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Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 Genotype and Clopidogrel Therapy: 2013 Update

Clinical Pharmacology & Therapeutics · 2013 · Vol. 94(3) · pp. 317–323
Stuart A. ScottKatrin SangkuhlCatherine M. SteinJean‐Sébastien HulotJessica L. MegaD M RodenTeri E. KleinMarc S. SabatineJulie A. JohnsonAlan R. Shuldiner

Abstract

Cytochrome P450 (CYP)2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 loss-of-function alleles impair formation of active metabolites, resulting in reduced platelet inhibition. In addition, CYP2C19 loss-of-function alleles confer increased risks for serious adverse cardiovascular (CV) events among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI). Guideline updates include emphasis on appropriate indication for CYP2C19 genotype-directed antiplatelet therapy, refined recommendations for specific CYP2C19 alleles, and additional evidence from an expanded literature review (updates at http://www.pharmgkb.org).

Antiplatelet Therapy and Cardiovascular DiseasesDiabetes Treatment and ManagementSynthesis of β-Lactam CompoundsCYP2C19ClopidogrelMedicinePercutaneous coronary interventionPharmacogeneticsProdrugPharmacologyGuidelineConventional PCIP2Y12

MeSH terms

ClopidogrelAryl Hydrocarbon HydroxylasesGenetic TestingGenotypeHumansPlatelet Aggregation InhibitorsTiclopidineGenetic VariationRisk AssessmentCytochrome P-450 CYP2C19

Funding

  • AstraZeneca
  • Sanofi
  • National Institutes of Health
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