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

Background: Both lipid-modifying therapy and antioxidant vitamins are thoug ht to have benefit in patients with coronary disease. We studied simvastati n-niacin and antioxidant-vitamin therapy, alone and together, for cardiovas cular protection in patients with coronary disease and low plasma levels of high-density lipoprotein (HDL) cholesterol. Methods: In a three-year, double-blind trial, 160 patients with coronary di sease, low HDL cholesterol levels, and normal low-density lipoprotein (LDL) cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, antioxidants, simvastatin-niacin plus antioxidant s, 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 a ntioxidant group and the placebo group; these levels changed substantially (by -42 percent and +26 percent, respectively) in the simvastatin-niacin gr oup. The protective increase in HDL2 with simvastatin plus niacin was atten uated by concurrent therapy with antioxidants. The average stenosis progres sed 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-n iacin plus antioxidants (P=0.004) and regressed by 0.4 percent with simvast atin-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 group given simvas tatin-niacin plus antioxidants. Conclusions: Simvastatin plus niacin provides marked clinical and angiograp hically measurable benefits in patients with coronary disease and low HDL l evels. The use of antioxidant vitamins in this setting must be questioned. (N Engl J Med 2001;345:1583-92.) Copyright (C) 2001 Massachusetts Medical S ociety.