Evaluation of Atorvastatin on Atherosclerosis Composition

The Evaluation of Atorvastatin on Wall Shear Stress, Atherosclerosis Composition, and Microvascular Function in Patients With Moderate Coronary Disease

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

Study Overview

• Status: Completed
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: Atorvastatin

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

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:

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

Exclusion Criteria:

1. Screening Exclusion Criteria:

1. Patients with coronary bypass grafts
2. Severe valvular heart disease
3. Patients presenting with a ST segment elevation myocardial infarction (STEMI)
4. Inability to provide informed consent prior to randomization
5. Creatinine >1.5
6. Patients who are on a statin with an LDL < 130.
7. Any patient on a maximum dose of statin (atorvastatin 80mg, simvastatin 80mg, rosuvastatin 20mg, pravastatin 80mg, or fluvastatin 80mg)
8. Uncontrolled diabetes requiring intensification of therapy
9. Uncontrolled hypertension requiring the addition of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker

2. Angiographic Ineligibility Criteria:

1. A Left Main lesion greater than 50% stenosis
2. The moderate lesion is located beyond 60mm
3. Collaterals
4. Coronary Anatomy requiring coronary artery bypass grafting (CABG)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; All patients in this arm are given atorvastatin therapy.	Drug: Atorvastatin; Atorvastatin 80 mg a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Necrotic Core Volume	Virtual Histology-Intravascular Ultrasound (VH-IVUS) defined necrotic core cross sectional area (CSA) measured in each VH-IVUS frame and averaged over length of studied vessel at baseline and follow -up. Change in necrotic core CSA between baseline and follow-up was calculated (subtracting the baseline value from the follow-up value).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Atheroma Volume	Change in atheroma volume between baseline and follow-up is reported. This was derived by subtracting the baseline value from the 6-month value.	6 months
Change in Fibrous Plaque Volume	Change in fibrous plaque volume between baseline and follow-up. This was derived by subtracting the baseline value from the 6-month value.	6 months

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Pfizer
• Investigators: Principal Investigator: Habib Samady, MD, Emory University

Publications and helpful links

General 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. doi: 10.1016/j.jacc.2004.09.081.
• 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. doi: 10.1161/CIRCULATIONAHA.111.021824. Epub 2011 Jul 25.
• Eshtehardi P, McDaniel MC, Suo J, Dhawan SS, Avati Nanjundappa RP, Sawaya FJ, King AR, Oshinski JN, Taylor WR, Quyyumi AA, Giddens DP, Samady H. Coronary Plaque Progression Occurs Distal to Stenoses in Segments with Low Wall Shear Stress: A Prospective Evaluation in Patients with Coronary Artery Disease. Arterioscler Thromb Vasc Biol 2010;30(11);e251.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: December 17, 2007
• First Submitted That Met QC Criteria: December 18, 2007
• First Posted (Estimate): December 19, 2007

Study Record Updates

• Last Update Posted (Estimate): December 24, 2013
• Last Update Submitted That Met QC Criteria: November 27, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Atherosclerosis, vulnerable plaque, IVUS, shear stress
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: IRB00000701; GA2580TT (Other Identifier: Other); Emory #07052168 (Other Identifier: Other)