Familial Atherosclerosis Treatment Study (FATS)

University of Washington

Status and phase: Completed; Phase 3

Conditions: Myocardial Ischemia; Coronary Arteriosclerosis; Cardiovascular Diseases; Heart Diseases; Coronary Disease

Treatments: Drug: lovastatin; Other: Placebo for colestipol; Drug: colestipol; Other: Placebo for lovastatin; Drug: niacin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00000512

P01HL030086 (U.S. NIH Grant/Contract)

28764-W

Details and patient eligibility

About

To compare the effects of two intensive lipid-lowering regimens with conventional therapy on coronary atherosclerosis as assessed by arteriography.

Full description

BACKGROUND:

For several decades, clinical trials have addressed the question of whether treatment of hyperlipidemia reduces the risk of cardiovascular events. Substantial evidence supports the idea that cardiovascular benefits are related to the degree of reduction in low-density lipoprotein cholesterol level and perhaps to the degree of increase in the high-density lipoprotein cholesterol level. In these trials, changes in lipid levels have usually been small and the overall clinical benefits have been limited. The appearance in the 1980s of more effective treatments for hyperlipidemia, new arteriographic methods for assessing atherosclerosis, and new insights into atherogenesis permitted an objective investigation into whether the progression of atherosclerosis was retarded or reversed by lipid-lowering agents.

The clinical trial was supported by a subproject within a program project grant.

DESIGN NARRATIVE:

Randomized, double-blind, placebo-controlled. Baseline arteriograms were performed and fasting lipid samples drawn before heparinization. Patients were stratified for age below 45 years, cigarette smoking within the previous month, and lipid patterns including familial hypercholesterolemia and triglyceride levels. Patients were given dietary counseling and randomly assigned to one of three treatments: lovastatin (20 mg twice a day) and colestipol (10 g three times a day); niacin (1 g four times a day) and colestipol (10 g three times a day): or conventional therapy with placebo (or colestipol if the LDL cholesterol level was elevated). The primary endpoint was a measure of change in the severity of disease in the proximal coronary arteries as measured by quantitative arteriography.

Enrollment: 146 patients

Sex: Male

Ages: 18 to 62 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Men
• Age 62 or younger
• elevated apolipoprotein B levels
• coronary atherosclerosis
• family history of coronary heart disease.

Exclusion criteria

• diabetes
• severe hypertension
• cancer
• liver disease
• thyroid disease
• kidney disease

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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146 participants in 3 patient groups, including a placebo group

Niacin-Colestipol Group

Experimental group

Description:

Colestipol was begun at a dose of 5 g three times a day with meals and increased to 10 g three times a day after 10 days, unless side effects delayed the increase. Psyllium hydrophic mucilloid (Metamucil) was provided if dietary bran was insufficient to control constipation. Niacin was started at 125 mg twice a day and gradually increased to 500 mg four times a day (with meals and at bedtime) at one month and 1 g four times a day at two months. If the LDL cholesterol level did not fall below 3.1 mmol per liter (120 mg per deciliter) after three months, the dose of niacin was increased to 1.5 g (three tablets) four times a day, but no further.

Treatment:

Drug: niacin

Drug: colestipol

Lovastatin-Colestipol Group

Experimental group

Description:

Colestipol was given as described above. Lovastatin was begun at a dose of 20 mg twice a day (in the morning and at bedtime). If the LDL cholesterol level did not fall below 3.1 mmol per liter after three months, the dose of lovastatin was increased to 40 mg twice a day.

Treatment:

Drug: colestipol

Drug: lovastatin

Conventional-Therapy Group

Placebo Comparator group

Description:

Patients assigned to conventional therapy (the control regimen) received placebos for colestipol and for lovastatin, given as described above, unless their base-line LDL cholesterol level exceeded the 90th percentile for age. We felt obliged to provide such patients (43 percent of the group) with colestipol instead of its placebo. For purposes of blinding, the lovastatin placebo dose for a patient assigned to conventional therapy was doubled each time the lovastatin dose was doubled for a patient assigned to receive lovastatin and colestipol.

Treatment:

Other: Placebo for lovastatin

Drug: colestipol

Other: Placebo for colestipol