The first study to show a role for CYP2C19 in bioactivating clopidogrel reported that subjects heterozygous for CYP2C19 loss of function *2 allele generate on average less anti-platelet effects than those with wild-type *1 alleles, but there was overlap between those with the *1/*1 and those with the *1/*2 genotypes.62 Subsequently, a meta-analysis of outcomes after clopidogrel for coronary stenting showed higher rates of in-stent thrombosis and MACE in subjects with CYP2C19 variants.63 The FDA then changed the label for clopidogrel to include a black box warning that if genotype data were available and indicate a CYP2C19 loss of function variant, alternate anti-platelet therapies should be prescribed. As a result of the clinical studies and the black box warning, some centers have adopted routine CYP2C19 screening in subjects scheduled for coronary angiography. Most recently, the University of Florida group reported that switching from clopidogrel to alternate antiplatelet therapies in subjects with CYP2C19 variants reduced MACE risk after stenting.64
