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Lipid-Lowering Drugs

An Overview of Indications and Optimum Therapeutic Use

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Summary

Drug treatment of patients with hyperlipoproteinaemia is indicated to reduce the risk of atherosclerosis in patients with increased concentrations of atherogenic lipoproteins, and to lower the plasma concentrations of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia who are at risk of abdominal pain and pancreatitis. Such therapy should be initiated only after satisfactory exclusion of secondary causes of hyperlipoproteinaemia, and should be regarded as an adjunct to rather than a substitute for appropriate dietary therapy. Drug therapy should be strongly considered in those patients with concentrations of atherogenic lipoproteins which exceed the 90th to 95th percentile for age.

In patients with increased plasma concentrations of low density lipoproteins (LDL), agents which enhance the rate of LDL catabolism (cholestyramine and colestipol) or reduce the rate of LDL synthesis [e.g. nicotinic acid (niacin)] are the ‘drugs of choice’. For those patients with concurrent hypertriglyceridaemia, nicotinic acid is the preferred initial drug, and in both patient groups combined drug therapy is often necessary to attain optimal reductions in LDL cholesterol concentrations. Clofibrate remains the ‘drug of choice’ for the rare patient with type III hyperlipoproteinaemia, whereas the newer agent gemfibrozil should be used in patients with plasma triglyceride concentrations above 1000 mg/dl who are at increased risk of abdominal pain and pancreatitis.

Although currently limited to investigational use, mevinolin and related compounds, which are specific inhibitors of the rate-limiting enzyme in cholesterol biosynthesis (HMG Co-A reductase), offer considerable promise in the therapy of patients with primary hypercholesterolaemia due to elevated levels of LDL cholesterol.

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References

  • Alberts AW, Chen J, Kuron G. Mevinolin: a highly potent competitive inhibitor of hydroxy methyl glutaryl coenzyme A reductase and a cholesterol lowering agent. Proceedings of the National Academy of Sciences (USA) 77: 3957–3961, 1980

    Article  CAS  Google Scholar 

  • Altschul R, Hoeffer A, Stephen JD. Influence of nicotinic acid on serum cholesterol in man. Archives of Biochemistry and Biophysics 54: 558–559, 1955

    Article  PubMed  CAS  Google Scholar 

  • Baker SG, Joffe BI, Mendelsohn D, Seftel HC. Treatment of homozygous familial hypercholesterolaemia with probucol. South African Medical Journal 62: 7–11, 1982

    PubMed  CAS  Google Scholar 

  • Bantle JP, Oppenheimer JH, Schwartz HL, Hunninghake DB, Probstfield JL, et al. TSH response to TRH in euthyroid hypercholesterolemic patients treated with graded doses of dextrothyroxine. Metabolism 30: 63–68, 1981

    Article  PubMed  CAS  Google Scholar 

  • Bilheimer DW, Grundy SM, Brown MS, Goldstein JL. Mevinolin and colestipol stimulate receptor mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proceedings of the National Academy of Sciences (USA) 80: 4124–4128, 1983

    Article  CAS  Google Scholar 

  • Boberg J, Boberg M, Gross R. The effect of treatment with clofibrate on hepatic triglyceride and lipoprotein lipase activities of post heparin plasma in male patients with hyperlipidemia. Atherosclerosis 27: 499–503, 1977

    Article  PubMed  CAS  Google Scholar 

  • Brensike JF, Levy RI, Kelsy SF. Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI type II coronary intervention study. Circulation 69: 313–324, 1984

    Article  PubMed  CAS  Google Scholar 

  • Brown WV, Goldberg IJ, Ginsberg HN. Treatment of common lipoprotein disorders. Progress Cardiovascular Diseases 27: 1–21, 1984

    Article  CAS  Google Scholar 

  • Brown MS, Goldstein JL. Drugs used in the treatment of hyperlipoproteinemias. In Gilman et al. (Eds) The pharmacological basis of therapeutics, 7th ed., pp. 827–845, McMillan, New York, 1985

