Advertisement

The discovery and development of HMG-CoA reductase inhibitors.

Open AccessPublished:November 01, 1992DOI:https://doi.org/10.1016/S0022-2275(20)41379-3
      This paper is only available as a PDF. To read, Please Download here.

      REFERENCES

        • Keys A
        Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease. Harvard University Press, Cambridge, MA1980: 1-381
        • Lipid Research Clinics Program
        The Lipid Research Clinics Coronary Primary Prevention Trial Results. 1. Reduction in the incidence of coronary heart disease.
        JAMA. 1988; 251: 351-364
        • Endo A.
        • Kuroda M.
        • Tsujita Y.
        ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogen-esis produced by Penicillium citrinum.
        J. Antibiot. (Japan). 1976; 29: 1346-1348
        • Endo A.
        • Kuroda M.
        • Tanzawa K.
        Competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by ML-236A and ML-236B, fungal metabolites, having hypocholesterolemic activity.
        FEBS Lett. 1976; 72: 323-326
        • Kaneko I.
        • Hazama-Shimada Y.
        • Endo A.
        Inhibitory effects on lipid metabolism in cultured cells of ML-236B, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
        Eur. J. Biochem. 1978; 87: 313-321
        • Tsujita Y.
        • Kuroda M.
        • Tanzawa K.
        • Kitano N.
        • Endo A.
        Hypolipidemic effects in dogs of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
        Atherosclerosis. 1979; 32: 307-313
        • Kuroda M.
        • Tsujita Y.
        • Tanzawa K.
        • Endo A.
        Hypolipidemic effects in monkeys of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
        Lipids. 1979; 14: 585-589
        • Yamamoto A.
        • Sudo H.
        • Endo A.
        Therapeutic effects of ML-236B in primary hypercholesterolemia.
        Atherosclerosis. 1980; 35: 259-266
        • Grundy S.M.
        HMG-CoA reductase inhibitors for treatment of hypercholesterolemia.
        N. Engl. J. Med. 1988; 319: 24-33
        • Hunninghake D.B.
        HMG-CoA reductase inhibitors.
        Curr. Opin. Lipidol. 1992; 3: 22-28
        • Brown G.
        • Albers J.J.
        • Fisher L.D.
        • Schaffer S.M.
        • Lin J.T.
        • Kaplan C.
        • Zhao X.Q.
        • Bisson B.D.
        • Fitz-patrick V.F.
        • Dodge H.T.
        Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B..
        N. Engl. J. Med. 1990; 323: 1289-1298
        • Altschul R.
        • Hoffer A.
        • Stephen J.D.
        Influence of nicotinic acid on serum cholesterol in man.
        Arch. Biochem. Biopkys. 1955; 54: 558-559
        • Tennet D.M.
        • Siegel H.
        • Zanetti M.E.
        • Kuron G.W.
        • Ott W.H.
        • Walf F.J.
        Plasma cholesterol lowering action of bile acid binding polymers in experimental animals.
        J. Lipid Res. 1960; 1: 469-473
        • Thorp J.M.
        • Waring W.S.
        Modification of metabolism and distribution of lipids by ethyl chlo-rophenoxyisobutyrate.
        Nature. 1962; 194: 948-949
        • Goldsmith G.A.
        • Hamilton J.G.
        • Miller O.N.
        Lowering of serum lipid concentrations. Mechanisms used by unsaturated fats, nicotinic acid and neomycin: excretion of sterols and bile acids.
        Arch. Intern. Med. 1960; 105: 512-517
        • Pollak O.J.
        Reduction of blood cholesterol in man.
        Circulation. 1953; 7: 702-706
        • Hollander W.
        • Chobanian A.
        Effects of an inhibitor of cholesterol biosynthesis, triparanol (MER-29), in subjects with and without coronary artery disease.
        Boston Med. Quart. 1959; 10: 37-44
        • Starr P.
        • Roen P.
        • Freibrun J.L.
        • Schleissner L.A.
        Reduction of serum cholesterol by sodium D-thyroxine.
        A.M.A. Arch. Intern. Med. 1960; 105: 830-842
        • Taupitz A.
        • Otaguro K.
        The effects of estrogens on the serum cholesterol of male rats.
