Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on Platelet Reactivity

Phase 4

• Conditions: Coronary Artery Disease
• Interventions: Drug: Rosuvastatin; Drug: Atorvastatin

• Registration Number: NCT01567774
• Lead Sponsor: University of Roma La Sapienza

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).

Study Timeline

• Study First Submitted: 2012-03-29
• Study First Submitted QC: 2012-03-29
• Study First Posted: 2012-03-30
• Study Start: 2012-04
• Status Verified: 2013-05
• Last Update Submitted: 2013-05-03
• Last Update Posted: 2013-05-06
• Primary Completion: 2014-03
• Study Completion: 2015-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Rosuvastatin	Rosuvastatin	Patients will receive randomly rosuvastatin (10 mg per day) for 30 days
Atorvastatin	Atorvastatin	Patients will receive randomly atorvastatin (20 mg day) for 30 days

Primary Outcome Measures

Name	Time	Method
Assessment of platelet reaction units	After 30 days of treatment with each drug	Absolute changes in platelet reactivity (expressed as P2Y(12) reaction units by the point-of-care VerifyNow assay \[Accumetrics, San Diego, California\])

Secondary Outcome Measures

Name	Time	Method
Frequency of high platelet reactivity	After 30 days of treatment with each drug	Frequency of high platelet reactivity with the 2 study treatments (as defined by a Platelet Reaction Unit value\>240

Trial Locations

Locations (2)

Sapienza University; 🇮🇹 Rome, Italy

University Sapienza; 🇮🇹 Rome, Italy