Dual antiplatelet therapy with aspirin and a thienopyridine is recommended both in patients after acute myocardial infarction (MI) and in patients undergoing percutaneous coronary intervention (PCI) procedures with stenting. Every year in the United States, there are approximately 1.3 million inpatient PCIs and 0.9 million patients who experience an MI. Clopidogrel (trade name Plavix®; Sanofi-Aventis Inc.) is the main thienopyridine prescribed for antiplatelet therapy; in 2009, the Food and Drug Administration (FDA) approved prasugrel (trade name Effient®; Eli Lilly&Co.), which provides another option. Clopidogrel with aspirin is effective at reducing recurrent coronary events and mortality; however, patients have a variable response to clopidogrel, with up to 30% of patients not experiencing complete platelet inhibition. One source of the variable response to clopidogrel is
its pharmacokinetics, as clopidogrel is a prodrug that must be converted to an active metabolite before having any effect. The main enzyme that is responsible for this conversion to the active metabolite is the cytochrome P450 (CYP) enzyme CYP2C19. Many variants of this gene can be found, most of which cause a loss of function of the CYP2C19 enzyme and a few that result in gain of function. Recently, a boxed warning was placed on the clopidogrel prescribing information by the FDA suggesting that alternative treatment or treatment strategies should be considered in patients who are CYP2C19 poor metabolizers. Because of this change in FDA labeling and the availability of prasugrel, a reexamination of CYP2C19 genotyping to determine response to clopidogrel has been performed.