        Symp. Deut. Ges. En-dokrinol. 1959; : 430-432
        • AMA Department of Drugs
        AMA Drug Evaluations. 3rd ed. PSG Publishing Company, Littleton, MA1977: 153-174
        • Laughlin R.C.
        • Carey T.F.
        Cataracts in patients treated with triparanol.
        JAMA. 1962; 181: 339-340
        • Dietschy J.M.
        • Wilson J.D.
        Regulation of cholesterol metabolism.
        N. Engl. J. Med. 1970; 282 (1179-1183, 1241–1249): 1128-1138
        • Siperstein M.D.
        Regulation of cholesterol biosynthesis in normal and malignant tissues.
        Curr. Top. Cell. Regul. 1970; 2: 65-100
        • Dietschy J.M.
        • Siperstein M.D.
        Effect of cholesterol feeding and fasting on sterol synthesis in seventeen tissues of the rat.
        J. Lipid Res. 1967; 8: 97-104
        • Dietschy J.M.
        • Wilson J.D.
        Cholesterol synthesis in the squirrel monkey: relative rates of synthesis in various tissues and mechanisms of control.
        J. Clin. Invest. 1968; 47: 166-174
        • Siperstein M.D.
        • Fagan V.M.
        Feedback control of mevalonate synthesis by dietary cholesterol.
        J. Biol. Chem. 1966; 241: 602-609
        • Goldfarb S.
        • Pitot H.C.
        Improved assay of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
        J. Lipid Res. 1971; 12: 512-515
        • Knauss H.J.
        • Porter J.W.
        • Watson G.
        The biosynthesis of mevalonic acid from 1-14C-acetate by rat liver enzyme system.
        J. Biol. Chem. 1959; 234: 2835-2840
        • Endo A.
        • Kuroda M.
        Citrinin, an inhibitor of cholesterol synthesis.
        J. Antibiot. (Japan). 1976; 29: 841-843
        • Tanzawa K.
        • Kuroda M.
        • Endo A.
        Time-dependent, irreversible inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase by the antibiotic citrinin.
        Biochim. Biophys. Acta. 1977; 488: 97-101
        • Brown A.G.
        • Smale T.C.
        • King T.J.
        • Hasenkamp R.
        • Thompson R.H.
        Crystal and molecular structure of compactin, a new antifungal metabolite from Penicillium brevicompactum.
        J. Chem. Soc. Perkin I. 1976; : 1165-1170
        • Endo A
        Compactin (ML-236B) and related compounds as potential cholesterol-lowering agents that inhibit HMG-CoA reductase.
        J. Med. Chem. 1985; 28: 401-405
        • Tanzawa K.
        • Endo A.
        Kinetic analysis of the reaction catalyzed by rat-liver 3-hydroxy-3-methylglutaryl coenzyme A reductase using two specific inhibitors.
        Eur. J. Biochem. 1979; 98: 195-201
        • Abeles R.H.
        • Nakamura H.
        Mode of interaction of β-hydroxy-β-methylglutaryl coenzyme A reductase with strong binding inhibitors.Compactin and related compounds.
        Biochemistry. 1985; 24: 1364-1376
        • Sato A.
        • Ogiso A.
        • Noguchi H.
        • Mitsui S.
        • Kaneko I.
        • Shimada Y.
        Mevalonolactone derivatives as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
        Chem. Pharm. Bull. (Japan). 1980; 28: 1509-1525
        • Endo A
        Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-meythylglutaryl coenzyme A reductase.
        J. Antibiot. (Japan). 1979; 33: 334-336
        • Alberts A.W.
        • Chen J.
        • Curon G.
        • Hunt V.
        • Huff J.
        • Hoffman C.
        • Rothrock J.
        • Lopez M.
        • Joshau H.
        • Harris E.
        • Patchett A.
        • Monaghan R.
        • Currie S.
        • Stapley E.
        • Albers-Schönberg G.
        • Hensens O.
        • Hirshfield J.
        • Hoogsteen K.
        • Liesch J.
        • Springer J.
        Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and cholesterol-lowering agent.
        Proc. Natl. Acad. Sci. USA. 1980; 77: 3957-3961
        • Yamashita H.
        • Tsubokawa S.
        • Endo A.
        Microbial hydroxylation of compactin (ML-236B) and monacolin K..
