Evaluation of Atorvastatin on Atherosclerosis Composition

Atherosclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00576576
• Other study ID #: IRB00000701
• Secondary ID: GA2580TTEmory #0
• Status: Completed
• Phase: N/A
• First received: December 17, 2007
• Last updated: November 27, 2013
• Start date: July 2007
• Est. completion date: March 2010

Study information

• Verified date: November 2013
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

Drug:
• Atorvastatin
Atorvastatin 80 mg a day

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (3)

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 Ev

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. — View Citation

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 co — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No