Oncotarget

Research Papers:

The secondary prevention of stroke according to cytochrome P450 2C19 genotype in patients with acute large-artery atherosclerosis stroke

Xingyang Yi, Jing Lin _, Ju Zhou, Yanfeng Wang, Ruyue Huang and Chun Wang

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Oncotarget. 2018; 9:17725-17734. https://doi.org/10.18632/oncotarget.24877

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Abstract

Xingyang Yi1, Jing Lin2, Ju Zhou1, Yanfeng Wang1, Ruyue Huang2 and Chun Wang1

1Department of Neurology, People’s Hospital of Deyang City, Deyang 618000, Sichuan, China

2Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, Zhejiang, China

Correspondence to:

Jing Lin, email: [email protected]; [email protected]

Keywords: clopidogrel; aspirin; ischemic stroke; CYP2C19 polymorphism; outcomes

Received: November 01, 2017    Accepted: February 28, 2018    Published: April 03, 2018

ABSTRACT

Purpose: To investigated the effectiveness of antiplatelet agents for the secondary prevention of stroke according to CYP2C19 genotype in patients with ischemic stroke (IS).

Methods: Between August 2009 and December 2011, 570 acute IS patients with acute large-artery atherosclerosis were randomly assigned to receive either combined clopidogrel and aspirin for the first 30 day, and clopidogrel thereafter (clopidogrel group, n=284) or aspirin monotherapy (aspirin group, n=286). CYP2C19 genotypes were measured and masked until the end-of-study. The primary outcome was a composite of IS, transient ischemic attack (TIA), myocardial infarction (MI), and death.

Results: During the 5 years follow-up, the primary outcome occurred in 105 patients (18.4%) (71 had IS, 10 had TIA, 12 had MI, and 12 died). There were no significant differences in the primary outcome between clopidogrel group and aspirin group (16.5% vs. 20.3%) or between carriers of the CYP2C19 reduced-function alleles and noncarriers (21.8% vs.15.7%). In patients with aspirin therapy, CYP2C19 polymorphism was not associated with the primary outcome. However, in patients treated with clopidogrel, carriers of at least one CYP2C19 reduced-function allele had a 3-fold higher adjusted risk for primary outcome compared with noncarriers (95% confidence interval, 1.23 to 8.74).

Conclusions: Among IS patients treated with clopidogrel, carriers of a reduced-function CYP2C19 allele had a significantly higher rate of adverse vascular events than did noncarriers. It should avoid prescribing clopidogrel to these patients with known CYP2C19 polymorphisms.


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