Association of CYP2C19 Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke

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  • Tanaka Tomotaka
    Department of Neurology, National Cerebral and Cardiovascular Center
  • Yamagami Hiroshi
    Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center Department of Neurology, Kobe City Medical Center General Hospital
  • Ihara Masafumi
    Department of Neurology, National Cerebral and Cardiovascular Center
  • Miyata Toshiyuki
    Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center
  • Miyata Shigeki
    Department of Clinical Laboratory Medicine, National Cerebral and Cardiovascular Center
  • Hamasaki Toshimitsu
    Department of Data Science, National Cerebral and Cardiovascular Center
  • Amano Shu
    Department of Mathematics and Statistics, Amherst College
  • Fukuma Kazuki
    Department of Neurology, National Cerebral and Cardiovascular Center
  • Yamamoto Haruko
    Center for Advancing Clinical and Translational Sciences, National Cerebral and Cardiovascular Center
  • Nakagawara Jyoji
    Department of Neurosurgery, National Cerebral and Cardiovascular Center
  • Furui Eisuke
    Department of Stroke Neurology, Kohnan Hospital
  • Uchiyama Shinichiro
    Department of Neurology, Tokyo Women’s Medical University International University of Health and Welfare, Sanno Hospital and Sanno Medical Center
  • Hyun Boohan
    Department of Cerebrovascular Disease, NHO Osaka National Hospital
  • Yamamoto Yasumasa
    Department of Neurology, Kyoto Second Red Cross Hospital
  • Manabe Yasuhiro
    Department of Neurology, NHO Okayama Medical Center
  • Ito Yasuhiro
    Department of Neurology, TOYOTA Memorial Hospital
  • Fukunaga Ryuzo
    Department of Cerebrovascular Disease, Hoshigaoka Medical Center
  • Abumiya Takeo
    Department of Neurosurgery, Hokkaido Neurosurgical Memorial Hospital
  • Yasaka Masahiro
    Department of Cerebrovascular Medicine and Neurology, NHO Kyushu Medical Center
  • Kitagawa Kazuo
    Department of Neurology, Tokyo Women’s Medical University Department of Neurology, Osaka University Graduate School of Medicine
  • Toyoda Kazunori
    Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center
  • Nagatsuka Kazuyuki
    Department of Neurology, National Cerebral and Cardiovascular Center

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タイトル別名
  • Association of <i>CYP2C19</i> Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke

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抄録

<p>Background:CYP2C19variants are associated with the antiplatelet effects of clopidogrel against recurrent cardiovascular events. However, it remains unknown whether the elapsed time from stroke onset affects the relationship between the genetic variants and such events. To address this, we conducted a prospective cohort study to determine the effect ofCYP2C19variants on clinical outcomes in the chronic phase.</p><p>Methods and Results:In total, 518 Japanese non-acute stroke patients treated with clopidogrel were registered at 14 institutions. Patients were classified into 3 clopidogrel-metabolizing groups according toCYP2C19genotype: extensive metabolizer (EM:*1/*1), intermediate metabolizer (IM:*1/*2or*1/*3), and poor metabolizer (PM:*2/*2,*2/*3, or*3/*3). Antiplatelet effects of clopidogrel were assessed by adenosine diphosphate (ADP)-induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. The endpoint was composite cerebrocardiovascular events (CVEs). In 501 successfully followed-up patients, the median time from index stroke to enrollment was 181 days. There were 28 cardiovascular and 2 major bleeding events. There were no significant differences in the rates of cardiovascular events among the groups.</p><p>Conclusions:Despite associations betweenCYP2C19variants and on-clopidogrel platelet reactivity, there was no significant difference in rates of CVEs in the chronic stroke phase among the 3 clopidogrel-metabolizing groups ofCYP2C19variants.</p>

収録刊行物

  • Circulation Journal

    Circulation Journal 83 (6), 1385-1393, 2019-05-24

    一般社団法人 日本循環器学会

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