Clopidogrel Atorvastatin

Lau WC, Carville DG, Bates ER. Clinical significance of the atorvastatin-clopidogrel drug-drug interaction. Circulation 2004 I I0 e66-e67 author reply e66-e67. 

CNNa 143-33-9) see Alclofenac Alpidem Amphetaminil Atorvastatin calcium Azatadine Calcium pantothenate Carnitine Clopidogrel hydrogensulfate Clortermine Dexrazoxane Diclofenac Diloxanide Edetic acid Epinastine hydrochloride Ethosuximide Ethotoin Fenoprofen Ibuprofen Irbesartan Ketoprofen Lonazolac Mephenytoin Mepindolol Montelukast sodium Nabilone Oxymetazoline Paramethadione Pentorex Saquinavir Suprofen Thiamphenicol Tolmetin Trimazosin Zolpidem sodium cyanoborohydride... 

In 45 patients with acute coronary syndrome randomized to receive either atorvastatin 10 mg/day or pravastatin 40 mg/day neither atorvastatin nor pravastatin significantly affected clopidogrel-induced inhibition of platelet activation nor did clopidogrel affect the therapeutic efficacy of atorvastatin (84). 

The inhibitory potency of clopidogrel on ADP-induced platelet activation was not attenuated when it was coadministered with atorvastatin (20 mg/day) for 5 weeks in 51 patients with acute coronary syndromes (86). Atorvastatin had no effect on either clopidogrel-induced inhibition of platelet aggregation initiated by ADP 5 or 10 pmol/l or clopidogrel-induced reduction of the membrane expression of P-selectin and CD40L induced by ADP. 

Lau WC. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation a new drug-drug interaction. Circulation 2003 107 32-7. 

Saw J. Lack of adverse clopidogrel-atorvastatin clinical interaction from secondary analysis of a randomized, placebo-controlled clopidogrel trial. Circulation 2003 108 921 1. 

Serebruany VL. Are antiplatelet effects of clopidogrel inhibited by atorvastatin A research question formulated but not yet adequately tested. Circulation 2003 107 1568-9. 

Mitsios JV, Papathanasiou AI, Rodis FI, Elisaf M, Goudevenos JA, Tselepis AD. Atorvastatin does not affect the antiplatelet potency of clopidogrel when it is administered concomitantly for 5 weeks in patients with acute coronary syndromes. Circulation 2004 109(ll) 1335-8. 

Serebruany VL, Midei MG, Malinin AI, Oshrine BR, Lowry DR, Sane DC, Tanguay JF, Steinhubl SR, Berger PB, O Connor CM, Hennekens CH. Absence of interaction between atorvastatin or other statins and clopidogrel results from the interaction study. Arch Intern Med 2004 164(18) 2051-7. 

Wienbergen H, Gift AK, Schiele R, et al. MITRA PLUS Study Group. Comparison of clinical benefits of clopidogrel therapy in patients with acute coronary syndromes taking atorvastatin versus other statin therapies. Am J Cardiol 2003 92 285-288. 

Gorchakova O, von Beckerath N, Gawaz M, et al. Antiplatelet effects of a 600 mg loading dose of clopidogrel are not attenuated in patients receiving atorvastatin or simvastatin for at least 4 weeks prior to coronary artery stenting. Eur Heart J 2004 25 1898-1902. 

Clopidogrel is converted to an active thiol metabolite by several CYP isoforms, including 3A4 this then binds rapidly and irreversibly with platelet adenosine diphosphate receptors, thus inhibiting platelet aggregation, At present, inhibition of the antiplatelet effects of clopidogrel by atorvastatin represents a formulated but untested hypothesis, and these agents maybe administered concurrently. 

STATINS ANTIPLATELET AGENTS -CLOPIDOGREL Atorvastatin and possibly simvastatin 1 the antiplatelet effect of dopidogrel in a dose-dependent manner Atorvastatin and simvastatin inhibit CYP3A4-mediated activation of dopidogrel Use these statins at the lowest possible dose otherwise consider using an alternative statin... 

Clarke, T.A. and Waskell, L.A. (2003) The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin. Drug Metabolism and Disposition The Biological Fate of Chemicals, 31, 53-59. 

Some evidence suggests that atorvastatin, and possibly other CYP3A4-metabolised statins (e.g. simvastatin) may interfere with the antiplatelet actions of clopidogrel, but the data is conflicting and there is currently insufficient evidence to warrant changing practice. 

Dose may be an important factor as to whether or not a significant clinical interaction occurs. One study found that a high loading dose of clopidogrel (600 mg) was not affected by statins, but there is increased risk of serious bleeding with this dose. Lower doses of statins (e.g. atorvastatin 10 mg daily) also appear to be less likely to interact, and one study found that the effect was dose-dependent. ... 

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