Impact of CYP2C19 Metabolizer Status on Patients With ACS Treated With Prasugrel Versus Clopidogrel

被引：42

作者：

Doll, Jacob A. ^{[1
]}

Neely, Megan L. ^{[2
]}

Roe, Matthew T. ^{[1
,2
]}

Armstrong, Paul W. ^{[3
]}

White, Harvey D. ^{[4
]}

Prabhakaran, Dorairaj ^{[5
]}

Winters, Kenneth J. ^{[6
]}

Duvvuru, Suman ^{[6
]}

Sundseth, Scott S. ^{[7
]}

Jakubowski, Joseph A. ^{[6
]}

Gurbel, Paul A. ^{[8
]}

Bhatt, Deepak L. ^{[9
,10
]}

Ohman, E. Magnus ^{[1
,2
]}

Fox, Keith A. A. ^{[11
]}

机构：

[1] Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA

[2] Duke Clin Res Inst, Durham, NC USA

[3] Univ Alberta, Dept Med, Div Cardiol, Canadian VIGOUR Ctr, Edmonton, AB, Canada

[4] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand

[5] Ctr Chron Dis Control & Publ Hlth Fdn India, New Delhi, India

[6] Eli Lilly & Co, Indianapolis, IN 46285 USA

[7] Cabernet Pharmaceut, Chapel Hill, NC USA

[8] Inova Heart & Vasc Inst, Inova Ctr Thrombosis Res & Drug Dev, Falls Church, VA USA

[9] Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Boston, MA 02115 USA

[11] Univ Edinburgh, British Heart Fdn, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2016年 / 67卷 / 08期

基金：

美国国家卫生研究院;

关键词：

acute coronary syndrome; dual antiplatelet therapy; genetics; platelets; ACUTE CORONARY SYNDROMES; ANTIPLATELET THERAPY; ARTERY-DISEASE; CARDIOVASCULAR OUTCOMES; RESPONSE VARIABILITY; PLATELET INHIBITION; CLINICAL-OUTCOMES; GENOTYPE; POLYMORPHISMS; TRIAL;

D O I：

10.1016/j.jacc.2015.12.036

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Certain alleles of the CYP2C19 gene are associated with higher platelet reactivity and increased ischemic events among patients treated with clopidogrel. However, the relationship of CYP2C19 genotype and outcomes in medically managed patients with acute coronary syndromes (ACS) is not known. OBJECTIVES This study sought to assess the effect of CYP2C19 genotype on ischemic outcomes in patients with ACS initially managed medically without revascularization who were randomized to either clopidogrel or prasugrel. METHODS We classified patients as extensive metabolizers (EM) or reduced metabolizers (RM) based on CYP2C19 genotype and evaluated ischemic outcomes and platelet reactivity. Among 9,326 patients enrolled from 2008 to 2011, 5,736 participated in the genetics cohort; of these, 2,236 had platelet function testing data. RESULTS There was no association between CYP2C19 metabolizer status (EM vs. RM) and the primary composite endpoint of cardiovascular death, myocardial infarction (MI), or stroke (hazard ratio [HR]: 0.86). EM and RM patients had similar rates of the primary endpoint whether treated with prasugrel (HR: 0.82) or clopidogrel (HR: 0.91; p for interaction = 0.495). After adjusting for clinical and treatment variables, EM patients had a lower risk of MI versus RM patients (HR: 0.80), but risks of other outcomes were similar. RM patients had significantly higher mean P2Y(12) reaction units versus EM patients when treated with clopidogrel (39.93), but not with prasugrel (3.87). CONCLUSIONS CYP2C19 metabolizer status is not associated with the composite outcome of cardiovascular death, MI, or stroke in medically managed ACS patients treated with clopidogrel or prasugrel. Our findings do not support routine CYP2C19 genetic testing in this population. ( A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects [TRILOGY ACS]) (C) 2016 by the American College of Cardiology Foundation.

引用

页码：936 / 947

页数：12

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