HDL-Atherosclerosis Treatment Study (HATS)

Study Overview
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Brief Summary
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To measure the effects of lipid-lowering drugs and/or antioxidant vitamins on progression or regression of coronary heart disease as measured by quantitative angiography in patients with low high density lipoprotein (HDL) cholesterol.

Detailed Description
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BACKGROUND: More than one-third of patients with coronary disease have low high density lipoprotein cholesterol (HDLc) levels (less than 35 mg/dl; United States 20th percentile) and normal low density lipoprotein cholesterol (LDLc) (less than 145; United States mean), a group for whom current treatment guidelines are not based on clinical trial data. Low HDLc levels are strong, independent predictors of cardiovascular disease and cardiovascular mortality risk, equally so for both men and women. This high coronary artery disease risk may be due to an imbalance between delivery of cholesterol into the arterial intima by LDL and its removal by HDL. Also, since HDL serve as antioxidants and cytoprotectants, an important HDL role may be to prevent LDL oxidation and thus limit macrophage-mediated intimal lipid accumulation or to prevent vascular cell toxicity. Recent epidemiologic, experimental, and clinical trial evidence suggests that a 15 mg/dl rise in HDL cholesterol would reduce coronary artery disease incidence and mortality by 30 to 70 percent and that antioxidant vitamins E, C, and beta-carotene might reduce coronary artery disease events and atherogenesis. The potential absolute benefit is much greater in those with existing coronary artery disease. It has also been shown that HDLc rises in response to exercise, smoking cessation, weight reduction, and monounsaturated fats. DESIGN NARRATIVE: Randomized, Phase III. Each patient was randomly assigned to a lipid-altering strategy or its placebo and to an antioxidant vitamin strategy or its placebo, in a 2 x 2 factorial design. The four groups were simvastatin-niacin plus an antioxidant vitamin cocktail; simvastatin-niacin plus vitamin placebo; antioxidant vitamins alone plus simvastatin-niacin placebo; or placebos for both strategies. All groups were counseled with respect to diet, exercise, and smoking cessation. The primary endpoint was the average change in proximal obstructive disease during the 2.5 year interval between baseline and the followup study. Secondary endpoints included the frequency of cardiac events, including cardiac death, confirmed non-fatal myocardial infarction, cerebrovascular accident, or revascularization by bypass or angioplasty for medically refractory unstable ischemia. The trial ended in August, 1999.

Conditions
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Cardiovascular Diseases, Coronary Disease, Heart Diseases, Myocardial Ischemia

Intervention / Treatment
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* Drug: simvastatin
* Drug: niacin
* Drug: antioxidants


Participation Criteria
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Eligibility Criteria
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Men and women with low HDL cholesterol, with at least one 50% stenotic coronary lesion or three 30% stenotic coronary lesions. Women range in age from 35 to less than 68 and men from 35 to less than 63.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 68 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: simvastatin|nan|
|Drug: niacin|nan|
|Drug: antioxidants|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |