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(Clopidrogen CYP2C19 Genotyping)

Clopidogrel when added to aspirin reduces major vascular events in patients undergoing percutaneous coronary intervention (PCI).1 Recent reports have suggested that common genetic variants involving hepatic cytochrome P450 system enzymes that convert clopidogrel to its active metabolite are associated with an increased risk of cardiovascular events. Specifically, patients who are carriers of 1 or more loss-of- function CYP2C19 alleles (including the *2 and *3 alleles) have reduced conversion of clopidogrel to its active metabolite, decreased platelet inhibition, and an increased risk of myocardial infarction, death, and stent thrombosis compared with noncarriers. Based on these findings and on related pharmacokinetic and pharmacodynamic data (NCT01123824), the United States Food and Drug Administration (FDA) has issued a “black box” warning of reduced effectiveness of clopidogrel in patients who are carriers of 2 loss-of-function alleles (so-called poor metabolizers) and has suggested that affected individuals receive a higher dose of clopidogrel or an alternative antiplatelet agent. This warning has led some investigators to conclude that all patients undergoing PCI with planned clopidogrel therapy should undergo CYP2C19 genetic testing.

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