Brown and colleagues conducted a randomized, controlled, double-blind trial comparing placebo treatment with an antioxidant cocktail (vitamin E, 800IU; vitamin C, 1,000 mg; beta carotene, 25 mg; selenium, 100 mcg), simvastatin, and niacin, or a combination of all three agents in a study population with known coronary heart disease.

The investigators enrolled patients with low-density lipoprotein (LDL) cholesterol levels below 145 mg per dL without medication but depressed high-density lipoprotein (HDL) levels (less than 35 mg per dL). Of the 454 patients who were eligible based on appropriate lipid parameters, 160 were enrolled in the study. Baseline coronary angiography was compared to repeat catheterization after three years of treatment. Lipid levels were followed, and the clinical outcomes were tracked to the occurrence of the first of the following events: nonfatal myocardial infarction, stroke, or revascularization for worsening ischemia.

Patients who received only antioxidants had no significant change in LDL or HDL levels, had angiographic progression of coronary stenoses, and had no significant improvement in clinical outcomes. The group assigned to simvastatin and niacin had LDL reductions averaging 42 percent and HDL increases of 26 percent. Angiographic stenoses regressed slightly in this group, and the incidence of adverse clinical outcomes was significantly reduced (3 percent versus 24 percent for placebo). Patients who had antioxidants added to simvastatin and niacin had less improvement in lipid parameters, progression of coronary stenoses, and loss of the significant reduction in clinical outcomes.

The authors concluded that simvastatin plus niacin improved lipid parameters, angiographic evidence of stenoses, and clinical outcomes in patients with coronary disease and low HDL levels when compared to placebo. The use of antioxidant vitamins had no such effects.