Pharmacodynamic Effects of Atorvastatin vs. Rosuvastatin on Platelet Reactivity (PEARL)

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

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.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Atorvastatin; Drug: Rosuvastatin

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00161
    • Recruiting
    • Sapienza University
  • Rome, Italy, 00166
    • Not yet recruiting
    • University Sapienza
    • Contact: Francesco Pelliccia, MD; Phone Number: 123 +3906499; Email: f.pelliccia@mclink.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Atorvastatin; Patients will receive randomly atorvastatin (20 mg day) for 30 days	Drug: Atorvastatin; os, 20 mg, once per day, for 30 days; Other Names: Norvasc, Pfizer, USA
ACTIVE_COMPARATOR: Rosuvastatin; Patients will receive randomly rosuvastatin (10 mg per day) for 30 days	Drug: Rosuvastatin; os, 10 mg, once per day, for 30 days; Other Names: Crestor, AstraZeneca, UK

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ANTICIPATED): March 1, 2014
• Study Completion (ANTICIPATED): June 1, 2015

Study Registration Dates

• First Submitted: March 29, 2012
• First Submitted That Met QC Criteria: March 29, 2012
• First Posted (ESTIMATE): March 30, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): May 6, 2013
• Last Update Submitted That Met QC Criteria: May 3, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Coronary artery disease; atorvastatin; rosuvastatin; dual antiplatelet therapy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium
• Other Study ID Numbers: 198/2012/D