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European Heart Journal 2002 23(3):200-206; doi:10.1053/euhj.2001.3071
Copyright © 2002 by the European Society of Cardiology.
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Review

Why some patients respond poorly to statins and how this might be remedied

G.R. Thompsonf1, F. O'Neill and M. Seed

Departments of Investigative Science and Medicine, Imperial College School of Medicine, Hammersmith and Charing Cross Hospitals, London, U.K.

revised November 2, 2001; accepted November 7, 2001

Key Words: Cholesterol, cholestanol, campesterol, hyper-responder, hypo-responder, statin

f1 Correspondence: Emeritus Professor G. R. Thompson, Metabolic Medicine, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, U.K. e-mail:g.thompson@ic.ac.uk

References

  1. Ridker PM, Rifai N, Clearfield M. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;344:1959–1965[Abstract/Free Full Text]
  2. LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomised controlled trials. JAMA. 1999;282:2340–2346[Abstract/Free Full Text]
  3. JAMA. 1984;251:365–374[Abstract/Free Full Text]
  4. Simons LA, Simons J, McManus P, Dudley J. Discontinuation rates for use of statins are high. Br Med J. 2000;321:1084[Free Full Text]
  5. Cobb MM, Teitelbaum HS, Breslow JL. Lovastatin efficacy in reducing low-density lipoprotein cholesterol levels on high- vs low-fat diets. JAMA. 1991;265:997–1001[Abstract/Free Full Text]
  6. Chisholm A, Mann J, Sutherland W, Williams S, Ball M. Dietary management of patients with familial hypercholesterolaemia treated with simvastatin. Q J Med. 1992;85:825–831[Web of Science][Medline]
  7. Saito Y, Yoshida S, Nakaya N, Hata Y, Goto Y. Comparison between morning and evening doses of simvastatin in hyperlipidemic subjects. A double-blind comparative study. Arterioscler Thromb. 1991;11:816–826[Abstract/Free Full Text]
  8. Schachter M. Statins, drug interactions and cytochrome P450. Br J Cardiol. 2001;8:311–317
  9. Bottorff M, Hansten P. Long-term safety of hepatic Hydroxymethyl Glutaryl Coenzyme A reductase inhibitors. Arch Int Med. 2000;160:2273–2280[Free Full Text]
  10. Weber W. Drug firm withdraws statin from the market. Lancet. 2001;358:568[Medline]
  11. Naoumova RP, Marais AD, Mountney J. Plasma mevalonic acid, an index of cholesterol synthesis in vivo, and responsiveness to HMG CoA reductase inhibitors in familial hypercholesterolaemia. Atherosclerosis. 1996;119:203–213[CrossRef][Web of Science][Medline]
  12. Merck, information package DA- ZCR27(3)
  13. Pazzucconi F, Dorigotti F, Gianfranceschi G. Therapy with HMG CoA reductase inhibitors: characteristics of the long-term permanence of hypocholesterolemic activity. Atherosclerosis. 1995;117:189–198[CrossRef][Web of Science][Medline]
  14. Rubinstein A, Weintraub M. Escape phenomenon of low-density lipoprotein cholesterol during lovastatin treatment. Am J Cardiol. 1995;76:184–186[CrossRef][Web of Science][Medline]
  15. Thompson GR. Poor responders to statins: a potential target for stanol esters. Eur Heart J Suppl. 1991;1:S114–117
  16. Karayan L, Qiu S, Dufour R. Response to HMG CoA reductase inhibitors in heterozygous familial hypercholesterolaemia due to the 10-kb deletion (‘French Canadian Mutation’) of the LDL receptor gene. Arterioscler Thromb. 1994;14:1258–1263[Abstract/Free Full Text]
  17. Hernandez M, Montenegro J, Steiner M. Intestinal absorption of cholesterol is mediated by a saturable, inhibitable transporter. Biochim Biophys Acta. 2000;1486:232–242[Medline]
  18. Lee M-H, Lu K, Patel SB. Genetic basis of sitosterolemia. Curr Opin Lipidology. 2001;12:141–149[CrossRef][Web of Science][Medline]
  19. Berge KE, Tian H, Graft GA. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science. 2000;290:1775–1775[Abstract/Free Full Text]
  20. Dietschy JM, Turley SD, Spady DK. Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. J Lipid Res. 1993;34:1637–1659[Web of Science][Medline]
  21. Thompson GR. Genetic influence on cholesterol absorption and its therapeutic consequences. Leeds AR, Gray J. Dietary cholesterol as a cardiac risk factor: myth or reality?. London: Smith Gordon & Co Ltd; 2001. p. 27–33
  22. Sarkkinen E, Korhonen M, Erkkila A, Ebeling T, Uusitupa M. Effect of apolipoprotein E polymorphism on serum lipid response to the separate modification of dietary fat and dietary cholesterol. Am J Clin Nutr. 1998;68:1215–1222[Abstract]
  23. Kesaniemi YA, Enholm C, Miettinen TA. Intestinal cholesterol absorption efficiency in man is related to apoprotein E phenotype. J Clin Invest. 1987;80:578–581[Web of Science][Medline]
  24. Miettinen TA, Strandberg TE, Gylling H. Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients. Relation to basal serum cholesterol. Arterioscl Thromb Vasc Biol. 2000;20:1340–1346[Abstract/Free Full Text]
