Drugs in the Management of Lipid Disorders

  • David W. Bilheimer

Abstract

Clinical disease can occur when certain plasma lipoprotein levels are too low or too high.1 Frequently both abnormalities are found in the same patient, e.g., low high density lipoprotein (HDL) cholesterol and high low density lipoprotein (LDL) cholesterol in a patient at risk for atherosclerosis. The term dyslipoproteinemia has been used to refer to this general clinical problem, and the major clinical sequelae associated with dyslipoproteinemia include atherosclerosis, pancreatitis, and xanthoma formation.1 Reducing the risk for these clinical sequelae is the primary goal of therapy in the dyslipoproteinemic patient. If the dyslipoproteinemia cannot be adequately controlled with appropriate life style changes, dietary therapy including calorie reduction, or control of a primary causative disorder (e.g., diabetes mellitus; hypothyroidism), drug therapy must be considered in order to achieve the desired therapeutic goals.2,3

Keywords

Estrogen Aspirin Cardiol Hypothyroidism Lactone 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bilheimer DW. Disorders of lipid metabolism. In: Kelly WN, ed. Textbook of Internal Medicine. Philadelphia: Lippincott, 1989:2258–2269.Google Scholar
  2. 2.
    Expert Panel. Report of the National Cholesterol Education Program Expert Panel on detection, evaluation and treatment of high blood cholesterol in adults. Arch Intern Med 1988;148:36–69.CrossRefGoogle Scholar
  3. 3.
    Bilheimer DW. Evaluation of abnormal lipid profiles. In: Kelly WN, ed. Textbook of Internal Medicine, Philadelphia: Lippincott, 1989:2333–2339.Google Scholar
  4. 4.
    Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population. Am Heart J 1986;111:383–390.PubMedCrossRefGoogle Scholar
  5. 5.
    Castelli WP. Cardiovascular disease in women. Am J Obstet Gynecol 1988;158:1553–1560.PubMedGoogle Scholar
  6. 6.
    Slack J. Risks of ischaemic heart-disease in familial hyperlipoproteinemic states. Lancet 1969;2:1380–1382.PubMedCrossRefGoogle Scholar
  7. 7.
    Stone NJ, Levy RI, Frederickson DS, et al. Coronary artery disease in 116 kindred with familial type II hyperlipoproteinemia. Circulation 1974;49:476–488.PubMedGoogle Scholar
  8. 8.
    Wong ND, Cupples A, Ostfeld AM, et al. Risk factors for long-term coronary prognosis after myocardial infarction: the Framingham Study. Am J Epidemiol 1989;130:469–480.PubMedGoogle Scholar
  9. 9.
    Wild RA, Painter PC, Coulson PB, et al. Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1985;61:946–951.PubMedCrossRefGoogle Scholar
  10. 10.
    Grundy Sm, Goodman DS, Rifkind BM, et al. The place of HDL in cholesterol management: a perspective from the national cholesterol education program. Arch Intern Med 1989;149:505–510. PubMedCrossRefGoogle Scholar
  11. 11.
    Manninen V, Elo O, Frick H, et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki heart study. JAMA 1988;260:641–651.PubMedCrossRefGoogle Scholar
  12. 12.
    Frick MH, Elo O, Haapa K, et al. Helsinki heart study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia. N Engl J Med 1987;317:1237–1245.PubMedCrossRefGoogle Scholar
  13. 13.
    Knopp RH. Cardiovascular effects of endogenous and exogenous sex hormones over a woman’s lifetime. Am J Obstet Gynecol 1988;158:1630–1643.PubMedGoogle Scholar
  14. 14.
    Bilheimer DW, East C. Lipid-lowering agents.In: Williams RL, Brater DC, Mordenti J, eds. Rational Therapeutics.A Clinical Pharmacological Guide for the Health Professional. New York: Marcel Dekker, 1990:689–755. Google Scholar
  15. 15.
    Levy RI, Fredrickson DS, Shulman R, et al. Dietary and drug treatment of primary hyperlipoproteinemia. Ann Intern Med 1972;77:267–294.Google Scholar
  16. 16.
    Grundy SM. Treatment of hypercholesterolemia by interference with bile acid metabolism. Arch Intern Med 1972;130:638–648.PubMedCrossRefGoogle Scholar
  17. 17.
    Heel RC, Brogden RN, Pakes GE, et al. Colestipol: a review of its pharmacological properties and therapeutic efficacy in patients with hypercholesterolemia. Drugs 1980;19:161–180.PubMedCrossRefGoogle Scholar
  18. 18.
    Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986;232:34–47.PubMedCrossRefGoogle Scholar
  19. 19.
    Grundy SM. Bile acid resins: mechanisms of action. In: Fears R, ed. Pharmacological Control of Hyperlipidaemia. Barcelona: JR Prous Science Publishers, 1986:3–19.Google Scholar
  20. 20.
    Angelin B, Einarsson K, Hellstrom K, et al. Effects of cholestyramine and chenodeoxycholic acid on the metabolism of endogenous triglyceride in hyperlipoproteinemia. J Lipid Res 1978;19:1017–1024.PubMedGoogle Scholar
  21. 21.
    Lipid Research Clinics Program. The Lipid Research Clinics Primary Prevention Trial Results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984;251:365–374. CrossRefGoogle Scholar
  22. 22.
    Asano T, Pollard M, Madsen DC. Effects of cholestyramine on 1,2-dimethylhydrazine-induced enteric carcinoma in germfree rats. Proc Soc Exp Biol Med 1975;150:780–785.PubMedGoogle Scholar
  23. 23.
    Nigro ND, Bhadrachari N, Chromchai C. A rat model for studying colonic cancer: effect of cholestyramine on induced tumors. Dis Colon Rectum 1973;16:438–443.PubMedCrossRefGoogle Scholar
  24. 24.
    Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984;251:351–364. CrossRefGoogle Scholar
  25. 25.
    Hashim SA, Bergen SS Jr, Van Itallie TB. Experimental steatorrhea induced in man by bile acid sequestrant. Proc Soc Exp Biol Med 1961;106:173–175.PubMedGoogle Scholar
  26. 26.
    Kwiterovich PO Jr. Bile acid sequestrant resin therapy in children. In: Fears R, ed. Pharmacological Control of Hyperlipidemia. Barcelona: JR Prous Science Publishers, 1986:55–66.Google Scholar
  27. 27.
    West RJ, Lloyd JK. The effect of cholestyramine on intestinal absorption. Gut 1975;16:93–98.PubMedCrossRefGoogle Scholar
  28. 28.
    Hunninghake DB. Resin therapy: adverse effects and their management. In: Fears R, ed. Pharmacological Control of Hyperlipidemia. Barcelona: JR Prous Science Publishers, 1986:67–89.Google Scholar
  29. 29.
    Boyden TW, Totman L. Synergistic effects of probucol and cholestyramine to lower serum cholesterol. J Clin Pharmacol 1981;21:48–51.PubMedGoogle Scholar
  30. 30.
    Hoeg JM, Maher MB, Bailey KR, et al. Effects of combination cholestyramine-neomycin treatment on plasma lipoprotein concentrations in type II hyperlipoproteinemia. Am J Cardiol 1985;55:1282–1286.PubMedCrossRefGoogle Scholar
  31. 31.
