The pivotal role of cholesterol absorption inhibitors in the management of dyslipidemia

Lipids in Health and Disease

Ehab S Suleiman¹  Nabil E Choueiri¹  Moutasim H Al-Shaer¹ 

[1] Department of Internal Medicine, and Human Cardiovascular Physiology Laboratory University of Iowa College of Medicine Iowa City, Iowa 52242-1009, USA

关键词: homozygous familial hypercholesterolemia;    Pleiotropic Effects of Statins;    Sitosterolemia;    Atherosclerosis;    Hypercholesterolemia;    Hyperlipidemia;    Dyslipidemia;    Cholesterol Absorption Inhibitors;    Zetia;    Ezetimibe;   

Others  :  1213283
DOI  :  10.1186/1476-511X-3-22

 received in 2004-09-23, accepted in 2004-10-07,  发布年份 2004

【 摘 要 】

Elevated low-density lipoprotein (LDL)-cholesterol is associated with a significantly increased risk of coronary heart disease. Ezetimibe is the first member of a new class of selective cholesterol absorption inhibitors. It impairs the intestinal reabsorption of both dietary and hepatically excreted biliary cholesterol. Ezetimibe is an effective and safe agent for lowering LDL-C and non HDL-C. Short term clinical trials have established the role of ezetimibe monotherapy and its use in combination with statins. Furthermore, ezetimibe and statin combination therapy increased the percentage of patients who achieved their LDL-C treatment goal.

Studies using surrogate markers of atherosclerosis have suggested a possible role of ezetimibe in combating atherosclerosis. Ezetimibe provides an effective therapeutic strategy for the management of homozygous familial hypercholesterolemia (HoFH) and sitosterolemia. The lack of outcomes and long term safety data is attributed to the relatively recent introduction of this medication.

