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(Circulation. 2003;107:1568.)
© 2003 American Heart Association, Inc.

Are Antiplatelet Effects of Clopidogrel Inhibited by Atorvastatin?

A Research Question Formulated but Not Yet Adequately Tested

Victor L. Serebruany, MD, PhD; Steven R. Steinhubl, MD; Charles H. Hennekens, MD, DrPH

From the Sinai Thrombosis Center, (V.L.S.), Baltimore, Md; the University of North Carolina (S.R.S.), Chapel Hill, NC; and the University of Miami (C.H.H.), Miami, Fla.

Correspondence to Victor L. Serebruany, MD, Sinai Center for Thrombosis Research, Johns Hopkins University, Sinai Hospital, 2401 West Belvedere Ave, Research Building 209, Baltimore, MD 21215. E-mail heartdrug@aol.com

Key Words: Editorials • platelets • statins • drugs

An extract of the first 250 words of the full text is provided, because this article has no abstract.

With respect to antiplatelet therapy, randomized trials and their meta-analyses¹ indicate benefits of clopidogrel either as an alternative² or an adjunct³ to aspirin in some high-risk patients. Regarding the metabolic pathways of clopidogrel, the active thiol metabolite binds rapidly and irreversibly to platelet adenosine diphosphate (ADP) receptors, thus inhibiting platelet aggregation.⁴ Clopidogrel, a thienopyridine, is a platelet ADP-receptor blocker that is known to be beneficial during and after coronary stenting.^2–5 Clopidogrel is extensively metabolized by the liver. The main circulating metabolite is the carboxylic acid derivative, which has no effect on platelet aggregation. The active metabolite, a thiol derivative, is formed by oxidation of clopidogrel to 2-oxo-clopidogrel and subsequent hydrolysis. Results of in vitro studies in human liver microsomes and recombinant cytochromes P450 have shown that several cytochromes are involved in the oxidative metabolism of clopidogrel.⁶

In randomized trials of secondary and primary prevention of cardiovascular disease and their meta-analyses,⁷ statins reduce risks of myocardial infarction, stroke, and cardiovascular death. Recently, in a randomized trial in patients undergoing percutaneous coronary intervention,⁸ statins have been shown to reduce the incidence of major adverse coronary events, especially among the subgroups of diabetics and those with multivessel disease. In these high-risk patients, the National Cholesterol Education Program III guidelines recommend statin therapy to achieve low-density lipoprotein (LDL) goals of less than 100 mg/dL.⁹ Of the 5 marketed statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin), four (atorvastatin, fluvastatin, lovastatin, and simvastatin) are also metabolized by the cytochrome P450 pathway.¹⁰

Thus, in patients receiving coronary . . . [Full Text of this Article]

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