Simvastatin and Niacin, Antioxidant Vitamins, or the Combination for the Prevention of Coronary Disease
B. Greg Brown, M.D., Ph.D., Xue-Qiao Zhao, M.D., Alan Chait, M.D., Lloyd D. Fisher, Ph.D., Marian C. Cheung, Ph.D., Josh S. Morse, B.S., Alice A. Dowdy, R.D., Emily K. Marino, M.S., Edward L. Bolson, M.S., Petar Alaupovic, Ph.D., Jiri Frohlich, M.D., Leny Serafini, B.S., Ellen Huss-Frechette, B.S., Shari Wang, B.S., Debbie DeAngelis, R.T., Arthur Dodek, M.D., and John J. Albers, Ph.D.
Background Both lipid-modifying therapy and antioxidant vitaminsare thought to have benefit in patients with coronary disease.We studied simvastatin–niacin and antioxidant-vitamintherapy, alone and together, for cardiovascular protection inpatients with coronary disease and low plasma levels of high-densitylipoprotein (HDL) cholesterol.
Methods In a three-year, double-blind trial, 160 patients withcoronary disease, low HDL cholesterol levels, and normal low-densitylipoprotein (LDL) cholesterol levels were randomly assignedto receive one of four regimens: simvastatin plus niacin, antioxidants,simvastatin–niacin plus antioxidants, or placebos. Theend points were arteriographic evidence of a change in coronarystenosis and the occurrence of a first cardiovascular event(death, myocardial infarction, stroke, or revascularization).
Results The mean levels of LDL and HDL cholesterol were unalteredin the antioxidant group and the placebo group; these levelschanged substantially (by –42 percent and +26 percent,respectively) in the simvastatin–niacin group. The protectiveincrease in HDL2 with simvastatin plus niacin was attenuatedby concurrent therapy with antioxidants. The average stenosisprogressed by 3.9 percent with placebos, 1.8 percent with antioxidants(P=0.16 for the comparison with the placebo group), and 0.7percent 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 24percent with placebos, 3 percent with simvastatin–niacinalone, 21 percent in the antioxidant-therapy group, and 14 percentin the group given simvastatin–niacin plus antioxidants.
Conclusions Simvastatin plus niacin provides marked clinicaland angiographically measurable benefits in patients with coronarydisease and low HDL levels. The use of antioxidant vitaminsin this setting must be questioned.
Source Information
From the Department of Medicine, Division of Cardiology (B.G.B., X.-Q.Z., J.S.M., E.L.B.), the Division of Metabolism, Endocrinology, and Nutrition (A.C., M.C.C., A.A.D., J.J.A.), and the Department of Biostatistics (L.D.F., E.K.M.), University of Washington School of Medicine, Seattle; the Oklahoma Medical Research Foundation, Oklahoma City (P.A.); and the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada (J.F.).
Other authors were Leny Serafini, B.S., Ellen Huss-Frechette, B.S., and Shari Wang, B.S. (Department of Medicine, University of Washington School of Medicine, Seattle); and Debbie DeAngelis, R.T., and Arthur Dodek, M.D. (Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada).
Address reprint requests to Dr. Brown at the Division of Cardiology, Box 356422, Health Sciences Bldg., Rm. A509, University of Washington, 1959 N.E. Pacific St., Seattle, WA 98195.
What Vitamins Should I Be Taking?
Blackman B. T., Opie L. H., Tulchinsky T.H., Nizan-Kaluski D., Willett W. C., Stampfer M. J.
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346:1914-1916, Jun 13, 2002.
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