        J. Antibiot. (Japan). 1985; 38: 605-609
        • Brown M.S.
        • Dana S.E.
        • Goldstein J.L.
        Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts by lipoproteins.
        Proc. Natl. Acad. Sci. USA. 1973; 70: 2162-2166
        • Brown M.S.
        • Goldstein J.L.
        Familial hypercholesterolemia: defective binding of lipoproteins to cultured fibroblasts associated with impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.
        Proc. Natl. Acad. Sci. USA. 1974; 71: 788-792
        • Goldstein J.L.
        • Brown M.S.
        Lipoprotein receptors, cholesterol metabolism, and atherosclerosis.
        Arch. Pathol. 1975; 99: 181-184
        • Brown M.S.
        • Goldstein J.L.
        Receptor-mediated control of cholesterol metabolism.
        Science. 1976; 191: 150-154
        • Brown M.S.
        • Faust J.R.
        • Goldstein J.L.
        • Kaneko I.
        • Endo A.
        Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase.
        J. Biol. Chem. 1978; 253: 1121-1128
        • Doi I.
        • Endo A.
        Specific inhibition of des-mosterol synthesis by ML-236B in mouse LM cells grown in suspension in a lipid-free medium.
        J. Med. Sci. Biol. (Japan). 1978; 31: 225-233
        • Endo A
        Specific nonsterol inhibitors of HMG-CoA reductase.
        in: Preiss B. Regulation of HMG-CoA reductase. Academic Press, New York, NY1985: 49-78
        • Quesney-Huneeus V.
        • Wiley M.H.
        • Siperstein M.D.
        Essential role for mevalonate synthesis in DNA replication.
        Proc. Natl. Acad. Sci. USA. 1979; 76: 5056-5060
        • Habenicht A.J.R.
        • Glomset J.A.
        • Ross R.
        Relation of cholesterol and mevalonic acid to the cell cycle in smooth muscle and Swiss 3T3 cells stimulated to divide by platelet-derived growth factor.
        J. Biol. Chan. 1980; 255: 5134-5140
        • Schmidt R.A.
        • Glomset J.A.
        • Wight T.N.
        • Ha-henicht A.J.R.
        • Ross R.
        A study of the influence of mevalonic acid and its metabolites on the morphology of Swiss 3T3 cells.
        J. Cell Biol. 1982; 95: 144-153
        • Schmidt R.A.
        • Schneider C.J.
        • Glomset J.A.
        Evidence for post-translational incorporation of a product of mevalonic acid into Swiss 3T3 cell proteins.
        J. Biol. Chem. 1984; 256: 10175-10180
        • Hancock J.F.
        • Magee A.I.
        • Childs J.E.
        • Marshall C.J.
        All ras proteins are polyisoprenylated but only some are palmitoylated.
        Cell. 1989; 57: 1167-1177
        • Schafer R.W.
        • Kim R.
        • Sterne R.
        • Thorner J.
        • Kim S.H.
        • Rine J.
        Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans.
        Science. 1989; 245: 379-385
        • Wolda S.L.
        • Glomset J.A.
        Evidence for modification of lamin B by a product of mevalonic acid.
        J. Biol. Chem. 1988; 263: 5997-6000
        • Beck L.A.
        • Hosick T.J.
        • Sinensky M.
        Incorporation of a product of mevalonic acid metabolism into proteins of Chinese hamster ovary cell nuclei.
        J. Cell Biol. 1988; 107: 1307-1316
        • Gibbs J.B.
        • Marshall M.S.
        The ras oncogenes —an important regulatory element in lower eu-karyotic organisms.
        Micro. Rev. 1989; 53: 171-185
        • Goldstein J.L.
        • Brown M.S.
        Regulation of the mevalonate pathway.
        Nature. 1990; 343: 425-430
        • Rine J.
        • Kim S.H.
        Role for isoprenoid lipids in the localization and function of an oncoprotein.
        New Biol. 1990; 2: 219-226
        • Glomset J.A.
        • Gelb M.
        • Farnsworth C.
        The prenylation of proteins.
        Curr. Opin. Lipidol. 1992; 2: 118-124
        • Chin D.J.
        • Luskey K.L.
        • Andreson R.G.W.
        • Faust J.R.
