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.


METHODS
Prospective single centre cohort study.


METHODS
Academic teaching hospital in the USA.


METHODS
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.


METHODS
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.
Mukherjee
D
D
Division of Cardiology, University of Michigan, Health System, 1500 E Medical Center Drive, Ann Arbor, Michigan 48103-0311, USA. dmukherj@umich.edu
Kline-Rogers
E
E
Fang
J
J
Munir
K
K
Eagle
K A
KA
D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy / Q000401:mortality; D000077144:Clopidogrel; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000401:mortality; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D016019:Survival Analysis; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D013988:Ticlopidine