    Google Scholar 

  • Carlson LA. Effect of nicotinic acid on serum lipids and lipoproteins. In Carlson & Olsson (Eds), Treatment of hyperlipoproteinemia, pp. 115–119, Raven Press, New York, 1984

    Google Scholar 

  • Committee of Principal Investigators. A cooperative trial in the primary prevention of ischemic heart disease using clofibrate. British Heart Journal 40: 1069–1118, 1978

    Article  Google Scholar 

  • Committee of Principal Investigators. WHO cooperative trial on primary prevention of ischemic heart disease using clofibrate to lower cholesterol: final mortality follow-up. Lancet 2: 600–605, 1984

    Google Scholar 

  • Consensus Conference. Lowering blood cholesterol to prevent heart disease. Journal of the American Medical Association 253: 2080–2086, 1985

    Article  Google Scholar 

  • Coronary Drug Project. Findings leading to further modifications of its protocol with respect to dextrothyroxine. Journal of the American Medical Association 220: 996–1002, 1972

    Article  Google Scholar 

  • Coronary Drug Project. Clofibrate and niacin in coronary heart disease. Journal of the American Medical Association 231: 360–365, 1975

    Article  Google Scholar 

  • Dujovne CA, Krehbiel P, Decoursey S, Jackson B, Chernoff SB, et al. Probucol with colestipol in the treatment of hypercholesterolemia. Annals of Internal Medicine 100: 477–483, 1983

    Google Scholar 

  • Endo A, Tsujita Y, Kuroda M, Tanazawa K. Inhibition of cholesterol synthesis in vivo by ML236B, a competitive inhibitor of 3-hydroxy 3-methyl glutaryl coenzyme A reductase. European Journal of Biochemistry 87: 313–319, 1977

    Google Scholar 

  • Glueck CJ. Effects of oxandrolone on plasma triglycerides and postheparin lipolytic activity in patients with types III, IV and V familial hyperlipoproteinemia. Metabolism 20: 691–702, 1971

    Article  PubMed  CAS  Google Scholar 

  • Glueck CJ. Pediatric primary prevention of atherosclerosis. New England Journal of Medicine 314: 175–177, 1986

    Article  PubMed  CAS  Google Scholar 

  • Glueck CJ, Levy RI, Fredrickson DS. Norethindrone acetate, post heparin lipolytic activity and plasma triglycerides in familial types I, III, IV and V hyperlipoproteinemia: studies in 26 patients and 5 normal patients. Annals of Internal Medicine 75: 345–352, 1971

    PubMed  CAS  Google Scholar 

  • Goldstein JL, Brown MS. Familial hypercholesterolemia. In Stanbury et al. (Eds) The metabolic basis of inherited disease, 5th ed., pp. 672–713, McGraw Hill, New York, 1983

    Google Scholar 

  • Goldstein JL, Schrott HG, Hazard WR. Hyperlipidemia in coronary heart disease: genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder combined hyperlipidemia. Journal of Clinical Investigation 52: 1544–1568, 1973

    Article  PubMed  CAS  Google Scholar 

  • Gordon T, Castelli WP, Hjortland MC, Kannel WM. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. American Journal of Medicine 12: 707–714, 1977

    Article  Google Scholar 

  • Grundy SM, Bilheimer DW. Inhibition of 3-hydroxy 3-methyl glutaryl CoA reductase by mevinolin in familial hypercholesterolemia heterozygotes: effects on cholesterol balance. Proceedings of the National Academy of Sciences (USA) 81: 2538–2542, 1984

    Article  CAS  Google Scholar 

  • Grundy SM, Mok HYI, Zack L, Berman M. The influence of nicotinic acid on metabolism of cholesterol and triglycerides in man. Journal of Lipid Research 22: 24–36, 1981

    PubMed  CAS  Google Scholar 

  • Grundy SM, Vega GL. Influence of mevinolin on metabolism of low density lipoproteine in primary moderate hypercholesterolemia. Journal of Lipid Research 26: 1464–1475, 1985

