Pharmacodynamic effects of atorvastatin vs. rosuvastatin in coronary artery disease patients with normal platelet reactivity while on dual antiplatelet therapy

Abstract

Background: Levels of platelet reactivity in patients on Dual Antiplatelet Therapy (DAPT) can potentially be influenced by concomitant treatment with statins that inhibit the CYP3A4 system involved in the activation of clopidogrel. Recent studies have shown that a high platelet reactivity during co-administration of clopidogrel and a CYP3A4-metabolized statin (i.e atorvastatin) can be lowered by switching to a non-CYP3A4-metabolized statin (i.e rosuvastatin). Aim of this study was to verify if atorvastatin and rosuvastatin have different pharmacodynamic effects also when they are given to patients with Coronary Artery Disease (CAD) with baseline normal platelet reactivity while on DAPT. Methods: A total of 100 stable CAD patients receiving DPAT (clopidogrel 75 mg plus aspirin 100 mg) who had evidence of normal platelet reactivity after a 1-week statin wash-out period entered the PEARL trial. Patients were randomly assigned to atorvastatin (20 mg day, N=50) or rosuvastatin (10 mg day, N=50) for 30 days. After another 1-week wash-out period to avoid any carryover effect, cross-over was performed, and patients were switched to the other drug which was continued for 30 days. Platelet reactivity (expressed as P2Y (12) reaction units (PRU) by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]) was measured before and at the end of each 30-day treatment period. High platelet reactivity after clopidogrel was defined as a PRU value>208. Results: After the 30-day treatment with atorvastatin, platelet reactivity did not significantly change as compared with baseline, pre-treament evaluation (119±66 vs 136±59 PRU, NS), with 2 patients only showing a PRU>208. Similarly, after 30-day treatment with rosuvastatin, platelet reactivity was unchanged as compared with baseline (135±46 vs 128±62 PRU, NS), with PRU>208 occurring in 3 patients. Conclusion: Atorvastatin does not negatively affect DAPT as compared with rosuvastatin when is given to stable CAD patients with baseline normal platelet reactivity while on DAPT. ClinicalTrials.gov Identifier: [NCT01567774][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01567774&atom=%2Fehj%2F34%2Fsuppl_1%2FP4849.atom