    Angelin B, Ericksson M, Einarsson K. Combined treatment with cholestyramine and nicotinic acid in heterozygous familial hypercholesterolaemia: effects on biliary lipid composition. Eur J Clin Invest 1986;16:391–396.PubMedCrossRefGoogle Scholar
  32. 32.
    Series JJ, Caslake MJ, Kilday C, et al. Effect of combined therapy with beza-fibrate and cholestyramine on low-density lipoprotein metabolism in type Ha hypercholesterolemia. Metabolism 1989;38:153–158.PubMedCrossRefGoogle Scholar
  33. 33.
    Witztum JL. Intensive drug therapy of hypercholesterolemia. Am Heart J 1987;113:603–609.PubMedCrossRefGoogle Scholar
  34. 34.
    Illingworth DR, Bacon S. Treatment of heterozygous familial hypercholesterolemia with lipid-lowering drugs. Arteriosclerosis 1989;9(suppl I):I121–I134.PubMedGoogle Scholar
  35. 35.
    Forland SC, Feng Y, Cutler RE. Apparent reduced absorption of gemfibrozil when given with colestipol. J Clin Pharmacol 1990;30:29–32.PubMedGoogle Scholar
  36. 36.
    Levy RI, Fredrickson DS, Stone NJ, et al. Cholestyramine in type II hyperlipoproteinemia: a double-blind trial. Ann Intern Med 1973;79:51–58.PubMedGoogle Scholar
  37. 37.
    Brensike JF, Levy RI, Kelsey SF, et al. Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI type II coronary intervention study. Circulation 1984;69:313–324.PubMedCrossRefGoogle Scholar
  38. 38.
    Levy RI, Brensike JF, Epstein SE, et al. The influence of changes in lipid values induced by cholestyramine and diet on progression of coronary artery disease: results of the NHLBI type II coronary intervention study. Circulation 1984;69:325–337.PubMedCrossRefGoogle Scholar
  39. 39.
    Angelin B, Einarsson K. Cholestyramine in type Ha hyperlipoproteinemia: is low-dose treatment feasible? Atherosclerosis 1981;38:33–38. PubMedCrossRefGoogle Scholar
  40. 40.
    Witztum JL. Current approaches to drug therapy for the hypercholesterole-mic patient. Circulation 1989;80:1101–1114.PubMedCrossRefGoogle Scholar
  41. 41.
    Sirtori M, Franceshini G, Gianfranceshi G, et al. Microporous cholestyramine in suspension form. Lancet 1982;2:383.PubMedCrossRefGoogle Scholar
  42. 42.
    Crouse JR III. Hypertriglyceridemia: a contraindication to the use of bile acid binding resins. Am J Med 1987;83:243–248.PubMedCrossRefGoogle Scholar
  43. 43.
    Report of the Committee of Principal Investigators. W.H.O. Cooperative Trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: mortality follow-up. Lancet 1980;2:379–385. Google Scholar
  44. 44.
    Havel RJ, Kane JP. Drugs and lipid metabolism. Annu Rev Pharmacol 1973;13:287–308.PubMedCrossRefGoogle Scholar
  45. 45.
    Gugler R. Clinical pharmacokinetics of hypolipidaemic drugs. Clin Pharma-cokinet 1978;3:425–439.CrossRefGoogle Scholar
  46. 46.
    Cayen MN. Disposition, metabolism and pharmacokinetics of antihyperli-pidemic agents in laboratory animals and man. Pharmacol Ther 1985;29:157–204.PubMedCrossRefGoogle Scholar
  47. 47.
    Witiak DT, Newman HAI, Feller DR. Clofibrate and Related Analogues. New York: Marcel Dekker, 1977.Google Scholar
  48. Marks J, ed. Dyslipoproteinemia—aspects of gemfibrozil therapy. In: Research and Clinical Forums. Vol. 4. Kent, England:[Publisher], 1982. Google Scholar
  49. 49.
    Newton RS, Krause BR. Mechanisms of action of gemfibrozil: comparison of studies in the rat to clinical efficacy. In: Fears R, ed. Pharmacological Control of Hyperlipidaemia, Barcelona: JR Prous Science Publishers, 1986:171–186.Google Scholar
  50. 50.
    Todd PA, Ward A. Gemfibrozil: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in dyslipidaemia. Drugs 1988;36:314–339.PubMedCrossRefGoogle Scholar
  51. 51.
    Eisenberg S, Gavish D, Kleinman Y. Bezafibrate. In: Fears R, ed. Pharmacological Control of Hyperlipidaemia, Barcelona: JR Prous Science Publishers, 1986:145–169.Google Scholar
  52. 52.
    Monk JP, Todd PA. Bezafibrate: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hyperlipidaemia. Drugs 1987;33:539–576.PubMedCrossRefGoogle Scholar
  53. 53.
    Blane GF, Bogaievsky Y, Bonnefous F. Fenofibrate: influence on circulating lipids and side-effects in medium and long-term clinical use. In: Fears R, ed. Pharmacological Control of Hyperlipidaemia. Barcelona: JR Prous Science Publishers, 1986:187–216.Google Scholar
  54. 54.
    Kloer H. Structure and biochemical effects of fenofibrate. Am J Med 1987;83(5B):3–8. PubMedCrossRefGoogle Scholar
  55. 55.
    Grundy SM, Vega GL. Fibric acids: effects on lipids and lipoprotein metabolism. Am J Med 1987;83(5B):9–20. PubMedCrossRefGoogle Scholar
  56. 56.
    Chapman JM. Pharmacology of fenofibrate. Am J Med 1987;83(5B):21–25. PubMedCrossRefGoogle Scholar
  57. 57.
    Blane GF. Comparative toxicity and safety profile of fenofibrate and other fibric acid derivatives. Am J Med 1987;83(5B):26–36. PubMedCrossRefGoogle Scholar
  58. 58.
    Palmer RH. Effects of fibric acid derivatives on biliary lipid composition. Am J Med 1987;83(5B):37–43. PubMedCrossRefGoogle Scholar
  59. 59.
    Hunninghake DB, Peters JR. Effect of fibric acid derivatives on blood lipid and lipoprotein levels. Am J Med 1987;83(5B):44–49. PubMedCrossRefGoogle Scholar
  60. 60.
    Knopp RH, Brown WV, Dujovne CA, et al. Effects of fenofibrate on plasma lipoproteins in hypercholesterolemia and combined hyperlipidemia. Am J Med 1987;83(5B):50–59. PubMedCrossRefGoogle Scholar
  61. 61.
    Sirtori CR, Franceschini G. Effects of fibrates on serum lipids and atherosclerosis. Pharmacol Ther 1988;37:167–191.PubMedCrossRefGoogle Scholar
  62. 62.
    Greten H, Laible V, Zipperle G, et al. Comparison of assay methods for selective measurement of plasma lipase: the effect of clofibrate on hepatic and lipoprotein lipase in normals and patients with hypertriglyceridemia. Atherosclerosis 1977;26:563–572.PubMedCrossRefGoogle Scholar
  63. 63.
