Genetic Basis for Clopidogrel Resistance

Clopidogrel (Plavix) is one of the most widely prescribed drugs worldwide. It usually is administered to prevent thrombosis in patients who are undergoing coronary stent placement and in those with cerebral and peripheral ischemic vascular disease. Clopidogrel inhibits the platelet P2Y12 adenosine diphosphate (ADP) receptor, but about 25% of patients who are treated with standard doses of this drug are resistant to its platelet-inhibitory effects. Most importantly, the failure of clopidogrel to inhibit platelet function is associated with high risk for recurrent ischemic events.

Clopidogrel is metabolized by cytochrome P₄₅₀ isoenzymes, and the clopidogrel metabolite binds irreversibly to the platelet receptor to inhibit platelet function. Wi…