HYPERLIPIDEMIA Normalization of plasma lipoprotein concentrations in patients

The oral administration of neomycin or niacin as single-drug therapy can significantly lower total and low-density lipoprotein cholesterol concentrations in patients with type II hyperlipoproteinemia. However, in the majority of patients treated with one of these drugs as sole therapy plasma lipid and lipoprotein concentrations do not normalize. The effect of combined neomycin (2 g/day) and niacin (3 g/day) treatment on the plasma lipoprotein concentrations was determined in 25 type II hyperlipoproteinemic patients in a double-blind, randomized, placebo-controlled, crossover clinical trial. Treatment with neomycin was well tolerated by all 25 study patients and significantly reduced total and low-density lipoprotein cholesterol concentrations by 23% and 29%, respectively (p < .05). In contrast to the well-tolerated neomycin regimen, 11 patients (44%) were unable to continue niacin treatment because of adverse side effects. In the 14 patients treated with both neomycin and niacin, niacin further lowered the concentrations of total and low-density lipoprotein cholesterol by 18% and 25%, respectively, and increased high-density lipoprotein cholesterol by 32% (p < .05) compared with that in the patients receiving neomycin plus niacin placebo. Compared with diet-only therapy, combined treatment with neomycin plus niacin reduced the total plasma cholesterol concentration by 36%, low-density lipoprotein cholesterol by 45%, and the low-density lipoprotein/high-density lipoprotein ratio by 46% and it increased plasma high-density lipoprotein concentrations by 24% (p < .001). During the study, 80% of all the study patients and 92% of the patients who complied with the combined regimen normalized their total and low-density lipoprotein concentrations. No serious or irreversible adverse side effects were detected during combination neomycin/niacin treatment. These results indicate that the lipoprotein concentrations in a majority of type II hyperlipoproteinemic patients can be safely normalized by either therapy with neomycin only or by combined treatment with neomycin/niacin. Circulation 70, No. 6, 1004-1011, 1984. EPIDEMIOLOGIC, METABOLIC, AND GENETIC studies in man have long demonstrated an association between the plasma lipoproteins and coronary heart disease (CHD).' The issue of a possible cause and effect relationship between lipoproteins and atherogenesis as well as the possibility of interfering with the development ofCHD by lowering total and low-density lipoprotein cholesterol concentrations have been evaluated by the Lipid Research Clinics (LRC) program.' 2 Using a double-blind, randomized, placeboFrom the Molecular Disease Branch and The Mathematical and Applied Statistics Branch of National Heart, Lung, and Blood Institute, and The Clinical Center, National Institutes of Health, Bethesda. Address for correspondence: Jeffrey M. Hoeg, M.D., Building 10, Room 7N1 14, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20205. Received June 11, 1984; revision accepted Aug. 23, 1984. controlled clinical trial, the LRC investigators determined that lowering the total and low-density lipoprotein plasma cholesterol concentrations by diet and drug treatment significantly reduced the incidence of CHD. ' In addition, a dose-response relationship was noted.2 Therefore, lowering total and low-density lipoprotein cholesterol concentrations by pharmacologic means has been conclusively demonstrated to prevent CHD. Currently the bile acid sequestrants cholestyramine and colestipol and the B-complex vitamin niacin are considered the hypocholesterolemic drugs of choice for patients with type II hyperlipoproteinemia. However, up to 30% of patients cannot tolerate cholestyramine because of unpalatability and gastrointestinal side effects.34 Up to 68% of patients treated with choCIRCULATION 1004 by gest on N ovem er 8, 2017 http://ciajournals.org/ D ow nladed from THERAPY AND PREVENTION-HYPERLIPIDEMIA lestyramine suffer at least one adverse side effect of the drug2 and the cost of the drug limits its widespread use. At 24 g/day, the cost to the patient for 1 month of cholestyramine treatment in the Washington, D.C., area approaches $170. Therefore, despite the efficacy of therapy with bile acid sequestrants in reducing CHD risk, the search for a well-tolerated, palatable, inexpensive, andc effective hypocholesterolemic drug regi-