Familial Atherosclerosis Treatment Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 146
- 主要终点
- Change in the Mean Severity of Proximal Stenosis
研究概览
简要总结
To compare the effects of two intensive lipid-lowering regimens with conventional therapy on coronary atherosclerosis as assessed by arteriography.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 62 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Age 62 or younger
- •elevated apolipoprotein B levels
- •coronary atherosclerosis
- •family history of coronary heart disease.
排除标准
- •severe hypertension
- •liver disease
- •thyroid disease
- •kidney disease
研究组 & 干预措施
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.
干预措施: colestipol (Drug)
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.
干预措施: niacin (Drug)
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.
干预措施: lovastatin (Drug)
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.
干预措施: colestipol (Drug)
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.
干预措施: colestipol (Drug)
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.
干预措施: Placebo for colestipol (Other)
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.
干预措施: Placebo for lovastatin (Other)
结局指标
主要结局
Change in the Mean Severity of Proximal Stenosis
时间窗: 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).
次要结局
未报告次要终点
研究者
Xue-Qiao Zhao
Research Professor of Medicine
University of Washington