Pharmacogenetics of Clopidogrel

A 58-year-old male was presented with an ST-elevation inferior myocardial infarction. Emergency medical services administered 325 mg of aspirin and sublingual nitroglycerin en route to the emergency room.In the emergency room, the patient received 600 mg of clopidogrel and a heparin bolus. Coronary angiography revealed complete occlusion of the distal right coronary artery with thrombus. Intravenous eptifibatide was given at the start of the percutaneous coronary intervention (PCI). Intravascular ultrasound demonstrated significant soft atheroma and ruptured plaque in the distal right coronary artery at the crux. A drug-eluting stent was deployed with an excellent angiographic result.Postintervention, the patient’s chest pain and ECG demonstrated complete resolution of the previous ischemic changes. Approximately 11 hours after being treated in the emergency room, the patient developed recurrent chest pain. He was restarted on eptifibatide and heparin, and repeat coronary angiography demonstrated total occlusion at the origin of the right coronary artery stent (Figure 1).Figure 1. Coronary angiogram demonstrating an occluded mid right coronary artery because of stent thrombosis.Thrombectomy was performed, removing huge amounts of atherothrombotic material (Figure 2). Intravascular ultrasound did not demonstrate stent edge dissection or stent malapposition.Figure 2. Coronary thrombus material extracted from the right coronary artery after thrombectomy.A drug-eluting stent with 1-mm overlap with the distal edge of the previous stent was deployed. The patient was felt to have failed clopidogrel therapy and was transitioned to prasugrel therapy. The patient was screened for genetic variants in CYP2C19 , the gene encoding the cytochrome P450 enzyme CYP2C19 that metabolizes clopidogrel.A Luminex assay using a polymerase chain reaction was used to test for the presence or absence of CYP2C19 * 17 , * 4 , * 8 , * 6 , * 9 , * 3 , * 10 , * 2 , * 7 , and * …