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)

Phase 4

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

• Registration Number: NCT02030054
• Lead Sponsor: University of Roma La Sapienza

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2014-01-06
• Study First Submitted QC: 2014-01-07
• Study First Posted: 2014-01-08
• Status Verified: 2014-12
• Last Update Submitted: 2014-12-03
• Last Update Posted: 2014-12-04
• Study Start: 2015-01
• Primary Completion: 2015-06
• Study Completion: 2015-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Angiographically-proven coronary artery disease;
2. Able to understand and willing to sign the informed CF;
3. Stable clinical condition;
4. treatment with dual antiplatelet therapy (with P2Y12 inhibitors);

Exclusion Criteria

1. Other drugs or medications that affect CYP mediated drug metabolism;
2. Allergy or adverse reactions to administered drugs;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
atorvastatin	Atorvastatin	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.
rosuvastatin	Atorvastatin	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.
atorvastatin	Rosuvastatin	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.
rosuvastatin	Rosuvastatin	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.

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\>208

Trial Locations

Locations (1)

Sapienza Univeristy of Rome; 🇮🇹 Rome, Italy