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

Lyerly MJ, Bartlett K, Albright KC. Role of CYP2C19 alleles in the management of recurrent ischemic stroke. Neurology. Clinical practice. 2019 Apr 1; 9(2):140-144.

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Abstract:

Purpose of review: CYP2C19 is the primary enzyme involved in the activation of clopidogrel, an antiplatelet agent used for secondary stroke prevention. An individual''s alleles are used to understand their -clopidogrel metabolizer phenotype. Single nucleotide polymorphisms of the gene result in altered metabolism of this prodrug. Recent findings: 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 *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. Summary: 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 genotyping has the potential to enable better selection of appropriate secondary prevention strategies.