Familial Atherosclerosis Treatment Study (FATS)
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| ClinicalTrials.gov Identifier: NCT00000512 |
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Recruitment Status :
Completed
First Posted : October 28, 1999
Last Update Posted : December 3, 2015
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cardiovascular Diseases Coronary Arteriosclerosis Coronary Disease Heart Diseases Myocardial Ischemia | Drug: lovastatin Drug: colestipol Drug: niacin Other: Placebo for colestipol Other: Placebo for lovastatin | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 146 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Familial Atherosclerosis Treatment Study |
| Study Start Date : | January 1984 |
| Actual Primary Completion Date : | August 1989 |
| Actual Study Completion Date : | August 1989 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Niacin—Colestipol Group
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.
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Drug: colestipol
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.
Other Name: Colestid Drug: niacin 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.
Other Name: nicotinic acid |
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Experimental: Lovastatin—Colestipol Group
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.
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Drug: lovastatin
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.
Other Name: Mevacor Drug: colestipol 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.
Other Name: Colestid |
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Placebo Comparator: Conventional-Therapy Group
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.
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Drug: colestipol
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.
Other Name: Colestid Other: Placebo for colestipol Placebo for colestipol. Other: Placebo for lovastatin Placebo for lovastatin |
- Change in the Mean Severity of Proximal Stenosis [ Time Frame: Baseline and 2.5 years of therapy. ]At base line, the average percentage of stenosis caused by the worst lesion in each of nine proximal segments was 34 percent. On average, after 2 1/2 years of conventional therapy, this index of stenosis increased by 2.1 percentage points. By contrast, it decreased by 0.7 point during treatment with lovastatin and colestipol and by 0.9 with niacin and colestipol (P for trend <0.003). Thus, at the end of the study, on average, these nine lesions were almost 3 percentage points less severe among patients treated intensively rather than conventionally. This difference represents almost 1/10 of the amount of disease present at base line (34 percent stenosis). The minimum diameter, an alternative index of the severity of disease, in the nine proximal lesions averaged 1.91 mm for all patients. It decreased (worsened) by 0.050 mm with conventional therapy but increased (improved) by 0.012 mm with lovastatin and colestipol and by 0.035 with niacin and colestipol (P for trend <0.01).
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| Ages Eligible for Study: | 18 Years to 62 Years (Adult) |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00000512
| Principal Investigator: | B. Greg Brown, M.D., Ph.D | University of Washington |
Publications:
| Responsible Party: | Xue-Qiao Zhao, Research Professor of Medicine, University of Washington |
| ClinicalTrials.gov Identifier: | NCT00000512 |
| Other Study ID Numbers: |
28764-W P01HL030086 ( U.S. NIH Grant/Contract ) |
| First Posted: | October 28, 1999 Key Record Dates |
| Last Update Posted: | December 3, 2015 |
| Last Verified: | December 2015 |
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Heart Diseases Atherosclerosis Coronary Disease Coronary Artery Disease Myocardial Ischemia Arteriosclerosis Ischemia Cardiovascular Diseases Pathologic Processes Arterial Occlusive Diseases Vascular Diseases Niacin Niacinamide Nicotinic Acids Lovastatin |
L 647318 Dihydromevinolin Colestipol Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Vasodilator Agents Vitamin B Complex Vitamins Micronutrients Nutrients Growth Substances Physiological Effects of Drugs Anticholesteremic Agents |