    Nikkila EA, Huttunen JK, Ehnholm C. Effect of clofibrate on postheparin plasma triglyceride lipase activities in patients with hypertriglyceridemia. Metabolism 1977;26:179–186.PubMedCrossRefGoogle Scholar
  64. 64.
    Kissebah AH, Adams PW, Harrington P, et al. The mechanism of action of clofibrate and tetranicotinoylfructose (Bradilan) on the kinetics of plasma free fatty acid and triglyceride transport in type IV and type V hypertriglyceri-daemia. Eur J Clin Invest 1974;4:163–174.PubMedGoogle Scholar
  65. 65.
    Kesaniemi YA, Beltz WF, Grundy SM. Comparison of clofibrate and caloric restriction on kinetics of very low density lipoprotein triglycerides. Arteriosclerosis 1985;5:153–161.PubMedCrossRefGoogle Scholar
  66. 66.
    Walton KW, Scott PJ, Verrier Jones J, et al. Studies on low-density lipoprotein turnover in relation to Atromid therapy. J Atheroscler Res 1963;3:396–414. CrossRefGoogle Scholar
  67. 67.
    Coronary Drug Project Research Group. Gallbladder disease as a side effect of drugs influencing lipid metabolism. Experience in the Coronary Drug Project. N Engl J Med 1977;296:1185–1190. CrossRefGoogle Scholar
  68. 68.
    Report of the Committee of Principal Investigators. W.H.O. Cooperative Trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Lancet 1984;2:600–604. Google Scholar
  69. 69.
    Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. JAMA 1975;231:360–381.CrossRefGoogle Scholar
  70. 70.
    Rimon D, Ludatscher R, Cohen L. Clofibrate-induced muscular syndrome: case report with ultrastructural findings and review of the literature. Isr J Med Sci 1984;20:1082–1086.PubMedGoogle Scholar
  71. 71.
    Hunninghake DB. Drug interactions involving hypolipidemic drugs. In: Petrie JC, ed. Cardiovascular and Respiratory Disease Therapy. New York: Elsevier/North Holland Biomedical Press, 1980:79–105.Google Scholar
  72. 72.
    Report from the Committee of Principal Investigators. A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate Br Heart J 1978;40:1069–1118.Google Scholar
  73. 73.
    Hunninghake DB, Tucker DR, Azarnoff DL. Long-term effects of clofibrate (Atromid-S) on serum lipids in man. Circulation 1969;39:675–683.PubMedGoogle Scholar
  74. 74.
    Stuyt PMJ, Demacker PNM, Van’t Laar A. Long-term treatment of type III hyperlipoproteinemia with clofibrate. Atherosclerosis 1981;40:329–336. PubMedCrossRefGoogle Scholar
  75. 75.
    Hoogwerf BJ, Bantle JP, Kuba K, et al. Treatment of type III hyperlipoproteinemia with four different treatment regimens. Atherosclerosis 1984; 51:251–259.PubMedCrossRefGoogle Scholar
  76. 76.
    Nestel PJ, Hunt D7E Wahlqvist ML. Clofibrate raises plasma apoprotein A-l and HDL-cholesterol concentrations. Atherosclerosis 1980;37:625–629.PubMedCrossRefGoogle Scholar
  77. 77.
    Evans JR, Forland SC, Cutler RE. The effect of renal function on the pharmacokinetics of gemfibrozil. J Clin Pharmacol 1987;27:994–1000.PubMedGoogle Scholar
  78. 78.
    Saku K, Gartside PS, Hynd BA, et al. Mechanism of action of gemfibrozil on lipoprotein metabolism. J Clin Invest 1985;75:1702–1712.PubMedCrossRefGoogle Scholar
  79. 79.
    Weintraub MS, Eisenberg S, Breslow JL. Different patterns of postprandial lipoprotein metabolism in normal, type IIa, type III, and type IV hyperlipo-proteinemic individuals: effects of treatment with cholestyramine and gemfibrozil. J Clin Invest 1987;79:1110–1119.PubMedCrossRefGoogle Scholar
  80. 80.
    Houlston R, Quiney J, Watts GF, et al. Gemfibrozil in the treatment of resistant familial hypercholesterolemia and type III hyperlipoproteinaemia. J R Soc Med 1988;81:274–276.PubMedGoogle Scholar
  81. 81.
    Vega GL, Grundy SM. Gemfibrozil therapy in primary hypertriglyceridemia associated with coronary heart disease. JAMA 1985;253:2398–2403.PubMedCrossRefGoogle Scholar
  82. 82.
    Shepherd J, Caslake MJ, Lorimer AR, et al. Fenofibrate reduces low density lipoprotein catabolism in hypertriglyceridemic subjects. Arteriosclerosis 1985;5:162–168.PubMedCrossRefGoogle Scholar
  83. 83.
    Malmendier CL, Delcroix C. Effects of fenofibrate on high and low density lipoprotein metabolism in heterozygous familial hypercholesterolemia. Atherosclerosis 1985;55:161–169.PubMedCrossRefGoogle Scholar
  84. 84.
    Kleinman Y, Eisenberg S, Oschry Y, et al. Defective metabolism of hypertriglyceridemic low density lipoprotein in cultered human skin fibroblasts: normalization with bezafibrate therapy. J Clin Invest 1985;75:1796–1803.PubMedCrossRefGoogle Scholar
  85. 85.
    Tikkanen MJ, Helve E, Jaattela A, et al. Comparison between lovastatin and gemfibrozil in the treatment of primary hypercholesterolemia: the Finnish multicenter study. Am J Cardiol 1988;62:35J–43J.PubMedCrossRefGoogle Scholar
  86. 86.
    Eisenberg S. Lipoprotein abnormalities in hypertriglyceridemia: significance in atherosclerosis. Am Heart J 1987;113:555–561.PubMedCrossRefGoogle Scholar
  87. 87.
    Vega GL, Grundy SM. Comparison of lovastatin and gemfibrozil in normo-lipidemic patients with hypoalphalipoproteinernia. JAMA 1989; 262:3148–3153.PubMedCrossRefGoogle Scholar
  88. 88.
    Laustiola K, Lassila R, Koskinen P, et al. Gemfibrozil decreases platelet reactivity in patients with hypercholesterolemia during physical stress. Clin Pharmacol Ther 1988;43:302–307.PubMedCrossRefGoogle Scholar
  89. 89.
    Torstila I, Kaukola S, Manninen V, et al. Plasma prekallikrein, kallikrein inhibitors, kininogen and lipids during gemfibrozil treatment in type II dyslipi-daemia. Acta Med Scand [Suppl] 1982;668:123–129.Google Scholar
  90. 90.
    Leiss O, von Bergmann K, Gnasso A, et al. Effect of gemfibrozil on biliary lipid metabolism in normolipidemic subjects. Metabolism 1985;34:74–82.PubMedCrossRefGoogle Scholar
  91. 91.
    Hall MJ, Nelson LM, Russel RI, et al. Gemfibrozil—the effect on biliary cholesterol saturation of a new lipid-lowering agent and its comparison with clofibrate. Atherosclerosis 1981;39:511–516.PubMedCrossRefGoogle Scholar
  92. 92.
