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

Phase 3

Completed

Conditions: Atherosclerosis
Cardiovascular Disease

Interventions: Drug: any statin
Drug: Placebo
Drug: niacin

Registration Number: NCT00127218

Lead Sponsor: Johns Hopkins University

Brief Summary: The purpose of this study is to investigate the added benefits of increased high-density lipoprotein (HDL) cholesterol serum levels over and above those achieved by lipid lowering therapy guided by current guidelines, in older individuals with cardiovascular disease.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 145

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	any statin	any statin plus placebo
2	Placebo	any statin plus placebo
1	any statin	any statin plus niacin
1	niacin	any statin plus niacin

Primary Outcome Measures

Name	Time	Method
Changes in Plaque Architecture and Composition Directly Measured by Magnetic Resonance Imaging (MRI) in the Aorta and Carotid Arteries	18 months	The primary endpoint is Changes in plaque architecture and composition directly measured by magnetic resonance imaging (MRI) in the aorta and carotid arteries.

Secondary Outcome Measures

Name	Time	Method
Multiple Combined Events ( Cardiovascular and Cerebrovascular Events as Well as Myocardial Revascularization)	18 months	Cerebrovascular events (newly diagnosed) such as Stroke and Myocardial revascularization (specifically coronary artery bypass grafting, percutaneous coronary interventions, carotid endarterectomy) were recorded