High-Density Lipoprotein (HDL) Cholesterol Increased Plaque Stabilization in the Elderly

The hypothesis being tested is that the current standard lipid lowering therapy, combined
with a 20 percent or greater increase in serum HDL induced by long-acting niacin, reduces
plaque size in older individuals with cardiovascular disease. The specific aims of testing
this hypothesis are:

1. to determine the effects of statin plus placebo vs. statin plus niacin therapy on plaque
size and composition,

2. to determine whether alterations of inflammatory markers of atherosclerosis induced by
lipid lowering therapy parallel alterations of plaque architecture and composition in
older patients with cardiovascular disease,

3. to determine the effects of these interventions on the incidence of cardiovascular and
cerebrovascular events.

The results of the trial will be directly applicable to developing strategies for plaque
stabilization in the elderly who suffer the most from the severe complications of advanced
cardiovascular atherosclerosis.

A total of 144 participants aged 65 and older with cardiovascular or cerebrovascular disease
will be recruited. Participants will be randomized to receive either statin plus niacin or
statin plus a placebo for 18 months. Participants will be provided a prescription for
fluvastatin 80 mg to be taken on a daily basis, or they may continue their ongoing or any
other cholesterol-lowering drugs such as pravastatin 80 mg daily, simvastatin 20 mg daily,
atorvastatin up to 20 mg daily or rosuvastatin up to 20 mg daily. Ten visits are expected,
initially every 4 weeks for dose adjustment. Then visits will be every 6 months; MRI,
Inflammatory Markers tests, and other lab tests will be done at baseline and the visits at
months 6, 12, and 18.

Inclusion Criteria:

- Aged 65 or older

- Documented clinical cardiovascular or cerebrovascular disease due to atherosclerosis

- Candidate for lipid lowering therapy; no contraindication to fluvastatin, niacin or
aspirin therapy

- Low-density lipoprotein (LDL) cholesterol below 150 mg/dl if untreated or below 125
mg/dl on statin monotherapy

- Willing to discontinue present therapy if private physician agrees with enrollment

- Eligible to undergo trans-esophageal magnetic resonance imaging (MRI); no
contraindications to Gadolinium-DTPA, the contrast agent used

- Willing to sign Informed Consent

Exclusion Criteria:

- Ineligibility for MRI procedure due to pacemaker, metal implants, or other
ferromagnetic devices

- Claustrophobia

- Previously documented esophageal disease which would preclude trans-esophageal MRI

- LDL-C greater than 150 mg/dl off lipid lowering therapy or daily statin therapy
requiring doses greater than 20 mg of atorvastatin, 20 mg of simvastatin, 80 mg of
lovastatin, 80 mg of pravastatin, 80 mg of extended release fluvastatin, or 20 mg of
rosuvastatin

- Contraindication or allergy to statins or aspirin

- Current use of or known intolerance or allergy to Niaspan (a long-acting niacin)

- Allergy or intolerance to Gadolinium-DTPA (MRI contrast agent)

- Liver or kidney failure defined clinically and by laboratory data

- Mental, neurologic or social condition preventing understanding of the rationale,
procedures, risks and potential benefits associated with the trial