Lack of clopidogrel–CYP3A4 statin interaction in patients with acute coronary syndrome

OBJECTIVE: To assess a clinically significant interaction between cytochrome P450 3A4 (CYP3A4) metabolised statin and clopidogrel. DESIGN: Prospective single centre cohort study. SETTING: Academic teaching hospital in the USA. PATIENTS: 1651 patients presenting with acute coronary syndromes between January 1999 and February 2003 were studied. Data on baseline demographics, co-morbidities, and in-hospital management were collected. MAIN OUTCOME MEASURE: Association of CYP3A4 metabolised statin and clopidogrel use with in-hospital and six month mortality. The impact of the combined use of a CYP3A4 statin and clopidogrel on six month mortality and major adverse cardiac events was analysed by a risk adjusted logistic regression model. RESULTS: The odds ratios for six month mortality were: for CYP3A4 statin, 0.43 (95% confidence interval (CI) 0.27 to 0.71, p = 0.0009); for CYP3A4 statin plus clopidogrel, 0.36 (95% CI 0.23 to 0.60, p < 0.001); for non-CYP3A4 statin, 0.22 (95% CI 0.08 to 0.59, p = 0.002); and for non-CYP3A4 statin plus clopidogrel, 0.22 (95% CI 0.06 to 0.75, p = 0.016). CONCLUSIONS: Use of a combination of a CYP3A4 statin plus clopidogrel was associated with lower six month mortality and morbidity in patients with acute coronary syndromes. There was no significant difference in clinical benefit between a CYP3A4 statin and a non-CYP3A4 statin when used in conjunction with clopidogrel. This suggests that the proposed interaction is probably an ex vivo phenomenon and may not be clinically relevant.