome Registry.\",\"authors\":\"Takeshi Yoshimoto, Yorito Hattori, Hiroyuki Ishiyama, Yuriko Nakaoku, Soshiro Ogata, Soichiro Abe, Kenji Ninomiya, Kunihiro Nishimura, Masafumi Ihara\",\"doi\":\"10.1016/j.jacasi.2025.07.020\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>CYP2C19 polymorphisms influence clopidogrel metabolism, which may influence long-term stroke prognosis.</p><p><strong>Objectives: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>In patients with LAA stroke, CYP2C19 PM/IMs had a significantly higher long-term recurrence rate of ischemic events than extensive metabolizers.</p>\",\"PeriodicalId\":73529,\"journal\":{\"name\":\"JACC. Asia\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JACC. Asia\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jacasi.2025.07.020\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACC. Asia","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.jacasi.2025.07.020","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
CYP2C19 Polymorphism and Clopidogrel Efficacy in Long-Term Outcomes of Large-Artery Atherosclerotic Stroke: The NCVC Genome Registry.
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.
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