Clinical trial NCT01567774: Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on Platelet Reactivity
Official title: Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on pLatelet Reactivity in Stable Patients With Coronary Artery Disease Treated With Dual Antiplatelet Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: Coronary artery disease
dual antiplatelet therapy
atorvastatin
rosuvastatin
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2012-03-30
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* Angiographically-proven coronary artery disease
* Class I indication to DAT because of recent (\<12 months) percutaneous coronary intervention and/or recent acute coronary syndrome (\<12 months)
* Stable clinical conditions
* Able to understand and willing to sign the informed CF

Exclusion Criteria:

* Use of other drug interfering with CYP activity such as proton pump inhibitors
* Women of child bearing potential patients must demonstrate a negative pregnancy test performed within 24 hours before CT

Primary outcomes:
measure: Assessment of platelet reaction units
timeFrame: After 30 days of treatment with each drug
Secondary outcomes:
measure: Frequency of high platelet reactivity
timeFrame: After 30 days of treatment with each drug
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Sapienza University
city: Rome
country: Italy
facility: University Sapienza
Study officials:
affiliation: University Sapienza
name: Francesco Pelliccia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.