    PubMed  CAS  Google Scholar 

  • Grundy SM, Vega GL, Bilheimer DW. Influence of combined therapy with mevinolin and interruption of bile acid reabsorption on low density lipoproteine in heterozygous familial hypercholesterolemia. Annals of Internal Medicine 103: 339–343, 1985

    PubMed  CAS  Google Scholar 

  • Gugler R. Clinical pharmacokinetics of hypolipidaemic drugs. Clinical Pharmacokinetics 3: 425–439, 1978

    Article  PubMed  CAS  Google Scholar 

  • Hoeg JM, Gregg RE, Brewer Jr HB. An approach to the management of hyperlipoproteinemia. Journal of the American Medical Association 255: 512–521, 1986

    Article  PubMed  CAS  Google Scholar 

  • Hoeg JM, Mather MB, Bou E, Zeck LA, Bailey KR, et al. Normalisation of plasma lipoprotein concentrations in patients with type II hyperlipoproteinemia by combined use of neomycin and niacin. Circulation 70: 1004–1011, 1984a

    Article  PubMed  CAS  Google Scholar 

  • Hoeg JM, Schaefer EJ, Romano CA, Bou E, Pikus AM, et al. Neomycin and plasma lipoproteins in type II hyperlipoproteinemia. Clinical Pharmacology and Therapeutics 36: 555–559, 1984b

    Article  PubMed  CAS  Google Scholar 

  • Illingworth DR. Mevinolin plus colestipol in therapy for severe heterozygous familial hypercholesterolemia. Annals of Internal Medicine 101: 598–604, 1984

    PubMed  CAS  Google Scholar 

  • Illingworth DR, Connor WE. Hyperlipidemia and coronary heart disease. In Connor & Bristow (Eds), Coronary heart disease, prevention, complications and treatment, pp. 21–42, Lippincott, 1985

    Google Scholar 

  • Illingworth DR, Connor WE. Hypercholesterolemia persisting after distal ileal bypass: response to mevinolin. Annals of Internal Medicine 100: 850–851, 1984

    PubMed  CAS  Google Scholar 

  • Illingworth DR, Corbin D. Influence of mevinolin on the adrenocortical response to corticotropin in heterozygous familial hypercholesterolemia. Proceedings of the National Academy of Sciences (USA) 82: 6291–6295, 1985

    Article  CAS  Google Scholar 

  • Illingworth DR, Olsen GD, Cook SF, Connor WE. Ciprofibrate in the therapy of type II hypercholesterolemia: a double blind trial. Atherosclerosis 44: 211–221, 1982

    Article  PubMed  CAS  Google Scholar 

  • Illingworth DR, Phillipson BE, Rapp JH, Connor WE. Colestipol plus nicotinic acid in treatment of heterozygous familial hypercholesterolemia. Lancet 1: 296–298, 1981

    Article  PubMed  CAS  Google Scholar 

  • Illingworth DR, Sexton GJ. Hypocholesterolemic effects of mevinolin in patients with heterozygous familial hypercholesterolemia. Journal of Clinical Investigation 74: 1972–1978, 1984

    Article  PubMed  CAS  Google Scholar 

  • Janus ED, Nicol AM, Turner PL, Lewis B. Kinetic basis of the primary hyperlipoproteinemias: studies of apolipoprotein B turnover in genetically defined subjects. European Journal of Clinical Investigation 10: 161–168, 1980

    Article  PubMed  CAS  Google Scholar 

  • Kane JP, Malloy MJ. Treatment of hypercholesterolemia. Medical Clinics of North America 66: 537–550, 1982

    PubMed  CAS  Google Scholar 

  • Kane JP, Malloy MJ, Tun P, Phillips NR, Freeman D, et al. Normalization of low density lipoprotein levels in heterozygous familial hypercholesterolemia with a combined drug regimen. New England Journal of Medicine 304: 251–258, 1981

