Effect of CYP2C19*2 and *3 on clinical outcome in ischemic stroke patients treated with clopidogrel.

BACKGROUND: Despite clopidogrel has been widely applied to patients with ischemic stroke combined with aspirin, decreased metabolic activation of clopidogrel still occurs because of genetic variations in CYP2C19.

METHODS: Three hundred twenty-one patients completed a genetic test for CYP2C19 loss of function (LOF) alleles in hospital. Cox regression models were used to assess the relationship between CYP2C19 genotypes with the primary endpoint, which was a composite of nonfatal ischemic stroke, myocardial infarction, or vascular death. Functional outcome was measured by the modified Rankin Scale (mRS) at 3months, 6months and 12months intervals. Binary logistic regression was used to analyze the correlation between poor functional outcome and CYP2C19 LOF alleles.

RESULTS: The CYP2C19 LOF alleles were independently associated with the primary endpoint. There was no significant association between poor functional outcome and CYP2C19 LOF allele (*2 and *3) in overall patients. After the participants were stratified by stent treatment into two groups, the polymorphisms of CYP2C19 had significant impact on poor prognosis at 3months and 6months but not at 12months in patients without stent. No correlation was found in patients with stent.

CONCLUSIONS: The CYP2C19 LOF alleles may increase the recurrent risk of ischemic events. The polymorphisms of CYP2C19 may be predictors of poor functional outcome of patients without stent, and the effect may be weakened by time.