日本循環器學誌 Association of <i>CYP2C19</i> Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke

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Abstract

<p><b><i>Background:</i></b><i>CYP2C19</i>variants 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 of<i>CYP2C19</i>variants on clinical outcomes in the chronic phase.</p><p><b><i>Methods and Results:</i></b>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 to<i>CYP2C19</i>genotype: extensive metabolizer (EM:<i>*1/*1</i>), intermediate metabolizer (IM:<i>*1/*2</i>or<i>*1/*3</i>), and poor metabolizer (PM:<i>*2/*2</i>,<i>*2/*3</i>, or<i>*3/*3</i>). 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><b><i>Conclusions:</i></b>Despite associations between<i>CYP2C19</i>variants 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 of<i>CYP2C19</i>variants.</p>

Journal

  • Circulation Journal

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

    The Japanese Circulation Society

Codes

  • NII Article ID (NAID)
    130007652780
  • NII NACSIS-CAT ID (NCID)
    AA11591968
  • Text Lang
    ENG
  • ISSN
    1346-9843
  • NDL Article ID
    029688490
  • NDL Call No.
    Z54-B860
  • Data Source
    NDL  J-STAGE 
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