Evaluation of Atorvastatin on Atherosclerosis Composition

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Habib Samady, Emory University
ClinicalTrials.gov Identifier:
NCT00576576
First received: December 17, 2007
Last updated: November 27, 2013
Last verified: November 2013
  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: 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:


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 ]
    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:
  • Change in Atheroma Volume [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change in fibrous plaque volume between baseline and follow-up. This was derived by subtracting the baseline value from the 6-month value.


Enrollment: 27
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:

  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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Habib Samady, MD, Emory University
ClinicalTrials.gov Identifier: NCT00576576     History of Changes
Other Study ID Numbers: IRB00000701, GA2580TT, Emory #07052168
Study First Received: December 17, 2007
Results First Received: November 28, 2012
Last Updated: November 27, 2013
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
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014