Are Antiplatelet Effects of Clopidogrel Inhibited by Atorvastatin? A Research Question Formulated but Not Yet Adequately Tested

Abstract

With respect to antiplatelet therapy, randomizedtrials and their meta-analyses1 indicate benefits ofclopidogrel 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 Clopi-dogrel, 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 o

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