Efficacy of ezetimibe as monotherapy or combination therapy in hypercholesterolemic patients with and without diabetes

Ezetimibe selectively inhibits dietary and biliary cholesterol absorption and reduces serum cholesterol levels when administered alone (monotherapy) and along with common lipid-regulating agents (combination therapy). To evaluate the effect of ezetimibe therapy on the lipid profile, glucose metaboli...

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Published inThe Journal of Medical Investigation Vol. 58; no. 1,2; pp. 86 - 94
Main Authors Osame, Keiichiro, Sugiyama, Takehiro, Noda, Mitsuhiko, Takarabe, Daisuke, Kishimoto, Miyako, Okamoto, Masahide
Format Journal Article
LanguageEnglish
Published The University of Tokushima Faculty of Medicine 2011
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ISSN1343-1420
1349-6867
1349-6867
DOI10.2152/jmi.58.86

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Abstract Ezetimibe selectively inhibits dietary and biliary cholesterol absorption and reduces serum cholesterol levels when administered alone (monotherapy) and along with common lipid-regulating agents (combination therapy). To evaluate the effect of ezetimibe therapy on the lipid profile, glucose metabolism, and levels of cholesterol absorption and synthesis markers, we administered 10 mg ezetimibe to 50 hypercholesterolemic patients with or without diabetes. The serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly reduced at 4 and 12 weeks of ezetimibe therapy in diabetic patients of both the monotherapy and combination-therapy groups and in nondiabetic patients of the combination-therapy group. The serum levels of the cholesterol absorption markers were significantly reduced, while those of the cholesterol synthesis markers were significantly increased at 12 weeks of ezetimibe therapy. No significant differences were noted in the values of the parameters of glucose metabolism in all patients. We also investigated the clinical characteristics of patients who exhibited a good response to ezetimibe (ezetimibe responders); however, multivariate regression analysis did not reveal a correlation between ezetimibe efficacy and patient characteristics such as gender, age, BMI, diabetic condition, method of ezetimibe administration, and the initial absolute values of cholesterol absorption/synthesis markers levels. In conclusion, ezetimibe therapy significantly improved the lipid profile without disturbing glucose metabolism. We were unable to identify the specific characteristics of ezetimibe responders among our subjects. However, we may interpret this result as suggesting that ezetimibe can be used in any population to lower low-density lipoprotein cholesterol levels. J. Med. Invest. 58: 86-94, February, 2011
AbstractList Ezetimibe selectively inhibits dietary and biliary cholesterol absorption and reduces serum cholesterol levels when administered alone (monotherapy) and along with common lipid-regulating agents (combination therapy). To evaluate the effect of ezetimibe therapy on the lipid profile, glucose metabolism, and levels of cholesterol absorption and synthesis markers, we administered 10 mg ezetimibe to 50 hypercholesterolemic patients with or without diabetes. The serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly reduced at 4 and 12 weeks of ezetimibe therapy in diabetic patients of both the monotherapy and combination-therapy groups and in nondiabetic patients of the combination-therapy group. The serum levels of the cholesterol absorption markers were significantly reduced, while those of the cholesterol synthesis markers were significantly increased at 12 weeks of ezetimibe therapy. No significant differences were noted in the values of the parameters of glucose metabolism in all patients. We also investigated the clinical characteristics of patients who exhibited a good response to ezetimibe (ezetimibe responders); however, multivariate regression analysis did not reveal a correlation between ezetimibe efficacy and patient characteristics such as gender, age, BMI, diabetic condition, method of ezetimibe administration, and the initial absolute values of cholesterol absorption/synthesis markers levels. In conclusion, ezetimibe therapy significantly improved the lipid profile without disturbing glucose metabolism. We were unable to identify the specific characteristics of ezetimibe responders among our subjects. However, we may interpret this result as suggesting that ezetimibe can be used in any population to lower low-density lipoprotein cholesterol levels. J. Med. Invest. 58: 86-94, February, 2011
Author Osame, Keiichiro
Sugiyama, Takehiro
Takarabe, Daisuke
Okamoto, Masahide
Kishimoto, Miyako
Noda, Mitsuhiko
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  fullname: Osame, Keiichiro
  organization: Department of Diabetes and Metabolic Medicine, National Center for Global Health and Medicine
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  fullname: Sugiyama, Takehiro
  organization: Department of Diabetes and Metabolic Medicine, National Center for Global Health and Medicine
