Evaluate Carotid Artery Plaque Composition by Magnetic Resonance Imaging in People Receiving Cholesterol Medication

Atherosclerosis is a condition in which deposits of fat, cholesterol, and other substances
build up along the inner walls of arteries; these deposits are known as plaque. People with
atherosclerosis are at risk of developing coronary artery disease, in which plaque build-up
occurs in the arteries that supply blood to the heart, and carotid artery disease, in which
plaque build-up occurs in the arteries that deliver blood through the neck to the brain.
These conditions can lead to blood clots, heart attack, and stroke. Research has shown that
people who have more fat content in atherosclerotic plaque may have a higher risk of
experiencing a heart attack or stroke. Treatments for atherosclerosis include lifestyle
changes, medicines, and medical procedures or surgery. There are several medications that can
aid people in controlling their cholesterol levels, including atorvastatin, a medication that
inhibits the production of cholesterol; niacin, a B-complex vitamin that can reduce
cholesterol levels in combination with dietary changes; and colesevelam, a medication that
inhibits fat absorption. Using magnetic resonance imaging (MRI), this study will evaluate
whether these medications, alone or in combination, can decrease the fat content of
atherosclerotic plaques within the carotid arteries of people with coronary artery disease
and carotid artery disease.

This study will enroll people with coronary artery disease or carotid artery disease.
Participants will be randomly assigned to one of the following 40-month treatment groups:

- Group 1 participants will receive atorvastatin, placebo niacin, and placebo colesevelam
each day.

- Group 2 participants will receive atorvastatin, niacin, and placebo colesevelam each
day.

- Group 3 participants will receive atorvastatin, niacin, and colesevelam each day.

At a baseline study visit, participants will undergo a blood collection and will receive
dietary counseling that will focus on lowering cholesterol levels. They will also undergo an
MRI scan of their carotid arteries. For the next 4 months, participants will attend monthly
study visits for repeat blood collection and dietary counseling; for the subsequent 36
months, participants will attend study visits every other month. Repeat carotid artery MRI
scans will occur at Months 12, 24, and 36. At three different times during the study,
researchers will ask participants to record their food consumption for 3 consecutive days.

Inclusion Criteria:

- Clinically established coronary artery disease or carotid artery disease with greater
than 15% stenosis by ultrasound

- Family history of cardiovascular disease

- Apolipoprotein B level greater than or equal to 120 mg/dL (LDL level should be between
100 and 190 mg/dL without medication)

- Has been undergoing lipid therapy for no more than 12 months before study entry

- Medically stable

- Medically able to undergo MRI procedure

Exclusion Criteria:

- Uses pacemaker or has metallic implants

- Has immediate plans for carotid endarterectomy

- History of alcohol or drug abuse

- Active liver disease or liver dysfunction, defined by elevations in alanine
aminotransferase (ALT)/aspartate aminotransferase (AST) levels greater than 1.5 times
the upper limit of normal

- Serum creatine kinase (CK) level greater than 3 times the upper limit of normal before
study entry

- Serum creatinine level greater than 2.5 times the upper limit of normal

- Diabetes, with a fasting glucose level greater than 150 mg/dL or hemoglobin A1c
(HbA1c) level greater than 8% before study entry

- Uncontrolled high blood pressure, defined as average resting systolic blood pressure
greater than 200 mm Hg or average resting diastolic blood pressure greater than 95 mm
Hg