HDL-Atherosclerosis Treatment Study (HATS)
Condition: Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Ischemia
MeSH terms: Cardiovascular Diseases; Heart Diseases; Coronary Disease; Myocardial Ischemia; Ischemia
Study type: Interventional
Phase: Phase 3

Summary: 
      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: 
      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.
    

Intervention name(s): simvastatin; niacin; antioxidants
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Niacin; Simvastatin; Antioxidants
Allocation: Randomized
Intervention model: Factorial Assignment
Primary purpose: Prevention