Investigation of an interaction between statins and clopidogrel after percutaneous coronary intervention: a cohort study.
BACKGROUND
Clopidogrel is an antiplatelet drug that is prescribed after percutaneous coronary intervention (PCI) to prevent stent thrombosis. Previous studies have suggested that some statins may inhibit the antiplatelet effects of clopidogrel via competitive metabolism of its activating enzyme cytochrome P450 3A4 (CYP3A4).


OBJECTIVE
To investigate a possible interaction between statins and clopidogrel after a PCI procedure in a population-based cohort study.


METHODS
A population-based cohort study was carried out between January 2001 and December 2004 using the health insurance databases from Quebec, Canada. The primary endpoint was a composite of death from any cause, myocardial infarction (MI), unstable angina, repeat revascularization and cerebrovascular events. PCI patients >or= 66 years of age were followed from their initial post-discharge clopidogrel prescription until the earliest of study endpoint occurrence, end of clopidogrel exposure or end of study (90 days post discharge). Time-dependent Cox regression analysis was performed.


RESULTS
We identified 10491 patients who were prescribed clopidogrel post-PCI and 43.5% were also prescribed statins at the baseline discharge. During 1793 patient years of follow-up, 623 composite endpoints were observed. Compared to the reference group (non-CYP3A4-metabolized statins), the co-prescription of CYP3A4-metabolized statins (hazard ratio (HR) 1.16, 95% confidence interval (CI) 0.91-1.47), or no statin use (HR 1.22, 95%CI 0.93-1.59) were not statistically associated with an increase in adverse outcomes.


CONCLUSIONS
In this PCI cohort, the association of clopidogrel with CYP3A4-metabolized statins did not demonstrate an increased early risk of adverse cardiovascular events, although a small risk could not be completely excluded.
Blagojevic
Ana
A
Department of Medicine, McGill University Health Center, Quebec, Canada.
Delaney
Joseph A C
JA
Lévesque
Linda E
LE
Dendukuri
Nandini
N
Boivin
Jean-Francois
JF
Brophy
James M
JM
D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D000077144:Clopidogrel; D015331:Cohort Studies; D051544:Cytochrome P-450 CYP3A / Q000502:physiology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D016016:Proportional Hazards Models; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D013988:Ticlopidine