Can we override clopidogrel resistance?

Clopidogrel, a thienopyridine antiplatelet agent, has been used alone or in association with aspirin to prevent vascular complications in atherothrombotic patients. It is also, in combination with aspirin, the key treatment to prevent stent thrombosis in patients who have undergone percutaneous coronary intervention. It is estimated that >40 million patients worldwide receive clopidogrel. Recent investigations into genetic mechanisms that influence clopidogrel efficacy suggest that a common variant present in ≈30% of whites has the potential to identify patients with a deficient clopidogrel metabolic activation who are consequently at risk of recurrent cardiovascular events, including stent thrombosis.1–3 Stent thrombosis is the most serious complication of coronary stent implantation, often leading to empiric modifications of antiplatelet treatments, although stent thrombosis pathogenesis is complex and the weight of the various factors involved is not known.4 We report 7 recent cases of stent thrombosis with demonstrated platelet resistance to clopidogrel, and we describe a novel clinical approach using pharmacodynamic and genetic information to override clopidogrel resistance. ### Patient Selection and Characteristics The clinical characteristics of 7 patients who presented with stent thrombosis on clopidogrel treatment (75 mg maintenance dose [MD]) are presented in the Table. Stent thrombosis was angiographically proven in all patients and occurred on days 1, 3, 5, 6 (2 patients), 11, and 70, with a median time from stent implantation to stent occlusion of 6 days (interquartile range, 4 to 8.5 days). Clinical presentation was ST-elevation myocardial infarction in all cases, and 4 of 7 patients had a history of myocardial infarction. Stent thrombosis occurred in 6 patients with a bare metal stent and 1 patient with a drug-eluting stent. Primary percutaneous coronary intervention revascularization of stent thrombosis was performed with a new bare metal stent in 6 patients; in the remaining patient, a drug-eluting stent was implanted. View this table: Table. Baseline Characteristics of the …