Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy

Abstract

CYP2C19 is one of the principal enzymes involved in the bioactivation of the antiplatelet prodrug clopidogrel. A common loss-of-function allele, CYP2C19*2 (c.681G>A; rs4244285), is associated with increased risk for serious adverse cardiovascular events in both heterozygous and homozygous patients (~25–50% of the population) with acute coronary syndromes (ACSs) who are receiving clopidogrel, particularly among those undergoing percutaneous coronary intervention (PCI). We provide evidence from published literature and guidelines for CYPC19 genotype–directed antiplatelet therapy (periodically updated at http://www.pharmgkb.org).

Figure 1

Algorithm for suggested clinical actions based on CYP2C19 genotype in patients with acute coronary syndromes initiating antiplatelet therapy. ACS, acute coronary syndrome; EM, extensive metabolizer; IM, intermediate metabolizer; PCI, percutaneous coronary intervention; PM, poor metabolizer; UM, ultrarapid metabolizer. Other rare CYP2C19 genotypes exist apart from those illustrated (see Supplementary Data online for other genotypes and frequencies). Higher-dose clopidogrel has not been adequately studied at the time of this writing but may improve platelet function in a subset of IMs and PMs (Supplementary Table S8 online).Note that prasugrel is recommended only when its use is not clinically contraindicated.