    Pasternack A, Vantinnen T, Solakivi T, et al. Normalization of lipoprotein lipase and hepatic lipase by gemfibrozil results in correction of lipoprotein abnormalities in chronic renal failure. Clin Nephrol 1987;27:163–168.PubMedGoogle Scholar
  93. 93.
    Lopid (Gemfibrozil) package insert. Parke-Davis, January 1989.Google Scholar
  94. 94.
    De La Iglesia FA, Lewis JE, Buchanan RA, et al. Light and electron microscopy of liver in hyperlipoproteinemic patients under long-term gemfibrozil treatment. Atherosclerosis 1982;43:19–37.CrossRefGoogle Scholar
  95. 95.
    Tobert JA. Letter to the editor. N Engl J Med 1988;318:48.CrossRefGoogle Scholar
  96. 96.
    Marais GE, Larson KK. Rhabdomyolysis and acute renal failure induced by combination lovastatin and gemfibrozil therapy. Ann Intern Med 1990; 112:228–230.PubMedGoogle Scholar
  97. 97.
    Manninen V, Huttunen JK, Heinonen OP, et al. Relation between baseline lipid and lipoprotein values and the incidence of coronary heart disease in the Helsinki Heart Study. Am J Cardiol 1989;63:42H–47H.PubMedCrossRefGoogle Scholar
  98. 98.
    Leaf DA, Connor WE, Illingworth DR, et al. The hypolipidemic effects of gemfibrozil in type V hyperlipidemia. JAMA 1989;262:3154–3160.PubMedCrossRefGoogle Scholar
  99. 99.
    Kostner G, Klein G, Krempler F. Can serum Lp(a) concentrations be lowered by drugs and/or diet? In: Carlson LA, Olsson AG, eds. Treatment of Hyperlipoproteinemia. New York: Raven Press, 1984:151–156.Google Scholar
  100. 100.
    Brown MS, Goldstein JL. Multivalent feedback regulation of HMG Co A reductase, a control mechanism coordinating isoprenoid synthesis and cell growth. J Lipid Res 1980;21:505–517.PubMedGoogle Scholar
  101. 101.
    Rudney H, Sexton RC. Regulation of cholesterol biosynthesis. Annu Rev Nutr 1986;6:245–272.PubMedCrossRefGoogle Scholar
  102. 102.
    Grundy SM. HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med 1988;319:24–33.PubMedCrossRefGoogle Scholar
  103. 103.
    Mabuchi H, Takeda R. Inhibitors of 3-hydroxy-3-metJiylglutaryl coenzyme A reductase: compactin and its analogues. In: Fears R, ed. Pharmacological Control of Hyperlipidemia. Barcelona: JR Prous Science Publishers, 1986: 251–261.Google Scholar
  104. 104.
    Illingworth DR. Specific inhibitors of cholesterol biosynthesis as hypo-cholesterolemic agents in humans: mevinolin and compactin. In: Fears R, ed. Pharmacological Control of Hyperlipidemia. Barcelona: Prous JR Science Publishers, 1986:231–249.Google Scholar
  105. 105.
    Hoeg JM, Brewer HB Jr. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in the treatment of hypercholesterolemia. JAMA 1987;258:3532–3536.PubMedCrossRefGoogle Scholar
  106. 106.
    Henwood JM, Heel RC. Lovastatin: a preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidemia. Drugs 1988;36:429–454.PubMedCrossRefGoogle Scholar
  107. 107.
    Kovanen PT, Bilheimer DW, Goldstein JL, et al. Regulatory role for hepatic low density lipoprotein receptors in vivo in the dog. Proc Natl Acad Sci USA 1981;78:1194–1198.PubMedCrossRefGoogle Scholar
  108. 108.
    Bilheimer DW, Grundy SM, Brown MS, et al. Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proc Natl Acad Sci USA 1983;80:4124–4128.PubMedCrossRefGoogle Scholar
  109. 109.
    Grundy SM, Vega GL. Influences of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia. J Lipid Res 1985; 26:1464–1475.PubMedGoogle Scholar
  110. 110.
    Vega GL, East C, Grundy SM. Lovastatin therapy in familial dysbetalipo-proteinemia: effects on kinetics of apolipoprotein B. Atherosclerosis 1988; 70:131–143.PubMedCrossRefGoogle Scholar
  111. 111.
    Thiery J, Armstrong VW, Schleef J, et al. Serum lipoprotein Lp(a) concentrations are not influenced by HMG CoA reductase inhibitor. Klin Wochenschr 1988;66:462–463.PubMedCrossRefGoogle Scholar
  112. 112.
    Jurgens G, Ashy A, Zenker G. Raised serum lipoprotein during treatment with lovastatin. Lancet 1989;1:911–912.PubMedCrossRefGoogle Scholar
  113. 113.
    Grundy SM, Bilheimer DW. Inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase by mevinolin in familial hypercholesterolemia heterozygotes: effects on cholesterol balance. Proc Natl Acad Sci USA 1984;81:2538–2542.PubMedCrossRefGoogle Scholar
  114. 114.
    Parker TS, McNamara DJ, Brown CD, et al. Plasma mevalonate as a measure of cholesterol synthesis in man. J Clin Invest 1984;74:795–804.PubMedCrossRefGoogle Scholar
  115. 115.
    Tobert J A. Efficacy and long-term adverse effect pattern of lovastatin. Am J Cardiol 1988;62:28J–34J.PubMedCrossRefGoogle Scholar
  116. 116.
    Lovastatin Study Group II. Therapeutic response to lovastatin (mevinolin) in nonfamilial hypercholesterolemia. JAMA 1986;256:2829–2834.CrossRefGoogle Scholar
  117. 117.
    Lovastatin Study Group III. A multicenter comparison of lovastatin and cholestyramine therapy for severe primary hypercholesterolemia. JAMA 1988;260:359–366.CrossRefGoogle Scholar
  118. 118.
    Havel RJ, Hunninghake DB, Illingworth DR, et al. Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia: a multicenter study. Ann Intern Med 1987;107:609–615.PubMedGoogle Scholar
  119. 119.
    MacDonald JS, Gerson RJ, Kornbrust DJ, et al. Preclinical evaluation of lovastatin. Am J Cardiol 1988;62:16J–27J.PubMedCrossRefGoogle Scholar
  120. 120.
    Hunninghake DB, Miller VT, Stein I, et al. Lovastatin: follow-up ophthalmologic data. JAMA 1988;259:354–355.PubMedCrossRefGoogle Scholar
  121. 121.
    Laue L, Hoeg JM, Barnes K, et al. The effect of mevinolin on steroidogenesis in patients with defects in the low density lipoprotein receptor pathway. J Clin Endocrinol Metab 1987;64:531–535.PubMedCrossRefGoogle Scholar
  122. 122.
    Fojo SS, Hoeg JM, Lackner KJ, et al. Adrenocortical function in type II hyperlipoproteinemic patients treated with lovastatin (mevinolin). Horm Metab Res 1987;19:648–652.PubMedCrossRefGoogle Scholar
  123. 123.
