Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update

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).

Figure 1

Algorithm for suggested clinical actions based on CYP2C19 genotype when considering treatment with clopidogrel for ACS patients undergoing PCI (ACS/PCI). ¹Other rare CYP2C19 genotypes exist beyond those illustrated (see Supplementary Materials and Methods online for other genotypes and frequencies). ²Note that prasugrel and ticagrelor are recommended only when not contraindicated clinically. ACS, acute coronary syndrome; EM, extensive metabolizer; IM, intermediate metabolizer; PCI, percutaneous coronary intervention; PM, poor metabolizer; UM, ultrarapid metabolizer.