        • Goldstein J.L.
        • Brown M.S.
        Appearance of crystalloid endoplasmic reticulum in compactin-resistant Chinese hamster cells with a 500-fold increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase.
        Proc. Natl. Acad. Sci. USA. 1982; 79: 1185-1189
        • Luskey K.L.
        • Faust J.R.
        • Chin D.J.
        • Brown M.S.
        • Goldstein J.L.
        Amplification of the gene for 3-hydroxy-3-methylglutaryl coenzyme A reductase, but not for the 53-kDa protein, in UT-1 cells.
        J. Biol. Chem. 1983; 258: 8462-8469
        • Chin D.J.
        • Luskey K.L.
        • Faust J.L.
        • MacDonald R.J.
        • Brown M.S.
        • Goldstein J.R.
        Molecular cloning of 3-hydroxy-3-methylglutaryl coenzyme A reductase and evidence for regulation of its mRNA.
        Proc. Natl. Acad. Sci. USA. 1982; 79: 7704-7708
        • Chin D.J.
        • Gil G.
        • Russell D.W.
        • Liscum L.
        • Luskey K.L.
        • Basu S.K.
        • Okayama H.
        • Berg P.
        • Goldstein J.L.
        • Brown M.S.
        Nuclotide sequence of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a glycoprotein of endoplasmic reticulum.
        Nature. 1984; 308: 613-617
        • Liscum L.
        • Luskey K.L.
        • Chin D.J.
        • Ho Y.K.
        • Goldstein J.L.
        • Brown M.S.
        Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its mRNA in rat liver as studied with a monoclonal antibody and a cDNA probe.
        J. Biol. Chem. 1983; 258: 8450-8455
        • Liscum L.
        • Finer-Moore J.
        • Stroud R.M.
        • Luskey K.L.
        • Brown M.S.
        • Goldstein J.L.
        Domain structure of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a glycoprotein of the endoplasmic reticulum.
        J. Biol. Chem. 1985; 260: 522-530
        • Endo A.
        • Tsujita Y.
        • Kuroda M.
        • Tanzawa K.
        Effects of ML-236B on cholesterol metabolism: lack of hypocholesterolemic activity in normal animals.
        Biochim. Biophys. Acta. 1979; 575: 266-276
        • Endo A.
        • Tsujita Y.
        • Kuroda M.
        • Tanzawa K.
        Inhibition of cholesterol synthesis in vitro and in vivo by ML-236A and ML-236B, competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
        Eur. J. Biochem. 1977; 77: 31-36
        • Kellner A.
        • Correll J.W.
        • Ladd A.T.
        The influence of intravenously administered surface active agents on the development of experimental atherosclerosis in rabbits.
        J. Exp. Med. 1951; 93: 385-398
        • Bucher N.L.R.
        • McGarrahan K.
        • Gould E.
        • Loud A.V.
        Cholesterol biosynthesis in preparation of liver from normal, fasting, x-irradiated, cholesterol-fed, Triton or Δ4-cholesten-3-one-treated rats.
        J. Biol. Chem. 1962; 243: 262-267
        • Kandutsch A.A.
        • Saucier S.E.
        Prevention of cyclic and Triton-induced increase in hydroxymethyl-glutaryl coenzyme A reductase and sterol synthesis by puromycin.
        J. Biol. Chem. 1969; 244: 2299-2305
        • Byers S.O.
        • Friedman M.
        • Sugiyama T.
        Triton hypercholesterolemia: cause or consequence of augmented cholesterol synthesis.
        Am. J. Physiol. 1963; 204: 1100-1102
        • Kuroda M.
        • Tanzawa K.
        • Tsujita Y.
        • Endo A.
        Mechanism for elevation of hepatic cholesterol synthesis and serum cholesterol levels in Triton WR-1339-induced hyperlipidemia.
        Biochim. Biophys. Acta. 1977; 489: 119-125
        • Endo A.
        • Kitano N.
        • Fujii S.
        Effects of ML-236B, a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase, on cholesterol metabolism.
        Adv. Exp. Med. Biol. 1978; 109 (Abstract.): 376
        • Yamamoto A.
        • Endo A.
        • Kitano Y
        • Okada A.
        • Ishikawa K.
        • Kuroshima T.