    Thompson GR, Ford J, Jenkinson M, et al. Efficacy of mevinolin as adjuvant therapy for refractory familial hypercholesterolemia. Q J Med 1986;60:803–811.PubMedGoogle Scholar
  124. 124.
    Farnsworth WH, Hoeg JM, Maher M, et al. Testicular function in type II hyperlipoproteinemic patients treated with lovastatin (Mevacor) or neomycin. J Clin Endocrinol Metab 1987;65:546–550.PubMedCrossRefGoogle Scholar
  125. 125.
    Norman DJ, Illingworth DR, Munson J, et al. Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin. N Engl J Med 1988;318:46–47.PubMedCrossRefGoogle Scholar
  126. 126.
    East C, Alivazatos PA, Grundy SM, et al. Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation. N Engl J Med 1988;318:47–48.PubMedCrossRefGoogle Scholar
  127. 127.
    Reaven P, Witztum JL. Lovastatin, nicotinic acid, and rhabdomyolysis. Ann Intern Med 1988;109:597–598.PubMedGoogle Scholar
  128. 128.
    Ayanian JZ, Fuchs CS, Stone RM. Lovastatin and rhabdomyolysis. Ann Intern Med 1988;109:682.PubMedGoogle Scholar
  129. 129.
    Corpier CL, Jones PH, Suki WN, et al. Rhabdomyolysis and renal injury with lovastatin use. JAMA 1988;260:239–241.PubMedCrossRefGoogle Scholar
  130. 130.
    Edelman S, Witzum JL. Hyperkalemia during treatment with HMG-CoA reductase inhibitor. N Engl J Med 1989;320:1219–1220.PubMedGoogle Scholar
  131. 131.
    Israeli A, Raveh D, Arnon R, et al. Lovastatin and elevated creatine kinase: results of rechallange. Lancet 1989; 1:725.PubMedCrossRefGoogle Scholar
  132. 132.
    Mevacor (lovastatin) package insert, Merck Sharp & Dohme, West Point, PA (December 1988).Google Scholar
  133. 133.
    Illingworth DR. Long term administration of lovastatin in the treatment of hypercholesterolemia. Eur Heart J 1987;8(suppl E):103–111. PubMedGoogle Scholar
  134. 134.
    East C, Bilheimer DW, Grundy SM. Combination drug therapy for familial combined hyperlipidemia. Ann Intern Med 1988;109:25–32.PubMedGoogle Scholar
  135. 135.
    Hoeg JM, Maher MB, Zech LA, et al. Effectiveness of mevinolin on plasma lipoprotein concentrations in type II hyperlipoproteinemia. Am J Cardiol 1986;57:933–939.PubMedCrossRefGoogle Scholar
  136. 136.
    Uauy R, Vega GL, Grundy SM, et al. Lovastatin therapy in receptor-negative homozygous familial hypercholesterolemia: lack of effect on low-density lipoprotein concentrations or turnover. J Pediatr 1988;113:387–392.PubMedCrossRefGoogle Scholar
  137. 137.
    East CA, Grundy SM, Bilheimer DW. Preliminary report: treatment of type 3 hyperlipoproteinemia with mevinolin. Metabolism 1986;35:97–98.PubMedCrossRefGoogle Scholar
  138. 138.
    Garg A, Grundy SM. Lovastatin for lowering cholesterol levels in non-insulin-dependent diabetes mellitus. N Engl J Med 1988;318:81–86.PubMedCrossRefGoogle Scholar
  139. 139.
    Garg A, Grundy SM. Gemfibrozil alone and in combination with lovastatin for treatment of hypertriglyceridemia in NIDDM. Diabetes 1989;38:364–372.PubMedCrossRefGoogle Scholar
  140. 140.
    Vega GL, Grundy SM. Lovastatin therapy in nephrotic hyperlipidemia: effects on lipoprotein metabolism. Kidney Int 1988;33:1160–1168.PubMedCrossRefGoogle Scholar
  141. 141.
    Brown BG, Lin JT, Schaefer SM, et al. Niacin or lovastatin, combined with colestipol, regress coronary atherosclerosis and prevent clinical events in men with elevated apolipoprotein B. Circulation 1989:80(suppl II): 11–266. Google Scholar
  142. 142.
    Hoeg JM, Maher MB, Bailey KR, et al. The effects of mevinolin and neomycin alone and in combination on plasma lipid and lipoprotein concentrations in type II hyperlipoproteinemia. Atherosclerosis 1986;60:209–214.PubMedCrossRefGoogle Scholar
  143. 143.
    Helve E, Tikkanen MJ. Comparison of lovastatin and probucol in treatment of familial and non-familial hypercholesterolemia: different effects on lipoprotein profiles. Atherosclerosis 1988;72:189–197.PubMedCrossRefGoogle Scholar
  144. 144.
    Joven J, Masana L, Vilella E, et al. Lipid-lowering drugs in treatment of hyperlipidaemia associated with nephrotic syndrome. Lancet 1989; 1:1029.PubMedCrossRefGoogle Scholar
  145. 145.
    Schulzeck P, Bojanovski M, Jochim A, et al. Comparison between simvastatin and bezafibrate in effect on plasma lipoproteins and apolipoproteins in primary hypercholesterolemia. Lancet 1988;1:611–612.PubMedCrossRefGoogle Scholar
  146. 146.
    Mol MJTM, Erkelens DW, Gevers Leuven JA, et al. Simvastatin (MK-733): a potent cholesterol synthesis inhibitor in heterozygous familial hypercholesterolemia. Atherosclerosis 1988;69:131–137. PubMedCrossRefGoogle Scholar
  147. 147.
    Molgaard J, von Schenk H, Olsson AG. Effects of simvastatin on plasma lipid, lipoprotein and apolipoprotein concentrations in hypercholesterolemia. Eur Heart J 1988;9:541–551.PubMedGoogle Scholar
  148. 148.
    Leclerq V, Harvengt C. Simvastatin (MK 733) in heterozygous familial hypercholesterolemia: a two-year trial. Int J Clin Pharmacol Ther and Toxicol 1989;27:76–81.Google Scholar
  149. 149.
    Pietro DA, Alexander S, Mantell G, et al. Effects of simvastatin and probucol in hypercholesterolemia (simvastatin multicenter study group II). Am J Cardiol 1989;63:682–686.PubMedCrossRefGoogle Scholar
  150. 150.
    Mabuchi H, Kamon N, Fujita H, et al. Effects of CS-514 on serum lipoprotein lipid and apolipoprotein levels in patients with familial hypercholesterolemia. Metabolism 1987;36:475–479.PubMedCrossRefGoogle Scholar
  151. 151.
    Saku K, Sasaki J, Arakawa K. Long-term effect of CS-514 (HMG-CoA reductase inhibitor) on serum lipids, lipoproteins, and apolipoproteins in patients with hypercholesterolemia. Curr Ther Res 1987;42:491–500.Google Scholar
  152. 152.
    Yoshino G, Kazumi T, Iwai M, et al. Long-term treatment of hypercholester-olemic non-insulin dependent diabetics (NIDDM) with pravastatin (CS-514). Atherosclerosis 1989;75:67–72.PubMedCrossRefGoogle Scholar
  153. 153.
