Carotid Plaque Characteristics by MRI in AIM-HIGH (Carotid MRI Substudy)

Completed

• Conditions: Coronary Artery Disease; Carotid Artery Diseases; Atherosclerosis
• Interventions: Drug: Simvastatin, simvastatin plus extended-release niacin

• Registration Number: NCT01178320
• Lead Sponsor: University of Washington

Brief Summary

Heart attacks and strokes caused by the unstable atherosclerotic plaques remain the leading cause of death in the United States. Unstable plaques often have more fat than stable plaques. This study will investigate if a treatment with LDL-lowering plus HDL-raising compared with LDL-lowering alone would more effectively reduce the plaque fat content assessed by magnetic resonance imaging (MRI), therefore, further reducing heart attacks and strokes.

Detailed Description

Although studies have suggested that plaque morphology and composition are important determinants of plaque stability, our understanding on plaque tissue components is mainly from histological studies until recent development in MRI technique. A low level of HDL is associated with higher risk of cardiovascular events and increased amount of lipid content in the carotid plaques. Treatment with LDL-lowering plus HDL-raising compared with LDL-lowering alone more effectively protects against atherosclerosis progression. It is widely believed that HDL or its apolipoproteins mediate the removal of excess free cholesterol from peripheral cells and the cholesterol is delivered via either LDL or HDL to the liver for excretion into the bile. However, it has not been tested and approved in human atherosclerotic condition in vivo. The NIH/Abbott-funded multi-center AIM-HIGH trial is designed to compare the clinical efficacy of LDL-lowering alone with statin versus LDL-lowering plus HDL-raising with statin plus nicotinic acid combination therapy in patients with established vascular disease and high triglycerides and low HDL.

We propose to conduct a carotid MRI sub-study in 220 subjects enrolled in AIM-HIGH to investigate the important vascular biological mechanisms of HDL-raising therapy. Image collection will occur at 3 timepoints. The hypotheses and specific aims are:

* (1) To test the primary hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the mean plaque lipid composition in carotid arteries assessed by MRI.

* (2) To test the hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the plaque burden including volume and wall thickness.

* (3) To test the hypothesis that increased plaque lipid composition or vessel wall thickness by MRI is associated with increased risk of cardiovascular events.

* (4)To test a hypothesis that LDL-lowering plus HDL-raising, compared to LDL-lowering alone, will promote more rapid plaque lipid depletion. And determine the time-course of atherosclerotic plaque lipid depletion during lipid therapy.

* (5) To examine the association of clinical risk factors, lipids, lipoprotein heterogeneity, inflammatory markers and carotid plaque characteristics.

This MRI sub-study offers a unique opportunity to investigate the effectiveness of LDL-lowering plus HDL-raising therapy on human atherosclerotic plaque in vivo, to examine the association of plaque characteristics both lipid composition and volume assessed by MRI and cardiovascular outcome, and to gain novel insights in our understanding of atherosclerotic plaque pathology and the mechanisms of intensive lipid management in preventing cardiovascular events.

Study Timeline

• Study Start: 2008-03
• Study First Submitted: 2010-08-05
• Study First Submitted QC: 2010-08-06
• Study First Posted: 2010-08-10
• Primary Completion: 2013-04
• Study Completion: 2015-02
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-07
• Last Update Posted: 2018-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 230

Inclusion Criteria

• Eligible for main AIM-HIGH study (NCT00120289)
• Medically able to undergo MRI procedure
• Willing to provide informed consent for participation in this substudy

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Exclusion Criteria

• Uses pacemaker or has metallic implants
• History of bilateral carotid endarterectomy
• Glomerular filtration rate less than 60 mL/min/1.73 m^2

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Simvastatin	Simvastatin, simvastatin plus extended-release niacin	Participants in the main AIM-HIGH study who are receiving simvastatin.
Simvastatin and Extended-Release Niacin	Simvastatin, simvastatin plus extended-release niacin	Participants in the main AIM-HIGH study who are receiving simvastatin and extended-release niacin.

Primary Outcome Measures

Name	Time	Method
Mean plaque lipid composition in carotid arteries assessed by MR	Through 24Months post AIM-HIGH Randomization	To test the primary hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the mean plaque lipid composition in carotid arteries assessed by MRI.

Secondary Outcome Measures

Name	Time	Method
Additional plaque characteristics as assessed by MRI	Through 24Months post AIM-HIGH Randomization	To test the additional hypotheses regarding plaque burden, plaque lipid depletion time course, association with cardiovascular event risk and lipid characteristics.

Trial Locations

Locations (19)

Long Beach VA Medical Center; 🇺🇸 Long Beach, California, United States

Cardiovascular Consultants; 🇺🇸 Phoenix, Arizona, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Philadelphia VA Medical Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Kelsey Research Foundation; 🇺🇸 Houston, Texas, United States

Methodist Hospital; 🇺🇸 Houston, Texas, United States

Heart Health Institute; 🇨🇦 Calgary, Alberta, Canada

Puget Sound VA Medical Center, Seattle Campus; 🇺🇸 Seattle, Washington, United States

University of Western Ontario; 🇨🇦 London, Ontario, Canada

Harborview Medical Center; 🇺🇸 Seattle, Washington, United States

University of Calgary; 🇨🇦 Calgary, Alberta, Canada

Wake Forest University; 🇺🇸 Winston-Salem, North Carolina, United States

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

University of Washington; 🇺🇸 Seattle, Washington, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States