Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on Platelet Reactivity

Summary

Patients with coronary artery disease (CAD) are often treated with dual antiplatelet therapy (DAT), including aspirin and clopidogrel, to prevent from recurrent atherothrombotic events. Levels of platelet reactivity in patients on DAT can be influenced by concomitant treatment with medications that inhibit the CYP3A4 system involved in the activation of clopidogrel. Atorvastatin and simvastatin are metabolized by CYP3A4 \[Clin pharmacokinetic 2002; 41: 343-70\], whereas the cytochrome P450 mediated metabolism of rosuvastatin appears to be minimal and principally mediated by the 2C9 isoenzyme, with little involvement of CYP3A4 \[Clin Ther 2003; 25: 2822-5.\]. Previous studies comparing atorvastatin versus rosuvastatin by means of ex vivo platelet function tests have yielded conflicting results.

Timeline

Start

2012-04

Primary completion

2014-03

Completion

2015-06

Publications

• Pelliccia F, Rosano G, Marazzi G, Vitale C, Spoletini I, Franzoni F, Speziale G, Polacco M, Greco C, Gaudio C. Pharmacodynamic effects of atorvastatin versus rosuvastatin in coronary artery disease patients with normal platelet reactivity while on dual antiplatelet therapy--the PEARL randomized cross-over study. Eur J Pharmacol. 2014 Feb 15;725:18-22. doi: 10.1016/j.ejphar.2014.01.006. Epub 2014 Jan 17.

Drugs

Indications