Gene Variants Affect Metabolism of Clopidogrel — And Clinical Outcomes

Clopidogrel (Plavix) is prescribed widely to patients with acute coronary syndromes (ACS) and those who have received stents. Clopidogrel is metabolized by the cytochrome P₄₅₀ system: An active clopidogrel metabolite impairs platelet activity. In new studies, three different teams independently reported that “reduced-function alleles” of the CYP2C19 gene that interfere with production of the active metabolite are associated with worse clinical outcomes.

A U.S. team found that, in patients with these “reduced-function alleles,” concentrations of the active metabolite, as well as platelet inhibition, were lower than in patients with two normal alleles. In a study of 1477 patients with ACS, those who carried at least one reduced-function allele…