Role of CYP2C19 alleles in the management of recurrent ischemic stroke.

Abstract

CYP2C19 is the primary enzyme involved in the activation of clopidogrel, an antiplatelet agent used for secondary stroke prevention. An individual's CYP2C19 alleles are used to understand their CYP2C19-clopidogrel metabolizer phenotype. Single nucleotide polymorphisms of the CYP2C19 gene result in altered metabolism of this prodrug. Three ischemic stroke cases were treated with clopidogrel. Despite confirming adequate drug exposure, medication adherence, and ruling out drug-drug interactions, all had recurrent ischemic stroke. Each case had a CYP2C19 *2/*17 genotype, categorizing them as intermediate clopidogrel metabolizers. Even with the gain-of-function allele, the loss-of-function allele resulted in lack of prodrug activation, leading to decreased efficacy in platelet inhibition. These cases illustrate the importance of a thoughtful approach to secondary stroke prevention and demonstrate the utility of pharmacogenomic testing in clopidogrel hyporesponders. Recognition of the importance of CYP2C19 genotyping has the potential to enable better selection of appropriate secondary prevention strategies.