Evaluation of Atorvastatin on Atherosclerosis Composition - Full Text View

Purpose

The purpose of this study is to evaluate the effects of Atorvastatin on the coronary atherosclerosis plaque morphology.

Condition	Intervention
Atherosclerosis	Drug: Atorvastatin

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	The Evaluation of Atorvastatin on Wall Shear Stress, Atherosclerosis Composition, and Microvascular Function in Patients With Moderate Coronary Disease

Resource links provided by NLM:

MedlinePlus related topics: Atherosclerosis Coronary Artery Disease

Drug Information available for: Atorvastatin calcium

U.S. FDA Resources

Further study details as provided by Emory University:

Primary Outcome Measures:

Change in necrotic core volume [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in atheroma volume [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Change in Fibrous plaque volume [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	July 2007
Study Completion Date:	March 2010
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A All patients in this arm are given atorvastatin therapy.	Drug: Atorvastatin Atorvastatin 80 mg a day

Detailed Description:

The primary goal of this project is to evaluate the effect of the cholesterol lowering drug Atorvastatin on the composition and character of coronary atherosclerosis (heart blockages). Atorvastatin is known to reduce cholesterol, reduce cardiac events, and halt the progression of coronary atherosclerosis. However, the reduction in cardiac events is out of proportion to the reductions in the total amount of atherosclerosis. Thus, the drug likely decreases cardiac events by changing the composition of the coronary atherosclerotic plaques. It is likely that the drug causes the "heart blockage" to change from a "vulnerable plaque" to a "stable" plaque. There are several features of "vulnerable plaques" that can be detected in arteries of the heart using intravascular ultrasound. The goal of this project is to examine the effects of atorvastatin on atherosclerosis plaque composition using this intravascular ultrasound in patients undergoing serial cardiac catheterizations. Our hypothesis is that atorvastatin will reduce the number of "vulnerable plaques" and increase the number of "stable plaques" seen by intravascular ultrasound. We plan to enroll a total of 20 patients. The patients will be evaluated by cardiac catheterization with intravascular ultrasound analysis and then be treated with atorvastatin for 6 months. These 20 patients will return to the cardiac catheterization laboratory 6 months later for a repeat catheterization with intravascular ultrasound evaluation.

The secondary goal of this proposal is to evaluate in humans the relationship between coronary atherosclerosis (plaque buildup in the arteries of the heart) and wall shear stress (the force generated against the wall of the artery by the flow of blood). The reason for this sub-study is that there is great interest in understanding the characteristics that cause the progression of coronary atherosclerosis. Local forces such as shear stress may play an important role in the focal progression of "vulnerable" atherosclerotic plaques. Indeed, low shear stress is known to be an important factor in the early formation of atherosclerosis. However, the relationship of low shear stress to development and progression of advanced "rupture prone" ("vulnerable") plaques has not been elucidated. Our hypotheses are: (1) "Vulnerable plaques" are more commonly located at areas of low shear stress(2) "Vulnerable plaques" at areas of low shear stress are more likely to progress over the following 6 months than plaques located in normal shear stress regions.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The patients are eligible if they are undergoing catheterization for stable angina or acute coronary syndromes
At the time of catheterization the patient has a "moderate coronary" lesion in the proximal 60mm of an epicardial coronary artery
"Moderate lesion" is defined as a lesion deemed significant enough to warrant further evaluation using CFR and FFR by the treating physician
Patient must have decision making capacity and consented prior to the catheterization
Ages: All ages
Performance Status: all levels

Exclusion Criteria:

1. Screening Exclusion Criteria:

Patients with coronary bypass grafts
Severe valvular heart disease
Patients presenting with a STEMI
Inability to provide informed consent prior to randomization
Creatinine >1.5
Patients who are on a statin with an LDL < 130.
Any patient on a maximum dose of statin (atorvastatin 80mg, simvastatin 80mg, rosuvastatin 20mg, pravastatin 80mg, or fluvastatin 80mg)
Uncontrolled diabetes requiring intensification of therapy
Uncontrolled hypertension requiring the addition of ACEI or ARB

2. Angiographic Ineligibility Criteria:

A Left Main lesion greater than 50% stenosis
The moderate lesion is located beyond 60mm
Collaterals
Coronary Anatomy requiring CABG

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00576576

Locations

United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

Pfizer

Investigators

Principal Investigator:

Habib Samady, MD

Emory University

More Information

Publications:

Kawasaki M, Sano K, Okubo M, Yokoyama H, Ito Y, Murata I, Tsuchiya K, Minatoguchi S, Zhou X, Fujita H, Fujiwara H. Volumetric quantitative analysis of tissue characteristics of coronary plaques after statin therapy using three-dimensional integrated backscatter intravascular ultrasound. J Am Coll Cardiol. 2005 Jun 21;45(12):1946-53.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Eshtehardi P, McDaniel MC, Dhawan SS, Binongo JN, Krishnan SK, Golub L, Corban MT, Raggi P, Quyyumi AA, Samady H. Effect of intensive atorvastatin therapy on coronary atherosclerosis progression, composition, arterial remodeling, and microvascular function. J Invasive Cardiol. 2012 Oct;24(10):522-9.

Samady H, Eshtehardi P, McDaniel MC, Suo J, Dhawan SS, Maynard C, Timmins LH, Quyyumi AA, Giddens DP. Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease. Circulation. 2011 Aug 16;124(7):779-88. Epub 2011 Jul 25.

Responsible Party:	Habib Samady, Emory University Department of Medicine, Section of Cardiology
ClinicalTrials.gov Identifier:	NCT00576576 History of Changes
Other Study ID Numbers:	Emory #07052168, GA2580TT
Study First Received:	December 17, 2007
Last Updated:	September 10, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by Emory University:

Atherosclerosis, vulnerable plaque, IVUS, shear stress

Additional relevant MeSH terms:

Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents

Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013