Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on Platelet Reactivity (PEARL)
Recruitment status was: Recruiting
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on pLatelet Reactivity in Stable Patients With Coronary Artery Disease Treated With Dual Antiplatelet Therapy|
- Assessment of platelet reaction units [ Time Frame: After 30 days of treatment with each drug ] [ Designated as safety issue: No ]Absolute changes in platelet reactivity (expressed as P2Y(12) reaction units by the point-of-care VerifyNow assay [Accumetrics, San Diego, California])
- Frequency of high platelet reactivity [ Time Frame: After 30 days of treatment with each drug ] [ Designated as safety issue: No ]Frequency of high platelet reactivity with the 2 study treatments (as defined by a Platelet Reaction Unit value>240
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Atorvastatin
Patients will receive randomly atorvastatin (20 mg day) for 30 days
os, 20 mg, once per day, for 30 days
Other Name: Norvasc, Pfizer, USA
Active Comparator: Rosuvastatin
Patients will receive randomly rosuvastatin (10 mg per day) for 30 days
os, 10 mg, once per day, for 30 days
Other Name: Crestor, AstraZeneca, UK
At least 1 month after starting DAT (clopidogrel 75 mg and aspirin 100 mg), patients will receive randomly atorvastatin (20 mg day, N=50) or rosuvastatin (10 mg bid, N=50) for 30 days (until T-1).
At this time-point, there will be a wash-out period of 15 days after the first treatment with atorvastatin or rosuvastatin in order to avoid any carry-over effect.
Afterwards, a cross-over will be performed, and patients will be switched to the other drug which will be continued for further 30 days (until T-2).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01567774
|Rome, Italy, 00161|
|Rome, Italy, 00166|
|Principal Investigator:||Francesco Pelliccia, MD||University Sapienza|