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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atorvastatin | Active Comparator | Patients will receive randomly atorvastatin (20 mg day) for 30 days |
|
| Rosuvastatin | Active Comparator | Patients will receive randomly rosuvastatin (10 mg per day) for 30 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin | Drug | os, 20 mg, once per day, for 30 days |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Francesco Pelliccia, MD | Contact | +39064997 | 123 | f.pelliccia@mclink.it |
| Francesco Pelliccia, MD | Contact | +39064997 | 123 |
| Name | Affiliation | Role |
|---|---|---|
| Francesco Pelliccia, MD | University Sapienza | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sapienza University | Recruiting | Rome | 00161 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24444439 | Derived | 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. |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| D017311 | Amlodipine |
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Rosuvastatin | Drug | os, 10 mg, once per day, for 30 days |
|
|
| University Sapienza | Not yet recruiting | Rome | 00166 | Italy |
|
| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |