Author:
Lyerly Michael J.,Bartlett Kelly,Albright Karen C.
Abstract
Purpose of reviewCYP2C19 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.Recent findingsThree 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.SummaryThese 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Reference24 articles.
1. Nau DP . Proportion of days covered (PDC) as a preferred method of measuring medication adherence. Research & Performance Measurement. Available at: http://www.pqaalliance.org/files/PDCvsMPRfinal.pdf. Accessed June 12, 2018.
2. Diagnostics Q AccuType CP, Clopidogrel CYP2C19 Genotype. Test Center. 2014. Available at: http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=16924. Accessed June 1, 2018.
3. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update;Scott;Clin Pharmacology Therapeutics,2013
4. Cytochrome p-450 polymorphisms and response to clopidogrel;Mega;New Engl Journal Medicine,2009
5. Concurrent and Predictive Validity of a Self-reported Measure of Medication Adherence
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