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Short- and long-term effects of lovastatin and pravastatin alone and in combination with cholestyramine on serum lipids, lipoproteins and apolipoproteins in primary hypercholesterolaemia

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Summary

The effects of the HMG CoA reductase inhibitors lovastatin and pravastatin on serum lipids, lipoproteins and apolipoproteins have been studied in 35 patients with primary hypercholesterolaemia.

LDL cholesterol was lowered to the same extent by both agents compared on a mg basis of each drug per day. HDL cholesterol was increased by lovastatin but not by pravastatin. The reduction in serum triglycerides, VLDL triglycerides and VLDL cholesterol was more pronounced after lovastatin than pravastatin. After 1 year the effect of combined treatment with 40 mg pravastatin and 8 g cholestyramine on the reduction in LDL cholesterol (−39%) in 13 patients was comparable to that of 80 mg lovastatin plus 8 g cholestyramine (−40%) in 12 patients with identical baseline values.

Differences were also found in the effects of the combination therapy with the two drugs on HDL cholesterol, serum triglycerides, VLDL triglycerides, VLDL cholesterol, and apolipoproteins.

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References

  1. Kannel WB, Castelli WP, Gordon T (1979) Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study. Ann Intern Med 90: 85–91

    Google Scholar 

  2. Martin MJ, Hulley SB, Browner WS, Kuller LH, Wentworth D (1986) Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361,662 men. Lancet II: 933–936

    Google Scholar 

  3. Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, Huttunen JK, Kaitaniemi P, Koskinen P, Manninen V, et al. (1987) Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 317: 1237–1245

    Google Scholar 

  4. Lipid Research Clinics Program (1984) The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 251: 365–374

    Google Scholar 

  5. Havel RJ, Hunninghake DB, Illingworth DR, Lees RS, Stein EA, Tobert JA, Bacon SR, Bolognese JA, Frost PH, Lamkin GE, et al. (1987) Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia. A multicenter study. Ann Intern Med 107: 609–615

    Google Scholar 

  6. Ma PT, Gil G, Sudhof TC, Bilheimer DW, Goldstein JL, Brown MS (1986) Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits. Proc Natl Acad Sci USA 83: 8370–8374

    Google Scholar 

  7. Leren TP, Hjermann I, Berg K, Leren P, Foss OP, Viksmoen L (1988) Effects of lovastatin alone and in combination with cholestyramine on serum lipids and apolipoproteins in heterozygotes for familial hypercholesterolemia. Atherosclerosis 73: 135–141

    Google Scholar 

  8. Hoeg JM, Maher MB, Zech LA, Bailey KR, Gregg RE, Lackner KJ, Fojo SS, Anchors MA, Bojanovski M, Sprecher DL, et al. (1986) Effectiveness of mevinolin on plasma lipoprotein concentrations in type II hyperlipoproteinemia. Am J Cardiol 57: 933–939

    Google Scholar 

  9. The Lovastatin Study Group II (1986) Therapeutic response to lovastatin (mevinolin) in nonfamilial hypercholesterolemia. A multicenter study. JAMA 256: 2829–2834

    Google Scholar 

  10. The Lovastatin Study Group III (1988) A multicenter comparison of lovastatin and cholestyramine therapy for severe primary hypercholesterolemia. JAMA 260: 359–366

    Google Scholar 

  11. Mol MJTM, Erkelens DW, Leuven JA, Schouten JA, Stalenhoef AF (1986) Effects of synvinolin (MK-733) on plasma lipids in familial hypercholesterolaemia. Lancet II: 936–939

    Google Scholar 

  12. Leclercq V, Harvengt C (1989) Simvastatin (MK 733) in heterozygous familial hypercholesterolemia: a two-year trial. Int J Clin Pharmacol Ther Toxicol 27: 76–81

    Google Scholar 

  13. Nakaya N, Homma Y, Tamachi H, Shigematsu H, Hata Y, Goto Y (1987) The effect of CS-514 on serum lipids and apolipoproteins in hypercholesterolemic subjects. JAMA 257: 3088–3093

    Google Scholar 

  14. Saito Y, Goto Y, Nakaya N, Hata Y, Homma Y, Naito C, Hayashi H, Ito H, Yamamoto M, Takeuchi I, et al. (1988) Dose-dependent hypolipidemic effect of an inhibitor of HMG CoA reductase, pravastatin (CS-514), in hypercholesterolemic subjects. A double blind test. Atherosclerosis 72: 205–211

    Google Scholar 

  15. Saxenhofer H, Weidmann P, Riesen WF, Beretta-Piccoli C, Fragiacomo C, Wunderlin R, Noseda G (1990) Therapeutic efficacy of the HMG-CoA-reductase inhibitor pravastatin in hyperlipoproteinaemia type II. Eur J Clin Pharmacol 39: 101–105

