Advertisement

Bile Acid Sequestrants: Do They Have a Future?

  • S. M. Grundy
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)

Abstract

It has been known for many years that interruption of the enterohepatic circulation (EHC) of bile acids will lower the plasma cholesterol. Interruption of the EHC can be achieved in several ways, but the usual means is by use of resins (sequestrants) that bind bile acids in the intestine and prevent their reabsorption. The bile acid sequestrants most commonly used are cholestyramine and colestipol. Cholestyramine was the drug used in the Lipid Research Clinics (LRC) Coronary Primary Prevention Trial (CPPT) (1,2). This trial tested cholestyramine vs placebo in about 4000 men with hypercholesterolemia who were treated for 7 years. Cholestyramine produced a significant lowering of the plasma cholesterol, and rates of coronary heart disease (CHD) were reduced significantly at p<0.05. This trial has generally been accepted as strong support for the “lipid hypothesis”, namely, that a lowering of the plasma cholesterol will decrease the risk for CHD. Furthermore, analysis of the trial results provided no consistent evidence that lowering of plasma cholesterol by bile acid sequestrants is accompanied by significant side effects. On the other hand, despite the success of the CPPT, doubts remain whether bile acid sequestrants have a significant future for the treatment of hypercholesterolemia. They are bulky and inconvenient to take. They can cause gastrointestinal distress, and they almost uniformly cause constipation. Also, they are only moderately effective for lowering of plasma cholesterol; and finally they are expensive.

Keywords

Bile Acid Reductase Inhibitor Plasma Cholesterol Bile Acid Sequestrant Lipid Research Clinic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lipid Research Clinics Program (1984) The lipid research clinics coronary primary prevention trial results. I. Reduction in incidence of coronary heart disease. JAMA 251:351–364CrossRefGoogle Scholar
  2. 2.
    Lipid Research Clinics Program (1984) The lipid research clinic primary prevention trial results. II. The relationship of reduction in incidence for coronary heart disease to cholesterol lowering. JAMA 251:365–374CrossRefGoogle Scholar
  3. 3.
    Kovanen PT, Bilheimer DW, Goldstein JL, Haramillo JJ, Brown MS (1981) Regulatory role for hepatic low density lipoprotein receptors in vivo in the dog. Proc Natl Acad Sci USA 78:1194–1198PubMedCrossRefGoogle Scholar
  4. 4.
    Packard CJ, Shepherd J (1982) The hepatobiliary axis and lipoprotein metabolism: effects of bile acid sequestrants and ileal bypass surgery. J Lipid Res 23:1081–1098PubMedGoogle Scholar
  5. 5.
    Goldstein JL, Brown MS (1977) The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem 46:897–930PubMedCrossRefGoogle Scholar
  6. 6.
    Grundy SM, Ahrens EH, Jr, Salen G (1971) Interruption of the enterohepatic circulation of bile acids in man: comparative effects of cholestyramine and ileal exclusion on cholesterol metabolism. J Lab Clin Med 78:94–121PubMedGoogle Scholar
  7. 7.
    McNamara PJ, Davidson NO, Fernandez S (1980) In vitro cholesterol synthesis in freshly isolated mononuclear cells of human blood: effect of Clofibrate and/or cholestyramine. J Lipid Res 21:65–71PubMedGoogle Scholar
  8. 8.
    Witztum JL, Schonfeld G, Wiedman SW, Giese WE, Dillingham MA (1979) Bile sequestrant therapy alters the composition of low density and high denstiy lipoproteins. Metabolism 28:221–229PubMedCrossRefGoogle Scholar
  9. 9.
    Witztum JL, Young SG, Elam RL, Carew TE, Fisher M (1985) Cholestyramine-induced changes in low density lipoprotein composition and metabolism. I. Studies in the guinea pig. J Lipid Res 26:92–103PubMedGoogle Scholar
  10. 10.
    Vega GL, Grundy SM (1986) Kinetic heterogeneity of low density lipoproteins in primary hypertriglyceridemia. Arteriosclerosis 6:395–406PubMedCrossRefGoogle Scholar
  11. 11.
    Grundy SM, Vega GL (1985) Influence of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia. J Lipid Res 26:1464–1475PubMedGoogle Scholar
  12. 12.
    Beil U, Grundy SM, Crouse JR, Zech L (1982) Triglyceride and cholesterol metabolism in primary hypertriglyceridemia. Arteriosclerosis 2:44–57PubMedCrossRefGoogle Scholar
  13. 13.
    Kesaniemi YA, Beltz WF, Grundy SM (1985) Comparisons of metabolism of apolipoprotein B in normal subjects, obese patients, and patients with coronary heart diesease. J Clin Invest 76:586–595PubMedCrossRefGoogle Scholar
  14. 14.
    Vega GL, Grundy SM (1985) Low density lipoprotein metabolism in hypertriglyceridemic and normolipidemic patients with coronary heart disease. J Lipid Res 26:115–126PubMedGoogle Scholar
  15. 15.
    Angelin B, Einarsson K (1981) Cholestyramine in type IIa hyperlipoproteinemia. Atheros-clerosis 38:33–38CrossRefGoogle Scholar
  16. 16.
    Yamamoto A, Sudo H, Endo A (1980) Therapeutic effects of ML-236B in primary hypercholesterolemia. Atherosclerosis 35:259–266PubMedCrossRefGoogle Scholar
  17. 17.
    Bilheimer DW, Grundy SM, Brown MS, Goldstein JL (1983) Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proc Natl Acad Sci 80:4124–4128PubMedCrossRefGoogle Scholar
  18. 18.
    Illingworth DR, Sexton GJ (1984) Hypocholesterolemia effects of mevinolin in patients with heterozygous familial hypercholesterolemia. J Clin Invest 74:1972–1978PubMedCrossRefGoogle Scholar
  19. 19.
    Grundy SM, Vega GL, Bilheimer DW (1985) Influence of combined therapy with mevinolin and interruption of bile acid reabsorption on low density lipoproteins in heterozygous familial hypercholesterolemia. Ann Int Med 103:339–343PubMedGoogle Scholar
  20. 20.
    Mabuchi H, Sakai T, Sakai Y, Yoshimura A, Watanabe T, Wakasugi T, Koizumi J, Takeda R (1983) Reduction of serum cholesterol in heterozygous patients with familial hypercholesterolemia. Additive effects of compactin and cholestyramine. N Engl J Med 308:609–613PubMedCrossRefGoogle Scholar
  21. 21.
    Vega GL, Grundy SM (1987) Treatment of primary moderate hypercholesterolemia with lovastatin (mevinolin) and colestipol. JAMA 257:33–38PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • S. M. Grundy
    • 1
  1. 1.Center for Human Nutrition, Department of Clinical NutritionUniversity of Texas Health Science Center at DallasDallasUSA

Personalised recommendations