    Gey KF, Carlson LA, eds. Metabolic Effects of Nicotinic Acid and Its Derivatives. Bern: H. Huber Publishers, 1971.Google Scholar
  154. 154.
    Hotz W. Nicotinic acid and its derivatives: a short survey. Adv Lipid Res 1983;20:195–217.PubMedGoogle Scholar
  155. 155.
    Olsson AG, Walldius G, Wahlberg G. Pharmacological control of hyperlipidaemia: nicotinic acid and its analogues—mechanisms of action, effects and clinical usage. In: Fears R, ed. Pharmacological Control of Hyperlipidaemia. Barcelona: JR Prous Science Publishers, 1986:217–230.Google Scholar
  156. 156.
    Fumagalli R. Pharmacokinetics of nicotinic acid and some of its derivatives. In: Gey KF, Carlson LA, eds. Metabolic Effects of Nicotinic Acid and Its Derivatives. Bern: H. Huber Publishers, 1971:33–49.Google Scholar
  157. 157.
    Mrochek JE, Jolley RL, Young DS, et al. Metabolic response of humans to ingestion of nicotinic acid and nicotinamide. Clin Chem 1976;22:1821–1827.PubMedGoogle Scholar
  158. 158.
    Carlson LA. Consequences of inhibition of normal and excessive lipid mobilization: studies with nicotinic acid. Prog Biochem Pharmacol 1967;3:151–166.Google Scholar
  159. 159.
    Grundy SM, Mok HYI, Zech L, et al. Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man. J Lipid Res 1981;22:24–36.PubMedGoogle Scholar
  160. 160.
    Miettinen TA. Effect of nicotinic acid on the fecal excretion of neutral sterols and bile acids. In: Gey KF, Carlson LA, eds. Metabolic Effects of Nicotinic acid and Its Derivatives. Bern: H. Huber Publishers, 1971:677–686.Google Scholar
  161. 161.
    Langer T, Levy RL The effect of nicotinic acid on the turnover of low density lipoproteins in type II hyperlipoproteinemia. In: Gey KF, Carlson LA, eds. Metabolic Effects of Nicotinic Acid and Its Derivatives. Bern: H. Huber Publishers, 1971:641–647.Google Scholar
  162. 162.
    Carlson LA, Olsson AG, Ballantyne D. On the rise in low density and high density lipoproteins in response to treatment of hypertriglyceridemia in type IV and type V hyperlipoproteinemias. Atherosclerosis 1977;26:603–609.PubMedCrossRefGoogle Scholar
  163. 163.
    Boberg J, Carlson LA, Froberg S, et al. Effects of chronic treatment with nicotinic acid on intravenous fat tolerance and post-heparin lipase activity in man. In: Gey KF, Carlson LA, eds. Metabolic Effects of Nicotinic Acid and Its Derivatives. Bern: H. Huber Publishers, 1971:465–470.Google Scholar
  164. 164.
    Nikkila EA. Effect of nicotinic acid on adipose tissue lipoprotein lipase and removal rate of plasma triglycerides. In: Gey KF, Carlson LA, eds. Metabolic Effects of Nicotinic Acid and Its Derivatives. Bern: H. Huber Publishers, 1971:487–496.Google Scholar
  165. 165.
    Packard CJ, Stewart JM, Third JLHC, et al. Effects of nicotinic acid therapy on high-density lipoprotein metabolism in type II and type IV hyperlipo-proteinaemia. Biochim Biophys Acta 1980;618:53–62.PubMedGoogle Scholar
  166. 166.
    Shephard J, Packard CJ, Patsch JR, et al. Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism. J Clin Invest 1979;63:858–867.CrossRefGoogle Scholar
  167. 167.
    Atmeh RF, Shepherd J, Packard CJ. Subpopulations of apolipoprotein A-l in human high-density lipoproteins: their metabolic properties and response to drug therapy. Biochim Biophys Acta 1983;751:175–188.PubMedGoogle Scholar
  168. 168.
    Svedmyr N, Harthon L, Lundholm L. Dose-response relationship between concentration of free nicotinic acid concentration of plasma and some metabolic and circulatory effects after administration of nicotinic acid and pen-taerythritoltetranicotinate in man. In: Gey KF, Carlson LA, eds. Metabolic Effects of Nicotinic Acid and Its Derivatives. Bern: H. Huber Publishers, 1971:1085–1098. Google Scholar
  169. 169.
    Phillips WS, Lightman SL. Is cutaneous flushing prostaglandin mediated? Lancet 1981;1:754–756.PubMedCrossRefGoogle Scholar
  170. 170.
    Olsson AG, Carlson LA, Anggard E, et al. Prostacyclin production augmented in the short term by nicotinic acid. Lancet 1983;2:565–566.PubMedCrossRefGoogle Scholar
  171. 171.
    Parsons WB Jr. Studies of nicotinic acid use in hypercholesterolemia. Arch Intern Med 1961;107:653–667.PubMedGoogle Scholar
  172. 172.
    Berge KG, Achor RWP, Christensen NA, et al. Hypercholesterolemia and nicotinic acid: a long term study. Am J Med 1961;31:24–36.CrossRefGoogle Scholar
  173. 173.
    Sugarman AA, Clark CG. Jaundice following the administration of niacin. JAMA 1974;228:202.CrossRefGoogle Scholar
  174. 174.
    Einstein N, Baker A, Galper J, et al. Jaundice due to nicotinic acid therapy. Dig Dis 1975;20:282–286.CrossRefGoogle Scholar
  175. 175.
    Blankenhorn DH, Nessim SA, Johnson RL, et al. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA 1987;257:3233–3240.PubMedCrossRefGoogle Scholar
  176. 176.
    Miettinen TA, Taskinen M-R, Pelkonen R, et al. Glucose tolerance and plasma insulin in man during acute and chronic administration of nicotinic acid. Acta Med Scand 1969;186:247–253.PubMedCrossRefGoogle Scholar
  177. 177.
    Zavaroni I, Bonora E, Pagliara M, et al. Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance. N Engl J Med 1989;320:702–706.PubMedCrossRefGoogle Scholar
  178. 178.
    Kaplan NM. The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med 1989;149:1514–1520.PubMedCrossRefGoogle Scholar
  179. 179.
    Millay RH, Klein ML, Illingworth DR. Niacin maculopathy. Ophthalmology 1988;95:930–936.PubMedGoogle Scholar
  180. 180.
    Litin SC, Anderson CF. Nicotinic acid-associated myopathy: a report of three cases. Am J Med 1989;86:481–483.PubMedCrossRefGoogle Scholar
  181. 181.
    Cashin-Hemphill L, Spencer CA, Nicoloff JT, et al. Alterations in serum thyroid hormonal indices with colestipol-niacin therapy. Ann Intern Med 1987;107:324–329.PubMedGoogle Scholar
  182. 182.
    Parsons WB Jr, Flinn JH. Reduction of serum cholesterol levels and beta-lipoprotein cholesterol levels by nicotinic acid. Arch Intern Med 1959; 103:783–790.Google Scholar
  183. 183.
    Parsons WB Jr. Treatment of hypercholesterolemia by nicotinic acid. Arch Intern Med 1961;107:639–652.PubMedGoogle Scholar
  184. 184.