    Article  PubMed  CAS  Google Scholar 

  • Kesaniemi YA, Grundy SM. Influence of gemfibrozil and clofibrate on metabolism of cholesterol and plasma triglycerides in man. Journal of the American Medical Association 251: 2241–2247, 1984

    Article  PubMed  CAS  Google Scholar 

  • Knopp RH, Ginsberg J, Albers JJ, Hoff C, Oglivie JT, et al. Contrasting effects of unmodified and time released forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin. Metabolism 34: 642–647, 1985

    Article  PubMed  CAS  Google Scholar 

  • Kuo PT, Kostis JB, Moreyra A, Hayes JA. Familial type II hyperlipoproteinemia with coronary heart disease: effects of colestipol plus nicotinic acid. Chest 79: 286–291, 1981

    Article  PubMed  CAS  Google Scholar 

  • Langer T, Levy RI. Acute muscular syndrome associated with administration of clofibrate. New England Journal of Medicine 279: 856–858, 1968

    Article  PubMed  CAS  Google Scholar 

  • Leaf DA, Connor WE, Illingworth DR, Bacon SP. The hypolipidaemic effects of gemfibrozil in type V hyperlipidaemia. Submitted for publication, 1986

  • Lehrman MA, Goldstein JL, Brown MS, Russell DW, Schneider WJ. Internalization defective LDL receptors produced by genes with nonsense and frame shift mutations that truncate the cytoplasmic domain. Cell 41: 735–743, 1985

    Article  PubMed  CAS  Google Scholar 

  • Leiss O, Bergmann K, Gnasso A, Augustin J. Effect of gemfibrozil on biliary lipid metabolism in normolipidaemic subjects. Metabolism 34: 74–82, 1985

    Article  PubMed  CAS  Google Scholar 

  • Lewis JE. Clinical use of gemfibrozil: a controlled multicentre trial. Practical Cardiology 9: 99–118, 1983

    Google Scholar 

  • Lipid Research Clinics Population Studies Data Book, Vol. 1, NIH Publication No. 80-1527, Department of Health and Human Services, Bethesda, 1980

  • Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results. 1. Reduction in incidence in coronary heart disease. Journal of the American Medical Association 251: 351–364, 1984a

    Article  Google Scholar 

  • Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results. 2. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. Journal of the American Medical Association 251: 365–374, 1984b

    Article  Google Scholar 

  • Mahley RW, Angelin B. Type III hyperlipoproteinemia: recent insights into the genetic defect of familial dysbetalipoproteinemia. Advances in Internal Medicine 29: 385–441, 1984

    PubMed  CAS  Google Scholar 

  • Malmendier CL, Delcroix C. Effects of fenofibrate on high and low density lipoprotein metabolism in heterozygous familial hypercholesterolemia. Atherosclerosis 55: 161–169, 1985

    Article  PubMed  CAS  Google Scholar 

  • Mellies MJ, Gartside PS, Galtfeleter L, Glueck GJ. Effect of probucol on plasma cholesterol high and low density lipoprotein cholesterol and apolipoprotein A1 and A2 in adults with primary familial hypercholesterolemia. Metabolism 29: 956–964, 1980

    Article  PubMed  CAS  Google Scholar 

  • Miettinen TA. Effects of neomycin alone and in combination with cholestyramine on serum cholesterol and fecal steroids in hypercholesterolemic subjects. Journal of Clinical Investigation 64: 1485–1492, 1979

    Article  PubMed  CAS  Google Scholar 

  • Miettinen TA, Huttenen LK, Kusi T. Effect of probucol on the activity of post heparin plasma lipoprotein lipase and hepatic lipase. Clinica Chimica Acta 113: 59–64, 1981

    Article  CAS  Google Scholar 

  • Mordasani R, Reisen W, Oster P. Reduced LDL and increased HDL apoproteins in patients with hypercholesterolemia under treatment with bezafibrate. Atherosclerosis 40: 153–162, 1981