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  fullname: Noda, Mitsuhiko
  organization: Department of Diabetes and Metabolic Medicine, National Center for Global Health and Medicine
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  fullname: Takarabe, Daisuke
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  fullname: Kishimoto, Miyako
  organization: Department of Diabetes and Metabolic Medicine, National Center for Global Health and Medicine
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  fullname: Okamoto, Masahide
  organization: Department of Diabetes and Metabolic Medicine, National Center for Global Health and Medicine
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References_xml – reference: 25. Pearson TA, Denke MA, McBride PE, Battisti WP, Brady WE, Palmisano J: A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: The Ezetimibe Add-On to Statin for Effecticeness (EASE) trial. Mayo Clin Proc 80: 587-595, 2005
– reference: 4. Miettinen TA, Gylling H, Strandberg T, Sarna D: Baseline serum cholesterol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. BMJ 316: 1127-1130, 1988
– reference: 13. Altmann SW, Davis HR Jr, Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP, Maguire M, Golovko A, Zeng M, Wang L, Murgolo N, Graziano MP: Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 303: 1201-1204, 2004
– reference: 45. Sager PT, Capece R, Lipka L, Strony J, Yang B, Suresh R, Mitchel Y, Veltri E: Effects of ezetimibe coadministered with simvastatin on C-reactive protein in a large cohort of hypercholesterolemic patients. Atherosclerosis 179: 361-367, 2005
– reference: 6. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM: Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 35: 1495-1504, 2004
– reference: 19. The Committee of Japan diabetes society on the diagnosis criteria of diabetes mellitus. Report of the Committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Invest 1: 212-228, 2010
– reference: 16. Derosa G, D’Angelo A, Franzetti IG, Ragonesi PD, Gadaleta G, Scalise F, Ciccarelli L, Piccinni MN, Cicero AF: Efficacy and safety of ezetimibe/simvastatin association on non-diabetic and diabetic patients with polygenic hypercholesterolemia or combined hyperlipidemia and previously intolerant to standard statin treatment. J Clin Pharm Ther 34: 267-276, 2009
– reference: 38. Chan DC, Watts GF, Barrett PH, O’Neill FH, Thompson GR: Plasma markers of cholesterol homeostasis and apolipoprotein B-100 kinetics in the metabolic syndrome. Obes Res 11: 591-596, 2003
– reference: 37. Miettinen TA, Gylling H, Viikari J, Lehtimäki T, Raitakari OT: Synthesis and absorption of cholesterol in Finnish boys by serum non-cholesterol sterols. The cardiovascular risk in young Finns study. Atherosclerosis 200: 177-183, 2008
– reference: 10. Harris M., Davis W., Brown WV: Ezetimibe. Drugs of Today 39: 229-247, 2003
– reference: 21. Ezetimibe for the treatment of hypercholesterolaemia: a systematic review and economic evaluation. Ara R, Tumur I, Pandor A, Duenas A, Williams R, Wilkinson A, Paisley S, Chilcott J: Ezetimibe for the treatment of hypercholesterolaemia: a systematic review and economic evaluation. Health Technol Assess 12: 1-212, 2008
– reference: 9. Armitage J: The safety of statins in clinical practice. Lancet 370: 1781-1790, 2007
– reference: 1. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ: Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. J Am Coll Cardiol 44: 720-732, 2004
– reference: 44. Pearson TA, Ballantyne CM, Veltri E, Shah A, Bird S, Lin J, Rosenberg E, Tershakovec AM: Pooled analyses of effects on C-reactive protein and low density lipoprotein cholesterol in placebo-controlled trials of ezetimibe monotherapy or ezetimibe added to baseline statin therapy. Am J Cardiol 103: 369-374, 2009
– reference: 12. Davies JP, Levy B, Ioannou YA: Evidence for a Niemann-pick C (NPC) gene family: identification and characterization of NPC1L1. Genomics 65: 137-145, 2000
– reference: 26. Hoenig MR, Rolfe BE, Campbell JH: Cholestanol: A serum marker to guide LDL cholesterol-lowering therapy. Atherosclerosis 184: 247-254, 2006
– reference: 7. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK; Treating to New Targets (TNT) Investigators: Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 352: 1425-1435, 2005
– reference: 14. Davis HR Jr, Hoos LM, Tetzloff G, Maguire M, Zhu LJ, Graziano MP, Altmann SW: Deficiency of Niemann-Pick C1 Like 1 prevents atherosclerosis in ApoE-/- mice. Arterioscler Thromb Vasc Biol 27: 841-849, 2007
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Snippet Ezetimibe selectively inhibits dietary and biliary cholesterol absorption and reduces serum cholesterol levels when administered alone (monotherapy) and along...
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SubjectTerms cholesterol absorption
cholesterol synthesis
ezetimibe
hypercholesterolemia
Title Efficacy of ezetimibe as monotherapy or combination therapy in hypercholesterolemic patients with and without diabetes
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