    Carlson LA, Oro L. Effect of treatment with nicotinic acid for one month on serum lipids in patients with different types of hyperlipidemia. Atherosclerosis 1973;18:1–9.PubMedCrossRefGoogle Scholar
  185. 185.
    Yovos JG, Patel ST, Falko JM, et al. Effects of nicotinic acid therapy on plasma lipoproteins and very low density lipoprotein apoprotein C subspecies in hyperlipoproteinemia. J Clin Endocrinol Metab 1982;54:1210–1215.PubMedCrossRefGoogle Scholar
  186. 186.
    Wahlberg G, Holmquist L, Walldius G, et al. Effects of nicotinic acid on concentrations of serum apolipoproteins B, C-I, C-IL C-III and E in hyper-lipidemic patients. Acta Med Scand. 1988;224:319–327.PubMedCrossRefGoogle Scholar
  187. 187.
    Gurakar A, Hoeg JM, Kostner G, et al. Levels of lipoprotein Lp(a) decline with neomycin and niacin treatment. Atherosclerosis 1985;57:293–301.PubMedCrossRefGoogle Scholar
  188. 188.
    Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in coronary drug project patients: long-term benefit with niacin. J Am Coll Cardiol 1986;8:1245–1255.PubMedCrossRefGoogle Scholar
  189. 189.
    Rosenhamer G, Carlson LA. Effect of combined clofibrate-nicotinic acid treatment in ischemic heart disease. Atherosclerosis 1980;37:129–138.PubMedCrossRefGoogle Scholar
  190. 190.
    Carlson LA, Rosenhamer G. Reduction of mortality in the Stockholm ischaemic heart disease secondary prevention study by combined treatment with clofibrate and nicotinic acid. Acta Med Scand 1988;223:405–418.PubMedCrossRefGoogle Scholar
  191. 191.
    Moutafis CD, Myant NB. Effects of nicotinic acid, alone or in combination with cholestyramine, on cholesterol metabolism in patients suffering from familial hyperbetalipoproteinaemia in the homozygous form. In: Gey KF, Carlson LA, eds. Metabolic Effects of Nicotinic Acid and Its Derivatives. Bern: H Huber, 1971:659–676.Google Scholar
  192. 192.
    Knopp RH, Ginsberg J, Albers JJ, et al. Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin. Metabolism 1985;34:642–650.PubMedCrossRefGoogle Scholar
  193. 193.
    Steinberg D, Parthasarathy S, Carew TE. In vivo inhibition of foam cell development by probucol in Watanabe rabbits. Cardiology 1988;62:6B–12B.CrossRefGoogle Scholar
  194. 194.
    Heel RC, Brogden RN, Speight TM, et al. Probucol: a review of its pharmacological properties and therapeutic use in patients with hypercholesterolemia. Drugs 1978;15:409–428.PubMedCrossRefGoogle Scholar
  195. 195.
    Strandberg TE, Vanhanen H, Miettinen TA. Probucol in long-term treatment of hypercholesterolemia. Gen Pharmacol 1988;19:317–320.PubMedGoogle Scholar
  196. 196.
    Buckley MM-T, Goa KL, Price AH, et al. Probucol: a reappraisal of its pharmacological properties and therapeutic use in hypercholesterolemia. Drugs 1989;37:761–800.PubMedCrossRefGoogle Scholar
  197. 197.
    Dachet C, Jacotot B, Buxtorf JC. The hypolipidemic action of probucol: drug transport and lipoprotein composition in type Ha hyperlipoproteinemia. Atherosclerosis 1985;58:261–268.PubMedCrossRefGoogle Scholar
  198. 198.
    Kesaniemi YA, Grundy SM. Influence of probucol on cholesterol and lipoprotein metabolism in man. J Lipid Res 1984;25:780–790.PubMedGoogle Scholar
  199. 199.
    Bilheimer DW. Lipoprotein fractions and receptors: a role for probucol? Am J Cardiol 1986;57:7H–15H.PubMedCrossRefGoogle Scholar
  200. 200.
    Naruszewicz M, Carew TE, Pittman RC, et al. A novel mechanism by which probucol lowers low density lipoprotein levels demonstrated in the LDL receptor-deficient rabbit. J Lipid Res 1984;25:1206–1213.PubMedGoogle Scholar
  201. 201.
    Steinberg D, Parthasarathy S, Carew TE, et al. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989;320:915–924.PubMedCrossRefGoogle Scholar
  202. 202.
    Kita T, Nagano Y, Yokode M, et al. Probucol prevents the progression of atherosclerosis in watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia. Proc Natl Acad Sci USA 1987;84:5928–5931.PubMedCrossRefGoogle Scholar
  203. 203.
    Carew TE, Schwenke DC, Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the watanabe herit¬able hyperlipidemic rabbit. Proc Natl Acad Sci USA 1987;84:7725–7729.PubMedCrossRefGoogle Scholar
  204. 204.
    Wissler RW, Vesselinovitch D. Combined effects of cholestyramine and probucol on regression of atherosclerosis in rhesus monkey aortas. AppI Pathol 1983;1:89–96.Google Scholar
  205. 205.
    Yamamoto A, Matsuzawa Y, Yokoyama S, et al. Effects of probucol on xanthomata regression in familial hypercholesterolemia. Am J Cardiol 1986;57:29H–35H.PubMedCrossRefGoogle Scholar
  206. 206.
    Yamamoto A, Hara H, Takaichi S, et al. Effect of probucol on macrophages, leading to regression of xanthomas and atheromatous vascular lesions. Am J Cardiol 1988;62:31B–36B.PubMedCrossRefGoogle Scholar
  207. 207.
    Iida H, Izumino K, Asaka M, et al. Effect of probucol on hyperlipidemia in patients with nephrotic syndrome. Nephron 1987;47:280–283.PubMedCrossRefGoogle Scholar
  208. 208.
    Jackman WM, Friday KJ, Anderson JL, et al. The long QT syndromes: a critical review, new clinical observations and a unifying hypothesis. Prog Car-diovasc Dis 1988;31:115–172.CrossRefGoogle Scholar
  209. 209.
    Davignon J. Medical management of hyperlipidemia and the role of probucol. Am J Cardiol 1986;57:22H–28H.PubMedCrossRefGoogle Scholar
  210. 210.
    Miettinen TA, Huttunen JK, Naukkarinen V, et al. Long-term use of probucol In the multifactorial primary prevention of vascular disease. Am J Cardiol 1986;57:49H–54H.PubMedCrossRefGoogle Scholar
  211. 211.
    Yokohama S, Yamamoto A, Kurasawa T. A little more information about aggravation of probucol-induced HDL-reduction by clofibrate. Atherosclerosis 1988;70:179–181.CrossRefGoogle Scholar
  212. 212.
    Gordon DJ, Probstfield JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease. Circulation 1989;79:8–15.PubMedCrossRefGoogle Scholar
  213. 213.
    Nestruck AC, Bouthillier D, Sing CF, et al. Apolipoprotein E polymorphism and plasma cholesterol response to probucol. Metabolism 1987;36:743–747.PubMedCrossRefGoogle Scholar
  214. 214.