    Article  Google Scholar 

  • Nestel PJ, Billington T. Effects of probucol on low density lipoprotein removal and high density lipoprotein synthesis. Atherosclerosis 38: 203–209, 1981

    Article  PubMed  CAS  Google Scholar 

  • Nicoll A, Miller NE, Lewis B. High density lipoprotein metabolism. Advances in Lipid Research 17: 54–106, 1980

    Google Scholar 

  • Olsson AG, Carlson LA, Anggard E, Ciabattioni G. Prostacyclin production augmented in the short term by nicotinic acid. Lancet 2: 565–567, 1983

    Article  PubMed  CAS  Google Scholar 

  • Phillipson BE, Rothrock DW, Connor WE, Harris WS, Illingworth DR. The reduction of plasma lipids, lipoproteins and apoproteins in hypertriglyceridemic patients by dietary fish oils. New England Journal of Medicine 312: 1210–1216, 1985

    Article  PubMed  CAS  Google Scholar 

  • Rossner S, Oro L. Fenofibrate therapy of hyperlipoproteinemia — a dose response study and comparison with clofibrate. Atherosclerosis 38: 273–282, 1981

    Article  PubMed  CAS  Google Scholar 

  • Sabesin SM. Cholestatic lipoproteins: their pathogenesis and significance. Gastroenterology 83: 704–707, 1982

    PubMed  CAS  Google Scholar 

  • Saku K, Gartside PS, Hynd BA, Kashyap ML. Mechanism of action of gemfibrozil on lipoprotein metabolism. Journal of Clinical Investigation 75: 1702–1712, 1985

    Article  PubMed  CAS  Google Scholar 

  • Samuel P. Treatment of hypercholesterolemia with neomycin: a time for reappraisal. New England Journal of Medicine 301: 595–597, 1979

    Article  PubMed  CAS  Google Scholar 

  • Schaefer EJ, Levy RI. Pathogenesis and management of lipoprotein disorders. New England Journal of Medicine 312: 1300–1310, 1985

    Article  PubMed  CAS  Google Scholar 

  • Schonfeld G. Disorders of lipid transport, update 1983. Progress in Cardiovascular Disease 26: 89–108, 1983

    Article  CAS  Google Scholar 

  • Shepherd J, Packard CJ, Bicker S, Laurie TDV, Morgan HG. Cholestyramine promotes receptor mediated low density lipoprotein catabolism. New England Journal of Medicine 302: 1219–1222, 1980

    Article  PubMed  CAS  Google Scholar 

  • Stewart JM, Packard CJ, Lormer AR, Boag DE, Shepherd J. Effects of bezafibrate on receptor mediated and receptor independent low density lipoprotein catabolism in type II hyperlipoproteinemic subjects. Atherosclerosis 44: 355–368, 1982

    Article  PubMed  CAS  Google Scholar 

  • Thompson GR, Soutar AV, Spengel FA. Defects of receptor mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. Proceedings of the National Academy of Sciences (USA) 768: 2591–2595, 1981

    Article  Google Scholar 

  • Vega GL, Grundy SM. Gemfibrozil therapy in primary hypertriglyceridemia associated with coronary heart disease: effects on metabolism of low density lipoproteins. Journal of the American Medical Association 253: 2398–2404, 1985

    Article  PubMed  CAS  Google Scholar 

  • Wilson DE, Lees RS. Metabolic relationships among the plasma lipoproteins. Reciprocal changes in the concentrations of very low and low density lipoproteins in man. Journal of Clinical Investigation 51: 1051–1060, 1972

    Article  PubMed  CAS  Google Scholar 

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  1. Division of Endocrinology, Metabolism and Clinical Nutrition, Department of Medicine, Oregon Health Sciences University, Portland, OR, 97201, USA

    D. Roger Illingworth

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Illingworth, D.R. Lipid-Lowering Drugs. Drugs 33, 259–279 (1987). https://doi.org/10.2165/00003495-198733030-00003

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