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.