Pharmacokinetic interactions between clopidogrel and rosuvastatin: Effects on vascular protection in subjects with coronary heart disease

Significant decrease in outcomes with statins administration in the first 24 h of an acute myocardial infarction [1–4] and reduction of myocardial injury markers after high-dose statin given few hours before percutaneous interventions [5,6] were observed. These effects of statins take place before lipid changes [7,8]. Clopidogrel, a pro-drug largely prescribed for patients undergoing stent implantation, is metabolized in the liver via cytochrome P450 (CYP2C19 and CYP3A4) to form an active metabolite that inhibits the P2Y(12) ADP platelet receptor [9,10]. Rosuvastatin is partially metabolized by CYP2C9 and CYP2C19 [11]. Functional and anatomical changes of the endothelium, an inflammatory substrate and coagulation activation participate on the pathophysiology of acute coronary syndromes [12,13]. New biomarkers, such as endothelial and platelet microparticles (EMP and PMP), endothelial progenitor cells (EPC), platelet function tests and endothelial-dependent flow-mediated dilation (FMD) have been proposed for the evaluation of vascular homeostasis [14,15]. Thus, we