  25. Naoumova RP, Marais AD, Mountney J. Plasma mevalonic acid, an index of cholesterol synthesis in vivo, and responsiveness to HMG CoA reductase inhibitors in familial hypercholesterolaemia. Atherosclerosis. 1996;119:203–213[CrossRef][Web of Science][Medline]
  26. O'Neill FH, Patel DD, Knight BL. Determinants of variable response to statin treatment in patients with refractory familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2001;21:832–837[Abstract/Free Full Text]
  27. O'Malley JP, Illingworth DR. The influence of apolipoprotein E phenotype on the response to lovastatin therapy in patients with heterozygous familial hypercholesterolemia. Metabolism. 1990;39:150–154[CrossRef][Web of Science][Medline]
  28. De Knijff P, Stalenhoef AFH, Mol MJTM. Influence of apoE polymorphism on the response to simvastatin treatment in patients with heterozygous familial hypercholesterolemia. Atherosclerosis. 1990;83:89–97[CrossRef][Web of Science][Medline]
  29. Ojala JP, Helve E, Ehnholm C, Aalto-Setala K, Kontula KK, Tikkanen MJ. Effect of apolipoprotein E polymorphism and XbaI polymorphism of apolipoprotein B on response to lovastatin treatment in familial and non-familial hypercholesterolaemia. J Intern Med. 1991;230:397–405[Web of Science][Medline]
  30. Berglund L, Wiklund O, Eggertsen G. Apolipoprotein E phenotypes in familial hypercholesterolaemia: importance for expression of disease and response to therapy. J Int Med. 1993;233:173–178[Web of Science][Medline]
  31. Carmena R, Roederer G, Mailloux H, Lussier-Cacan S, Davignon J. The response to lovastatin treatment in patients with heterozygous familial hypercholesterolemia is modulated by apolipoprotein E polymorphism. Metabolism. 1993;42:895–901[CrossRef][Web of Science][Medline]
  32. Leitersdorf E, Eisenberg S, Eliav O. Genetic determinants of responsiveness to HMG-CoA reductase inhibitor fluvastatin in patients with molecularly defined heterozygous familial hypercholesterolemia. Circulation. 1993;87:III35–44
  33. Karayan L, Qiu S, Betard C. Response to HMG CoA reductase inhibitors in heterozygous familial hypercholesterolemia due to the 10-kb deletion (‘French Canadian mutation’) of the LDL receptor gene. Arterioscler Thromb. 1994;14:1258–1263[Abstract/Free Full Text]
  34. Ordovas JM, Lopez-Miranda J, Perez-Jimenez F. Effect of apolipoprotein E and A-IV phenotypes on the low density lipoprotein response to HMG CoA reductase inhibitor therapy. Atherosclerosis. 1995;113:157–166[CrossRef][Web of Science][Medline]
  35. Leren TP, Hjermann I. Is responsiveness to lovastatin in familial hypercholesterolaemia heterozygotes influenced by the specific mutation in the low-density lipoprotein receptor gene? Eur J Clin Invest. 1995;25:967–973[Web of Science][Medline]
  36. Ballantyne CM, Herd JA, Stein EA. Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy. J Am Coll Cardiol. 2000;36:1572–1578[Abstract/Free Full Text]
  37. Miettinen TA, Gylling H, Strandberg T, Sarna S. Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian Simvastatin Survival Study. Br Med J. 1998;316:1127–1130[Abstract/Free Full Text]
  38. Berger GMB, Pegoraro RJ, Patel SB. HMG-CoA reductase is not the site of the primary defect in phytosterolemia. J Lipid Res. 1998;39:1046–1054[Abstract/Free Full Text]
  39. O'Neill FH, Mandeno R, Thompson GR, Seed M. Enhancement of cholesterol-lowering effect of atorvastatin by stanol ester cereal bars. Atherosclerosis Suppl. 2001;2/2:110
  40. Bays H, Drehobl M, Rosenblatt S. Low-density lipoprotein cholesterol reduction by SCH58235 (ezetimibe), a novel inhibitor of intestinal cholesterol absorption in 243 hypercholesterolemic subjects: Results of a dose-response study. Atherosclerosis. 2000;151:135
  41. Thompson GR. Plant lipids that lower serum cholesterol. Eur Heart J. 1999;20:1527–1529[Free Full Text]
  42. Gylling H, Miettinen TA. Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic men. J Lipid Res. 1996;37:1776–1785[Abstract]
  43. Gylling H, Radhakrishnan R, Miettinen TA. Reduction of serum cholesterol in postmenopausal women with previous myocardial infarction and cholesterol malabsorption induced by dietary sitostanol ester margarine: women and dietary sitostanol. Circulation. 1997;96:4226–4231[Abstract/Free Full Text]
  44. Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolaemia caused by the FH–North Karelia mutation. Arterioscler Thromb Vasc Biol. 2000;20:500–506[Abstract/Free Full Text]
  45. Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB. Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy. Am J Cardiol. 2000;86:46–52[Web of Science][Medline]
  46. Kosoglou T, Meyer I, Musiol B. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin. Atherosclerosis. 2000;151:135
  47. Gylling H, Miettinen TA. Sitostanol ester added to long-term simvastatin treatment of coronary patients with low and high basal cholesterol absorption. Atherosclerosis. 1997;134:157
  48. Thompson GR, Naoumova RP. Novel lipid-regulating drugs. Exp Opin Invest Drugs. 2000;9:2619–2628[CrossRef]

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