Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease

N Engl J Med. 2001 Nov 29;345(22):1583-92. doi: 10.1056/NEJMoa011090.

Abstract

Background: Both lipid-modifying therapy and antioxidant vitamins are thought to have benefit in patients with coronary disease. We studied simvastatin-niacin and antioxidant-vitamin therapy, alone and together, for cardiovascular protection in patients with coronary disease and low plasma levels of HDL.

Methods: In a three-year, double-blind trial, 160 patients with coronary disease, low HDL cholesterol levels and normal LDL cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, vitamins, simvastatin-niacin plus antioxidants; or placebos. The end points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization).

Results: The mean levels of LDL and HDL cholesterol were unaltered in the antioxidant group and the placebo group; these levels changed substantially (by -42 percent and +26 percent, respectively) in the simvastatin-niacin group. The protective increase in HDL2 with simvastatin plus niacin was attenuated by concurrent therapy with antioxidants. The average stenosis progressed by 3.9 percent with placebos, 1.8 percent with antioxidants (P=0.16 for the comparison with the placebo group), and 0.7 percent with simvastatin-niacin plus antioxidants (P=0.004) and regressed by 0.4 percent with simvastatin-niacin alone (P<0.001). The frequency of the clinical end point was 24 percent with placebos; 3 percent with simvastatin-niacin alone; 21 percent in the antioxidant-therapy group; and 14 percent in the simvastatin-niacin-plus-antioxidants group.

Conclusions: Simvastatin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels. The use of antioxidant vitamins in this setting must be questioned.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antioxidants / therapeutic use*
  • Apolipoproteins / blood
  • Ascorbic Acid / blood
  • Ascorbic Acid / therapeutic use
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control
  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood
  • Coronary Angiography
  • Coronary Disease / drug therapy
  • Coronary Disease / mortality
  • Coronary Disease / prevention & control*
  • Coronary Stenosis / drug therapy*
  • Double-Blind Method
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use*
  • Lipids / blood
  • Male
  • Middle Aged
  • Niacin / adverse effects
  • Niacin / therapeutic use*
  • Selenium / therapeutic use
  • Simvastatin / therapeutic use*
  • Vitamin E / blood
  • alpha-Tocopherol / therapeutic use
  • beta Carotene / blood
  • beta Carotene / therapeutic use

Substances

  • Antioxidants
  • Apolipoproteins
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Lipids
  • beta Carotene
  • Vitamin E
  • Niacin
  • Simvastatin
  • alpha-Tocopherol
  • Selenium
  • Ascorbic Acid