Evaluation of Atorvastatin on Atherosclerosis Composition

Study Overview
=================
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.

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

Conditions
-----------------
Atherosclerosis

Intervention / Treatment
-----------------
* Drug: Atorvastatin


Participation Criteria
=================
Eligibility 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 coronary flow reserve (CFR) and fractional flow reserve (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 ST segment elevation myocardial infarction (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 angiotensin-converting enzyme inhibitor or angiotensin receptor blocker 2. Angiographic Ineligibility Criteria: A Left Main lesion greater than 50% stenosis The moderate lesion is located beyond 60mm Collaterals Coronary Anatomy requiring coronary artery bypass grafting (CABG)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>All patients in this arm are given atorvastatin therapy. | Drug: Atorvastatin<br>* Atorvastatin 80 mg a day<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Atherosclerosis, vulnerable plaque, IVUS, shear stress