Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on Platelet Reactivity

Study Overview
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Brief Summary
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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
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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).

Official Title
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Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on pLatelet Reactivity in Stable Patients With Coronary Artery Disease Treated With Dual Antiplatelet Therapy

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atorvastatin<br>Patients will receive randomly atorvastatin (20 mg day) for 30 days | Drug: Atorvastatin<br>* os, 20 mg, once per day, for 30 days<br>* Other names: Norvasc, Pfizer, USA;|
| Active Comparator: Rosuvastatin<br>Patients will receive randomly rosuvastatin (10 mg per day) for 30 days | Drug: Rosuvastatin<br>* os, 10 mg, once per day, for 30 days<br>* Other names: Crestor, AstraZeneca, UK;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of high platelet reactivity | Frequency of high platelet reactivity with the 2 study treatments (as defined by a Platelet Reaction Unit value>240 | After 30 days of treatment with each drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary artery disease, dual antiplatelet therapy, atorvastatin, rosuvastatin