        • Kaneko I.
        Two Japanese kindreds of familial hypercholesterolemia including homozygous cases. A report of cases, and studies on serum lipoproteins and enzymes.
        Jpn. J. Med. 1978; 17: 230-239
        • Shigematsu H.
        • Hata Y.
        • Yamamoto M.
        • Oikawa T.
        • Yamauchi Y.
        • Nakaya N.
        • Goto Y.
        Treatment of hypercholesterolemia with an HMG-CoA reductase inhibitor (CS-500). I. Phase I study in normal subjects.
        Geriat. Med. (Japan). 1979; 17: 1564-1570
        • Hata Y.
        • Shigematsu H.
        • Oikawa T.
        • Yamamoto M.
        • Yamauchi Y.
        • Goto Y.
        Treatment of hypercholesterolemia with an HMG-CoA reductase inhibitor (CS-500).II. Determination of unit weight effect and daily doses by an integration method and observation of safety in initial stage.
        Geriat. Med. (Japan). 1980; 18: 104-112
        • Mabuchi H.
        • Haba T.
        • Tatami R.
        • Miyamoto S.
        • Sakai Y.
        • Wakasugi T
        • Watanabe A.
        • Koizumi J.
        • Takeda R.
        Effects of an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase on serum lipoproteins and ubiquinone-10 levels in patients with familial hyper-cholesterolemia.
        N. Engl. J. Med. 1981; 305: 478-482
        • Mabuchi H.
        • Sakai T.
        • Sakai Y.
        • Yoshimura A.
        • Watanabe A.
        • Wakasugi T.
        • Watanabe A.
        • Koizumi J.
        • Takeda R.
        Reduction of serum cholesterol in heterozygous patients with familial hypercholesterolemia: additive effects of compactin and cholestyramine.
        N. Engl. J. Med. 1983; 308: 609-613
        • Yamamoto A.
        • Yamamura T.
        • Yokoyama S.
        • Sudo H.
        • Matsuzawa Y.
        Combined drug therapy — cholestyramine and compactin —for familial hypercholesterolemia.
        Int. J. Clin. Pharmacol. Ther. Toxicol. 1984; 22: 493-497
        • Kovanen P.T.
        • Bilheimer D.W.
        • Goldstein J.L.
        • Jaramillo J.J.
        • Brown M.S.
        Regulatory role for hepatic low density lipoprotein receptors in vivo in the dog.
        Proc. Natl. Acad. Sci. USA. 1981; 78: 1194-1198
        • Bilheimer D.W.
        • Grundy S.M.
        • Brown M.S.
        • Goldstein J.L.
        Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heter-ozygotes.
        Proc. Natl. Acad. Sci. USA. 1983; 80: 4124-4128
        • Uauy R.
        • Vega G.L.
        • Grundy S.M.
        • Bilheimer D.W.
        Lovastatin therapy in receptor-negative homozygous familial hypercholesterolemia: lack of effect on low-density lipoprotein concentration or turnover.
        J. Pediatr. 1988; 113: 383-392
        • Goldstein J.L.
        • Brown M.S.
        The low-density lipoprotein pathway and its relation to atherosclerosis.
        Annu. Rev. Biochem. 1977; 46: 897-930
        • Ma P.T.S.
        • Gil G.
        • Südhof T.C.
        • Bilheimer D.W.
        • Goldstein J.L.
        • Brown M.S.
        Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits.
        Proc. Natl. Acad Sci. USA. 1986; 83: 8370-8374
        • Grundy S.M.
        • Vega G.L.
        Influence of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia.
        J. Lipid Res. 1985; 26: 1464-1475
        • Grundy S.M.
        • Bilheimer D.W.
        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
        • Parker T.S.
        • McNamara D.J.
        • Brown C.D.
        • Kolb R.
        • Ahrens Jr., E.H.
        • Alberts A.W.
        • Tobert J.
        • Chen J.
        • De Schepper P.J.
        Plasma mevalonate as a measure of cholesterol synthesis in man.
        J. Clin. Invest. 1984; 74: 795-804
        • Tobert J.A.
        • Bell G.D.
        • Birtwell J.
        • James I.
        • Kukovetz W.R.
        • Pryor J.S.
        • Buntinx A.
        • Holmes I.B.