    Google Scholar 

  16. Hunninghake DB, Knopp RH, Schonfeld G, Goldberg AC, Brown WV, Schaefer EJ, Margolis S, Dobs AS, Mellies MJ, Insull W Jr, et al. (1990) Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. I. A dose-response study. Atherosclerosis 85: 81–89

    Google Scholar 

  17. Owens D, Collins P, Johnson A, Tighe O, Robinson K, Tomkin GH (1991) Hypercholesterolaemia: simvastatin and pravastatin alter cholesterol metabolism by different mechanisms. Biochim Biophys Acta 1082: 303–309

    Google Scholar 

  18. Illingworth DR (1989) New horizons in combination drug therapy for hypercholesterolemia. Cardiology 76 [Suppl 1]: 83–94

    Google Scholar 

  19. Grundy SM (1988) HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med 319: 24–33

    Google Scholar 

  20. Hoffman WF, Alberts AW, Anderson PS, Chen JS, Smith RL, Willard AK (1986) 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 4. Side chain ester derivatives of mevinolin. J Med Chem 29: 849–852

    Google Scholar 

  21. Germershausen JI, Hunt VM, Bostedor RG, Bailey PJ, Karkas JD, Alberts AW (1989) Tissue selectivity of the cholesterol lowering agents lovastatin, simvastatin, and pravastatin in rats in vivo. Biochem Biophys Res Commun 158: 667–675

    Google Scholar 

  22. Sachs L (1974) Angewandte Statistik. Springer, Berlin Heidelberg New York

    Google Scholar 

  23. Illingworth DR (1987) Long term administration of lovastatin in the treatment of hypercholesterolaemia. Eur Heart J 8: 103–111

    Google Scholar 

  24. Tobert JA (1988) Efficacy and long-term adverse effect pattern of lovastatin. Am J Cardiol 62: 28J-34J

    Google Scholar 

  25. Bilheimer DW (1990) Long-term clinical tolerance of lovastatin and simvastatin. Cardiology 77 [Suppl 4]: 58–65

    Google Scholar 

  26. Yoshino G, Kazumi T, Iwai M, Matsushita M, Matsuba K, Uenoyama R, Iwatani I, Baba S (1989) Long-term treatment of hypercholesterolemic non-insulin dependent diabetics (NIDDM) with pravastatin (CS-514). Atherosclerosis 75: 67–72

    Google Scholar 

  27. Nozaki S, Vega GL, Haddox RJ, Dolan ET, Grundy SM (1990) Influence of lovastatin on concentrations and composition of lipoprotein subfractions. Atherosclerosis 84: 101–110

    Google Scholar 

  28. Grundy SM, Vega GL (1985) Influence of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia. J Lipid Res 26: 1464–1475

    Google Scholar 

  29. Mabuchi H, Kamon N, Fujita H, Michishita I, Takeda M, Kajinami K, Itoh H, Wakasugi T, Takeda R (1987) Effects of CS-514 on serum lipoprotein lipid and apolipoprotein levels in patients with familial hypercholesterolemia. Metabolism 36: 475–479

    Google Scholar 

  30. Hoogerbrugge N, Mol MJTM, Van Dormaal JJ, Rustemeijer C, Muls E, Stalenhoef AF, Birkenhager JC (1990) The efficacy and safety of pravastatin, compared to and in combination with bile acid binding resins, in familial hypercholesterolaemia. J Intern Med 228: 261–266

    Google Scholar 

  31. Kazumi T, Yoshino G, Kasama T, Iwatani I, Iwai M, Morita S, Baba S (1986) Effects of CS-514, a new inhibitor of HMG CoA reductase, on plasma lipids, lipoproteins and apoproteins in patients with primary hypercholesterolemia. Horm Metab Res 18: 654–655

    Google Scholar 

  32. Yoshino G, Kazumi T, Iwai M, Iwatani I, Matsuba K, Kasama T, Matsushita M, Otsuki M, Baba S (1988) Effects of CS-514 on plasma lipids and lipoprotein composition in hypercholesterolemic subjects. Atherosclerosis 71: 95–101

    Google Scholar 

  33. Brown MS, Kovanen PT, Goldstein JL (1981) Regulation of plasma cholesterol by lipoprotein receptors. Science 212: 628–635

    Google Scholar 

  34. Breslow JL (1985) Human apolipoprotein molecular biology and genetic variation. Ann Rev Biochem 54: 699–727

    Google Scholar 

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Jacob, B.G., Möhrle, W., Richter, W.O. et al. Short- and long-term effects of lovastatin and pravastatin alone and in combination with cholestyramine on serum lipids, lipoproteins and apolipoproteins in primary hypercholesterolaemia. Eur J Clin Pharmacol 42, 353–358 (1992). https://doi.org/10.1007/BF00280117

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  • DOI: https://doi.org/10.1007/BF00280117

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