    Anderson JL, Schroeder JS. Effects of probucol on hyperlipidemic patients with cardiac allografts. J Cardiovasc Pharmacol 1979;1:353–365.PubMedCrossRefGoogle Scholar
  215. 215.
    Walldius G, Carlson LA, Erikson U, et al. Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: probucol quantitative regression Swedish trial (PQRST): a status report. Am J Cardiol 1988;62:37B–43B.PubMedCrossRefGoogle Scholar
  216. 216.
    Witztum JL, Simmons D, Steinberg D, et al. Intensive combination drug therapy of familial hypercholesterolemia with lovastatin, probucol, and colestipol hydrochloride. Circulation 1989;79:16–28.PubMedCrossRefGoogle Scholar
  217. 217.
    Illingworth DR. Drug therapy of hypercholesterolemia. Clin Chem 1988; 34:B123–B132.PubMedGoogle Scholar
  218. 218.
    Malloy MJ, Kane JP, Kunitake ST, et al. Complementarity of colestipol, niacin and lovastatin in treatment of severe familial hypercholesterolemia. Ann Intern Med 1987;107:616–623.PubMedGoogle Scholar
  219. 219.
    Illingworth DR, Bacon S. Influence of lovastatin plus gemfibrozil on plasma lipids and lipoproteins in patients with heterozygous familial hypercholesterolemia. Circulation 1989;79:590–596.CrossRefPubMedGoogle Scholar
  220. 220.
    Dtijovne CA, Harris WS. The pharmacological treatment of dyslipidemia. Annu Rev Pharmacol Toxicol 1989;29:265–288.CrossRefGoogle Scholar
  221. 221.
    Hoeg JM, Maher MB, Bou E, et al. Normalization of plasma lipoprotein concentrations in patients with type II hyperlipoproteinemia by combined use of neomycin and niacin. Circulation 1984;70:1004–1011.CrossRefPubMedGoogle Scholar
  222. 222.
    Samuel P, Holtzman CM, Goldstein J. Long-term reduction of serum cholesterol levels of patients with atherosclerosis by small doses of neomycin. Circulation 1967;35:938–945.PubMedGoogle Scholar
  223. 223.
    Samuel P. Treatment of hypercholesterolemia with neomycin—a time for reappraisal. N Engl J Med 1979;301:595–597.PubMedCrossRefGoogle Scholar
  224. 224.
    Hoeg JM, Schaefer EJ, Romano CA, et al. Neomycin and plasma lipoproteins in type II hyperlipoproteinemia. Clin Pharmacol Ther 1984;36:555–565.PubMedCrossRefGoogle Scholar
  225. 225.
    Miettinen TA. Effects of neomycin alone and in combination with cholestyramine on serum cholesterol and fecal steroids in hypercholesterolemic subjects. J Clin Invest 1979;64:1485–1493.PubMedCrossRefGoogle Scholar
  226. 226.
    Kesaniemi YA, Grundy SM. Turnover of low density lipoproteins during inhibition of cholesterol absorption by neomycin. Arteriosclerosis 1984:4:41–48.PubMedCrossRefGoogle Scholar
  227. 227.
    Council on Drugs. Evaluation of a hypocholesterolemic agent, dextrothyrox-ine sodium (choloxin). JAMA 1969;208:1014–1015.CrossRefGoogle Scholar
  228. 228.
    Searcy RL, Hungerford DA, Low EMY. Effects of dextrothyroxine on serum lipoprotein and cholesterol levels. Curr Ther Res 1968;10:177–186.PubMedGoogle Scholar
  229. 229.
    Schwandt P, Weisweiler P. The effect of d-thyroxine on lipoprotein lipids and apolipoproteins in primary type Ila hyperlipoproteinemia. Atherosclerosis 1980;35:301–306.PubMedCrossRefGoogle Scholar
  230. 230.
    Bantle JP, Hunninghake DB, Frantz ID, et al. Comparison of effectiveness of thyrotropin-suppressive doses of d- and l-thyroxine in treatment of hypercholesterolemia. Am J Med 1984;77:475–481.PubMedCrossRefGoogle Scholar
  231. 231.
    Coronary Drug Project Research Group. The Coronary Drug Project: findings leading to further modifications of its protocol with respect to dextrothyroxine. JAMA 1972;220:996–1008.CrossRefGoogle Scholar
  232. 232.
    Tikkanen MJ, Nikkila EA, Vartiainen E. Natural estrogen as an effective treatment for type-II hyperlipoproteinaemia in postmenopausal women. Lancet 1978;2:490–491.PubMedCrossRefGoogle Scholar
  233. 233.
    Kushwaha RS, Hazzard WR, Gagne C, et al. Type III hyperlipoproteinemia: paradoxical hypolipidemic response to estrogen. Ann Intern Med 1977; 87:517–525.PubMedGoogle Scholar
  234. 234.
    Falko JM, Schonfeld G, Witztum JL, et al. Effects of estrogen therapy on apolipoprotein E in type III hyperlipoproteinemia. Metabolism 1979; 28: 1171–1177.PubMedCrossRefGoogle Scholar
  235. 235.
    Kovanen PT, Brown MS, Goldstein JL. Increased binding of low density lipoprotein to liver membranes from rats treated with 17α-ethinyl estradiol. J Biol Chem 1979;254:11367–11373.PubMedGoogle Scholar
  236. 236.
    Chao Y, Windier EE, Chen GC, et al. Hepatic catabolism of rat and human lipoproteins in rats treated with 17α-ethinyl estradiol. J Biol Chem 1979;254:11360–11366.PubMedGoogle Scholar
  237. 237.
    Coronary Drug Project Research Group. The Coronary Drug Project: initial findings leading to modifications of its research protocol. JAMA 1970; 214:1303–1313.CrossRefGoogle Scholar
  238. 238.
    Coronary Drug Project Research Group. The Coronary Drug Project: findings leading to discontinuation of the 2.5 mg/day estrogen group. JAMA 1973;226:652–657. CrossRefGoogle Scholar
  239. 239.
    Ernster VL, Bush TL, Huggins GR, et al. Benefits and risks of menopausal estrogen and/or progestin hormone use. Prev Med 1988;17:201–223.PubMedCrossRefGoogle Scholar
  240. 240.
    Barett-Connor E, Bush TL. Estrogen replacement and coronary heart disease. Cardiovasc Clin 1989;19:159–172.Google Scholar
  241. 241.
    Kane JP, and Malloy MJ. Treatment of hypercholesterolemia. Med Clin North Am 1982;66:537–550.PubMedGoogle Scholar
  242. 242.
    Lees AM, Mok HYI, Lees RS, et al. Plant sterols as cholesterol-lowering agents: clinical trials in patients with hypercholesterolemia and studies of sterol balance. Atherosclerosis 1977;28:325–338.PubMedCrossRefGoogle Scholar
  243. 243.
    Schlierf G, Oster P, Heuck CC, et al. Sitosterol in juvenile type II hyperlipoproteinemia. Atherosclerosis 1978;30:245–248.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1991

Authors and Affiliations

  • David W. Bilheimer

There are no affiliations available

Personalised recommendations