Pharmacodynamic Comparison of Rosuvastatin Versus Atorvastatin on Platelet Reactivity in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy With New P2Y12 Inhibitors (Trial gRANADa)

Study Overview
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Brief Summary
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Statin interference has been suggested among the mechanisms of reduction of the antiplatelet effect of clopidogrel. The purpose of this study is to evaluate pharmacodynamic effects of rosuvastatin and atorvastatin on platelet reactivity in patients with coronary artery disease undergone double antiplatelet therapy with new P2Y12 inhibitors. This is a single-center, prospective, randomized, crossover study conducted in the Department of Heart and Great Vessels Attilio Reale, Sapienza University, Rome, Italy. All consecutive patients undergone PTCA in our institution in the period between July 2013 and December 2013 will be eligible to be enrolled. Patients will be offered to participate to the trial at time of 1-month post-angioplasty follow-up visit.patients receiving dual antiplatelet therapy (prasugrel 10 mg or brilique 90 mg x 2 plus aspirin 100 mg) after percutaneous coronary intervention. Patients were randomly assigned to rosuvastatin (20 mg day) or atorvastatin (40 mg day) for 30 days. After 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 function will be evaluated using a validated method: the VerifyNow System (Accumetrics Inc., San Diego, CA), which is a point-of-care turbidimetry-based optical detection system that measures platelet-induced aggregation. Platelet function will be measured with the VerifyNow P2Y12 test at baseline and after 30 days from rosuvastatin or atorvastatin administration. Platelet reactivity will be expressed in P2Y12 reaction units (PRU). PRU values >208 are suggestive of high platelet reactivity.

Detailed Description
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Statin interference has been suggested among the mechanisms of reduction of the antiplatelet effect of clopidogrel. The purpose of this study is to evaluate pharmacodynamic effects of rosuvastatin and atorvastatin on platelet reactivity in patients with coronary artery disease undergone double antiplatelet therapy with new P2Y12 inhibitors. This is a single-center, prospective, randomized, crossover study conducted in the Department of Heart and Great Vessels Attilio Reale, Sapienza University, Rome, Italy.

Official Title
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Pharmacodynamic Comparison of Rosuvastatin Versus Atorvastatin on Platelet Reactivity in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy With New P2Y12 Inhibitors

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; Able to understand and willing to sign the informed CF; Stable clinical condition; treatment with dual antiplatelet therapy (with P2Y12 inhibitors); Exclusion Criteria: Other drugs or medications that affect CYP mediated drug metabolism; Allergy or adverse reactions to administered drugs;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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 were randomly assigned to atorvastatin (40 mg day) or rosuvastatin (20 mg day) for 30 days. After 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. | Drug: Atorvastatin<br>* Patients were randomly assigned to atorvastatin (40 mg day) for 30 days. After 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.<br>* Other names: torvast, totalip;Drug: Rosuvastatin<br>* Patients were randomly assigned to rosuvastatin (20 mg day) for 30 days. After 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.<br>* Other names: crestor, provisacor,;|
| Active Comparator: rosuvastatin<br>Patients were randomly assigned to atorvastatin (40 mg day) or rosuvastatin(20 mg day) for 30 days. After 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. | Drug: Atorvastatin<br>* Patients were randomly assigned to atorvastatin (40 mg day) for 30 days. After 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.<br>* Other names: torvast, totalip;Drug: Rosuvastatin<br>* Patients were randomly assigned to rosuvastatin (20 mg day) for 30 days. After 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.<br>* Other names: crestor, provisacor,;|

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>208 | After 30 days of treatment with each drug |