Why the study?
Do CYP2C19 loss-of-function alleles reduce the antiplatelet effect and clinical efficacy of clopidogrel in patients with acute ischemic stroke?
Do CYP2C19 loss-of-function alleles reduce the antiplatelet effect and clinical efficacy of clopidogrel in patients with acute ischemic stroke?
CYP2C19 loss-of-function alleles are associated with reduced antiplatelet response to clopidogrel and worse clinical outcomes in patients with acute ischemic stroke.
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May attenuate clopidogrel efficacy in acute ischemic stroke; hypothesis-generating for genotype-guided trials.
BACKGROUND AND PURPOSE: Little research regarding genotypes and clopidogrel response related to acute ischemic stroke has been published. This study was conducted to investigate whether the polymorphisms of receptors or enzymes involved in the metabolic process of clopidogrel affect clopidogrel response and prognosis related to acute stroke. METHODS: A total of 259 patients with acute ischemic stroke were enrolled in this study; all received follow-up evaluations 3 and 6 months after clopidogrel treatment. CYP2C19, CYP3A4, and P2Y12 were screened. The adenosine diphosphate-induced platelet aggregation test, the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were used, and blood vascular events were evaluated. RESULTS: The difference before and after clopidogrel treatment on adenosine diphosphate-induced platelet aggregation was significantly smaller in patients carrying 1 or 2 CYP2C19 loss-of-function alleles (*2, *3) compared with patients carrying none. Patients with none had better outcomes than patients with CYP2C19 loss-of-function alleles, as demonstrated by NIHSS and mRS scores at 3 and 6 months after treatment. Regression analysis showed that CYP2C19 was an independent predictor of clopidogrel resistance. CONCLUSIONS: CYP2C19 genotypes had significant impact on clopidogrel response and prognosis of patients with stroke. Clinical Trial Registration Information- URL: http://www.chictr.org/. Unique Identifier: ChiCTR-OCH-12002681.
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Jia et al. (2013) studied this question.
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