Evaluation of Atorvastatin on Atherosclerosis Composition

Not Applicable

Completed

• Conditions: Atherosclerosis
• Interventions: Drug: Atorvastatin

• Registration Number: NCT00576576
• Lead Sponsor: Emory University

Brief Summary

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

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 Timeline

• Study Start: 2007-07
• Study First Submitted: 2007-12-17
• Study First Submitted QC: 2007-12-18
• Study First Posted: 2007-12-19
• Primary Completion: 2010-03
• Study Completion: 2010-03
• Results First Submitted: 2012-11-28
• Results First Submitted QC: 2013-08-13
• Results First Posted: 2013-10-18
• Status Verified: 2013-11
• Last Update Submitted: 2013-11-27
• Last Update Posted: 2013-12-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

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:

2. Patients with coronary bypass grafts

3. Severe valvular heart disease

4. Patients presenting with a ST segment elevation myocardial infarction (STEMI)

5. Inability to provide informed consent prior to randomization

6. Creatinine >1.5

7. Patients who are on a statin with an LDL < 130.

8. Any patient on a maximum dose of statin (atorvastatin 80mg, simvastatin 80mg, rosuvastatin 20mg, pravastatin 80mg, or fluvastatin 80mg)

9. Uncontrolled diabetes requiring intensification of therapy

10. Uncontrolled hypertension requiring the addition of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker

11. Angiographic Ineligibility Criteria:

12. A Left Main lesion greater than 50% stenosis

13. The moderate lesion is located beyond 60mm

14. Collaterals

15. Coronary Anatomy requiring coronary artery bypass grafting (CABG)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
A	Atorvastatin	All patients in this arm are given atorvastatin therapy.

Primary Outcome Measures

Name	Time	Method
Change in Necrotic Core Volume	6 months	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).

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States