        • Chao Y.S.
        • Bolognese J.A.
        Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, in healthy volunteers.
        J. Clin. Invest. 1982; 69: 913-919
        • Illlingworth D.R.
        • Sexton G.J.
        Hypocholestero-lemic effects of mevinolin in patients with heterozygous familial hypercholesterolemia.
        J. Clin. Invest. 1984; 74: 1972-1978
        • Illingworth D.R.
        Comparative efficacy of once versus twice daily mevinolin in the therapy of familial hypercholesterolemia.
        Clin. Pharmacol. Ther. 1986; 40: 338-343
        • Havel R.J.
        • Hunninghake D.B.
        • Illlingworth D.R.
        • Lees R.S.
        • Stein E.A.
        • Tobert J.A.
        • Bacon S.R.
        • Bolognese J.A.
        • Frost P.H.
        • et al.
        Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia: a multicenter study.
        Ann. Intern. Med. 1987; 107: 609-615
        • Illlingworth D.R.
        Mevinolin plus colestipol in therapy for severe heterozygous familial hypercholesterolemia.
        Ann. Intern. Med. 1984; 101: 598-604
        • Grundy S.M.
        • Vega G.L.
        • Bilheimer D.W.
        Influence of combined therapy with mevinolin and interruption of bile-acid reabsorption on low density lipoproteins in heterozygous familial hypercholesterolemia.
        Ann. Intern. Med. 1985; 103: 339-343
        • The Lovastatin Study Group II
        Therapeutic response to lovastatin (mevinolin) in nonfamilial hypercholesterolemia: a multicenter study.
        JAMA. 1986; 256: 2829-2834
        • Hoeg J.M.
        • Maher M.B.
        • Zech L.A.
        • Bailey K.R.
        • Gregg R.E.
        • et al.
        Effectiveness of mevinolin on plasma lipoprotein concentrations in type II hyperlipoproteinemia.
        Am. J. Cardiol. 1986; 57: 933-939
        • East C.A.
        • Grundy S.M.
        • Bilheimer D.W.
        Preliminary report. Treatment of type 3 hyperlipoproteinemia with mevinolin.
        Metabolism. 1986; 35: 97-98
        • Vega G.L.
        • East C.A.
        • Grundy S.M.
        Lovastatin therapy in familial dysbetalipoproteinemia: effects on kinetics of apolipoprotein B..
        Atherosclerosis. 1988; 70: 131-143
        • Garg A.
        • Grundy S.M.
        Lovastatin for lowering cholesterol levels in noninsulin-dependent diabetes melli-tus.
        N. Engl. J. Med. 1988; 313: 81-86
        • Vega G.L.
        • Grundy S.M.
        Lovastatin therapy in nephrotic hyperlipidemia: effects on lipoprotein metabolism.
        Kidney Int. 1988; 33: 1160-1168
        • East C.
        • Bilheimer D.W.
        • Grundy S.M.
        Combination therapy for familial combined hyperlipidemia.
        Ann. Intern. Med. 1988; 109: 25-32
        • Yuan J.
        • Tsai M.Y.
        • Hegland J.
        • Hunninghake D.B.
        Effects of fluvastatin (XU-62320), an HMG-CoA reductase inhibitor, on the distribution and composition of low density lipoprotein subspecies in humans.
        Atherosclerosis. 1991; 87: 147-157
        • Angerbauer R.
        • Fey P.
        • Hübsch W.
        • Philipps T.
        • Schmidt D.
        Bay W 6228: a new generation HMG-CoA reductase inhibitor. I. Synthesis and structure activity relationships. XI International Symposium on Drugs Affecting Lipid Metabolism, Florence, Italy, 1992 (Abstract)
        • Beck G.
        • Kesseler K.
        • Baader E.
        • Bartman W.
        • Bergman A.
        • Granzer E.
        • Jendralla H.
        • von Kerekjarto B.
        • Krause R.
        • et al.
        Synthesis and biological activity of new HMG-CoA reductase inhibitors. 1. Lactones of pyridine-and pyrimidine-substituted 3,5-dihydroxy-6-heptenoic (-hep-tanoic) acids.
        J. Med. Chem. 1990; 33: 52-60
        • Hoffman W.F.
        • Alberts A.W.
        • Anderson P.S.
