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Familial Atherosclerosis Treatment Study (FATS)

Primary Purpose

Cardiovascular Diseases, Coronary Arteriosclerosis, Coronary Disease

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
lovastatin
colestipol
niacin
Placebo for colestipol
Placebo for lovastatin
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiovascular Diseases

Eligibility Criteria

18 Years - 62 Years (Adult)MaleDoes not accept 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Niacin-Colestipol Group

    Lovastatin-Colestipol Group

    Conventional-Therapy Group

    Arm 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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Change in the Mean Severity of Proximal Stenosis
    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).

    Secondary Outcome Measures

    Full Information

    First Posted
    October 27, 1999
    Last Updated
    December 1, 2015
    Sponsor
    University of Washington
    Collaborators
    National Heart, Lung, and Blood Institute (NHLBI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00000512
    Brief Title
    Familial Atherosclerosis Treatment Study
    Acronym
    FATS
    Official Title
    Familial Atherosclerosis Treatment Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    January 1984 (undefined)
    Primary Completion Date
    August 1989 (Actual)
    Study Completion Date
    August 1989 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Washington
    Collaborators
    National Heart, Lung, and Blood Institute (NHLBI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cardiovascular Diseases, Coronary Arteriosclerosis, Coronary Disease, Heart Diseases, Myocardial Ischemia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    146 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Niacin-Colestipol Group
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    Lovastatin-Colestipol Group
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    Conventional-Therapy Group
    Arm Type
    Placebo Comparator
    Arm 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.
    Intervention Type
    Drug
    Intervention Name(s)
    lovastatin
    Other Intervention Name(s)
    Mevacor
    Intervention Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    colestipol
    Other Intervention Name(s)
    Colestid
    Intervention 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.
    Intervention Type
    Drug
    Intervention Name(s)
    niacin
    Other Intervention Name(s)
    nicotinic acid
    Intervention Description
    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.
    Intervention Type
    Other
    Intervention Name(s)
    Placebo for colestipol
    Intervention Description
    Placebo for colestipol.
    Intervention Type
    Other
    Intervention Name(s)
    Placebo for lovastatin
    Intervention Description
    Placebo for lovastatin
    Primary Outcome Measure Information:
    Title
    Change in the Mean Severity of Proximal Stenosis
    Description
    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).
    Time Frame
    Baseline and 2.5 years of therapy.

    10. Eligibility

    Sex
    Male
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    62 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    B. Greg Brown, M.D., Ph.D
    Organizational Affiliation
    University of Washington
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    2215615
    Citation
    Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, Zhao XQ, Bisson BD, Fitzpatrick VF, Dodge HT. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990 Nov 8;323(19):1289-98. doi: 10.1056/NEJM199011083231901.
    Results Reference
    background
    PubMed Identifier
    8252687
    Citation
    Zhao XQ, Brown BG, Hillger L, Sacco D, Bisson B, Fisher L, Albers JJ. Effects of intensive lipid-lowering therapy on the coronary arteries of asymptomatic subjects with elevated apolipoprotein B. Circulation. 1993 Dec;88(6):2744-53. doi: 10.1161/01.cir.88.6.2744.
    Results Reference
    background
    PubMed Identifier
    8106695
    Citation
    Stewart BF, Brown BG, Zhao XQ, Hillger LA, Sniderman AD, Dowdy A, Fisher LD, Albers JJ. Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein cholesterol. J Am Coll Cardiol. 1994 Mar 15;23(4):899-906. doi: 10.1016/0735-1097(94)90635-1.
    Results Reference
    background
    PubMed Identifier
    7695184
    Citation
    Brown BG, Hillger L, Zhao XQ, Poulin D, Albers JJ. Types of change in coronary stenosis severity and their relative importance in overall progression and regression of coronary disease. Observations from the FATS Trial. Familial Atherosclerosis Treatment Study. Ann N Y Acad Sci. 1995 Jan 17;748:407-17; discussion 417-8. doi: 10.1111/j.1749-6632.1994.tb17337.x. No abstract available.
    Results Reference
    background
    PubMed Identifier
    7500507
    Citation
    Maher VM, Brown BG, Marcovina SM, Hillger LA, Zhao XQ, Albers JJ. Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a). JAMA. 1995 Dec 13;274(22):1771-4.
    Results Reference
    background
    PubMed Identifier
    10208998
    Citation
    Zambon A, Hokanson JE, Brown BG, Brunzell JD. Evidence for a new pathophysiological mechanism for coronary artery disease regression: hepatic lipase-mediated changes in LDL density. Circulation. 1999 Apr 20;99(15):1959-64. doi: 10.1161/01.cir.99.15.1959.
    Results Reference
    background

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