Abstract W P352: Clopidogrel-Statin Interaction in Secondary Prevention After Ischemic Stroke: A Randomized Double Blind Placebo Controlled Crossover Study
BACKGROUND: In secondary prevention after ischemic stroke variability in individual responsiveness to clopidogrel is a clinically relevant problem. Among possible mechanisms that may contribute to this phenomenon, clopidogrel-statin interactions are discussed. Particularly, competitive metabolization of lipohilic statins (i.e. simvastatin) and clopidogrel by cytochrome P450 (CYP) 3A4 was suggested to reduce the inhibitory effect of clopidogrel on platelet aggregation. In contrast, hydrophilic fluvastatin is predominantly metabolized by CYP 2C9 and is therefore assumed not to alter clopidogrel efficacy. We assessed the hypothesis that simvastatin, in contrast to fluvastatin, reduces clopidogrel-mediated platelet inhibition.
METHODS: We performed a randomized double blind placebo controlled crossover study in 13 patients with acute ischemic stroke. After an initial 13 day period in which all patients received 75 mg clopidogrel/day, one group (n=6) was randomized to additionally receive 20 mg simvastatin/day and placebo for 13 days. During this period the other group (n=7) received 80 mg fluvastatin and placebo in addition to clopidogrel. Regimens were crossed over after a 13 day wash-out period during which patients received clopidogrel only. Switched regimens were then continued for another 13 days. Assessment of ADP-induced platelet aggregation, plasma levels of clopidogrel active metabolite and coagulation was performed at baseline, at each regimen change and at study completion.
RESULTS: We studied 7 female and 6 male patients, ages 63.9±3 years (mean±SD). Plasma levels of clopidogrel active metabolite and platelet aggregation were unaltered when simvastatin or fluvastatin were added to treatment with clopidogrel. Simvastatin decreased prothrombin ratio (decrease from 109±10,5% to 103±11%, p<0,05) when combined with clopidogrel but there was no such change after treatment with fluvastatin and clopidogrel.
CONCLUSIONS: This study indicates that neither fluvastatin nor simvastatin alter clopidogrel-mediated platelet inhibition. In co-administration of simvastatin and clopidogrel we observed decrease in prothrombin ratio which could be due to simvastatin-induced reduction of prothrombin fragment 1 and 2 activity.
Author Disclosures: T. Siepmann: None. D. Heinke: None. J. Kepplinger: None. K. Barlinn: None. V. Puetz: None. G. Gahn: None. U. Bodechtel: None.
- © 2014 by American Heart Association, Inc.