        • Chen J.S.
        • Smith R.L.
        • Willard A.K.
        3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors. 4. Side chain ester derivatives of mevinolin.
        J. Med. Chem. 1986; 29: 849-852
        • Mol M.J.T.M.
        • Erkelens D.W.
        • Leuren J.A.G.
        • Stalenhoef A.F.H.
        Effects of synvinolin (MK-733) on plasma lipids in familial hypercholesterolemia.
        Lancet. 1986; 2: 936-939
        • Olsson A.G.
        • Möłgaard J.
        • von Schenk H.
        Synvinolin in hypercholesterolemia.
        Lancet. 1986; 2: 390-391
        • Alberts A.W.
        Lovastatin and simvastatin.
        Cah. Nutr. Diet. 1988; 23: 231-234
        • Pietro D.A.
        • Alexander S.
        • Mantell G.
        • Staggers J.E.
        • Cook T.J.
        Effects of simvastatin and probucol in hypercholesterolemia (Simvastatin Multicenter Study Group II).
        Am. J. Cardiol. 1989; 63: 682-686
        • Ziegler O.
        • Drouin P.
        Simvastatin study group. Safety, tolerability, and efficacy of simvastatin and fenofibrate — a multicenter study.
        Cardiology. 1990; 77: 50-57
        • Todd P.A.
        • Goa K.L.
        Simvastatin - a review of its pharmacological properties and therapeutic potential in hypercholesterolemia.
        Drugs. 1990; 40: 583-607
        • Owens D.
        • Stinson J.
        • Collins P.
        • Johnson A.
        • Tomkin G.H.
        Improvement in the regulation of cellular cholesterogenesis in diabetes: the effect of reduction in serum cholesterol by simvastatin.
        Diabet. Med. 1991; 8: 151-156
        • Tsujita Y.
        • Kuroda M.
        • Shimada Y.
        • Tanzawa K.
        • Arai M.
        • Kaneko I.
        • Tanaka M.
        • Masuda H.
        • Tarumi C.
        • Watanabe Y.
        • Fujii S.
        CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effect on various animal species.
        Biochìm. Bìophys. Acta. 1986; 877: 50-60
        • Mabuchi H.
        • Kamon N.
        • Fujita H.
        • Michishita I.
        • Takeda M.
        • Kajinami K.
        • Ito H.
        • Wakasugi T.
        • Takeda R.
        Effects of CS-514 on serum lipoprotein lipid and apoprotein level in patients with familial hypercholesterolemia.
        Metabolism. 1987; 36: 475-479
        • Nakaya N.
        • Homma Y.
        • Tamachi H.
        • Shigematsu H.
        • Hata Y.
        • Goto Y.
        The effect of CS-514 on serum lipids and apolipoproteins in hypercholesterolemic subjects.
        JAMA. 1987; 257: 3088-3093
        • Hunninghake D.B.
        • Knopp R.H.
        • Schonfeld G.
        • Goldberg A.C
        • Brown W.V.
        • Schaefer E.J.
        • Margolis S.
        • Dobs A.S.
        • Mellies M.J.
        • Insull W.
        • Stein E.A.
        Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. I. A dose-response study.
        Atherosclerosis. 1990; 85: 81-89
        • Hoogerbrugge N.
        • van Dormaal J.T.
        • Rustemeijer C.
        • Mills E.
        • Stalenhoff A.F.
        • Birkenfager J.C.
        The efficacy and safety of pravastatin, compared to and in combination with bile acid binding resins, in familial hypercholesterolemia.
        J. Intern. Med. 1990; 228: 261-266
        • Vega G.L.
        • Krauss R.M.
        • Grundy S.M.
        Pravastatin therapy in primary moderate hypercholesterolemia: changes in metabolism of apolipoprotein B-containing lipoproteins.
        J. Intern. Med. 1990; 227: 81-94
        • Nestel P.J.
        • Eisenberg S.
        Nutrition and therapeutics: editorial overview.
        Curr. Opin. Lipidol. 1992; 3: 1-4
        • Illingworth D.R.
        • Bacon S.
        Hypolipidemic effects of HMG-CoA reductase inhibitors in patients with hypercholesterolemia.
        Am. J. Cardiol. 1987; 60: 33G-42G