Abstract 2220: Number of Co-Administered Cytochrome P450 3A4 (CYP3A4) Substrates or Inhibitors is Independent Predictor of Atherothrombotic Events in Patients Taking Clopidogrel
Background: Clopidogrel is a prodrug requiring metabolism by cytochrome P450 (CYP) 3A isoenzymes in order to be active. CYP3A is responsible for metabolism of most drugs and is the cause of many drug interactions. It is controversial whether clopidogrel interacts with CYP3A inhibitors or substrates. We investigated the influence of co-administered CYP3A inhibitors or substrates on the drug interaction of clopidogrel.
Methods : We compared clinical outcomes of 348 patients treated with clopidogrel after successful coronary angioplasty with bare metal stent implantation according to their number of co-administered CYP3A metabolizers (lipophilic statins, metoprolol, diltiazem, nifedipine, cimetidine and losartan). The end point was a composite of atherothrombotic events (cardiac death, myocardial infarction (MI) and nonhemorrhagic cerebral infarction).
Results: Six months clinical follow-up data were available for all patients. During this period, atherothrombotic events occurred in 17 patients (4.9%). Patients had taken 0.93 ± 0.74 of CYP metabolizers. The number of CYP3A metabolizers was the only independent predictor of atherothrombotic events in patients taking clopidogrel (for every increase in number, odds ratio 2.25, 95% confidence interval 1.15 ± 4.38) in the multivariate analysis including age, sex, diabetes, hypertension, hypercholesterolemia, previous MI, clinical diagnosis, left ventricular ejection fraction, stent size, multi-vessel disease, multi-vessel intervention and the number of co-administered CYP3A metabolizers.
Conclusion: Multiple medications which undergo metabolism via CYP3A system may interact with clopidogrel and may inhibit the protective effect of clopidogrel from atherothrombotic events.