【 授权许可】

   
2004 Al-Shaer et al; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Ford ES, Giles WH, Dietz WH: Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002, 287:356-9.
• [2]American Heart Association: Heart Disease and Stroke Statistics – 2004 Update. Dallas, Tex.: American Heart Association; © 2003 American Heart Association 2003.
• [3]National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106(25):3143-3421. 2002 Dec 17
• [4]Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM Jr: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998, 279(20):1615-1622.
• [5]Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ, for the West of Scotland Coronary Prevention Study Group: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995, 333:1301-1307.
• [6]Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E, for the Cholesterol and Recurrent Events Trial Investigators: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996, 335:1001-1009.
• [7]Scandinavian Simvastatin Survival Study Group: Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994, 344:1383-1389.
• [8]The Long-Term Intervention With Pravastatin in Ischaemic Disease (LIPID) Study Group: Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998, 339:1349-1357.
• [9]Ballantyne CM: Low-density lipoproteins and risk for coronary artery disease. Am J Cardiol 1998, 82(9A):3Q-12Q.
• [10]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; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Arterioscler Thromb Vasc Biol 2004, 24:e149-161.
• [11]Salisbury BG, Davis HR, Burrier RE, Burnett DA, Bowkow G, Caplen MA, Clemmons AL, Compton DS, Hoos LM, McGregor DG: Hypocholesterolemic activity of a novel inhibitor of cholesterol absorption, SCH 48461. Atherosclerosis 1995, 115:45-63.
• [12]Jeu L, Cheng JW: Pharmacology and therapeutics of ezetimibe (SCH 58235), a cholesterol-absorption inhibitor. Clin Ther 2003, 25:2352-87.
• [13]Nutescu EA, Shapiro NL: Ezetimibe: a selective cholesterol absorption inhibitor. Pharmacotherapy 2003, 23:1463-1474.
• [14]Van Heek M, France CF, Compton DS, McLeod RL, Yumibe NP, Alton KB, Sybertz EJ, Davis HR Jr: In vivo metabolism-based discovery of a potent cholesterol absorption inhibitor, SCH5 in the rat and rhesus monkey through the identification of the active metabolites of SCH48461. J Pharmacol Exp Ther 1997, 283:157-163.
• [15]Courtney RD, Kosoglou T, Statkevich P: Effect of food on the oral bioavailability of ezetimibe. Clin Pharmacol Ther 2002, 71:80. Abstract
• [16]Zetia [package insert] North Wales, Pa: Merck/Schering Plough Pharmaceuticals 2003.
• [17]Manel Barbanoj MD, PhD, Rosa Antonijoan MD, PhD, Adelaida Morte MD, Josep Ma Grinyó MD, PhD, Ricard Solà MD, PhD, Joaquim Vallès MD, PhD, Concepció Peraire PharmD, PhD, José CorderoA PharmD, PhD, Ana Muñoz BSc, Francesc Jané MD, PhD, Rossend Obach PharmD, PhD: Pharmacokinetics of Ezetimibe in subjects with normal renal function or severe chronic renal insufficiency. Clin Pharmacol Ther 2002, 71:27. Abstract
• [18]Harumi Takahashi PhDa, Shiro Ishikawa MD, PhDb, Shinichi Nomoto MD, PhDc, Yoshiyuki Nishigaki MDd, Fumitaka Ando MDd, Toshitaka Kashima MD, PhDe, Sosuke Kimura MD, PhDe, Madoka Kanamori MSa, Hirotoshi Echizen MD, PhD: Ezetimibe does not affect the pharmacokinetics or pharmacodynamics of warfarin. Clin Pharmacol Ther 2001, 69:5. Abstract
• [19]Reyderman L, Kosoglou T, Statkevich P: No pharmacokinetic drug interaction between ezetimibe and lovastatin. Clin Pharmacol Ther 2001, 69:66. Abstract
• [20]Zhu Y, Statkevich F', Kosoglou T: Lack of pharmacokinetic interaction between ezetimibe and atorvastatin. Clin Pharmacol Ther 2001, 69:68. Abstract
• [21]Fux R, Morike K, Gundel UF, Hartmann R, Gleiter CH: Ezetimibe and statin-associated myopathy. Ann Intern Med 2004, 140:671-2.
• [22]Bays HE, Moore PB, Drehobl MA, Rosenblatt S, Toth PD, Dujovne CA, Knopp RH, Lipka LJ, Lebeaut AP, Yang B, Mellars LE, Cuffie-Jackson C, Veltri EP, Ezetimibe Study Group: Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clin Ther 2001, 23:1209-1230.
• [23]Knopp RH, Dujovne CA, Le Beaut A, Lipka LJ, Suresh R, Veltri EP, Ezetimbe Study Group: Evaluation of the efficacy, safety, and tolerability of ezetimibe in primary hypercholesterolaemia: a pooled analysis from two controlled phase III clinical studies. Int J Clin Pract 2003, 57:363-368.
• [24]Dujovne CA, Ettinger MP, McNeer JF, Lipka LJ, LeBeaut AP, Suresh R, Yang B, Veltri EP, Esetimibe Study Group: Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol 90:1092-1097. 2002 Nov 15
• [25]Kerzner B, Corbelli J, Sharp S, Lipka LJ, Melani L, LeBeaut A, Suresh R, Mukhopadhyay P, Veltri EP, Ezetimibe Study Group: Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia. Am J Cardiol 91:418-424. 2003 Feb 15
• [26]Al-Shaer MH: The Effects of Ezetimibe on the LDL-Cholesterol Particle Number. Cardiovasc Drugs Ther 2004, 18:327-328.
• [27]Foley KA, Simpson RJ Jr, Crouse JR III, Weiss TW, Markson LE, Alexander CM: Effectiveness of statin titration on low-density lipoprotein cholesterol goal attainment in patients at high risk of atherogenic events. Am J Cardiol 2003, 92:79-81.
• [28]The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Group: Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA 2002, 288:2998-3007.
• [29]Roberts WC: The rule of 5 and the rule of 7 in lipid-lowering by statin drugs. Am J Cardiol 80:106-107. 1997 Jul 1
• [30]Gagne C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, Cho M, Musliner TA, Gumbiner B, Ezetimibe Study Group: Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol 90:1084-91. 2002 Nov 15
• [31]Gagne C, Gaudet D, Bruckert E, Ezetimibe Study Group: Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation 105:2469-2475. 2002 May 28
• [32]Bruckert E, Giral P, Tellier P: Perspectives in cholesterol-lowering therapy: the role of ezetimibe, a new selective inhibitor of intestinal cholesterol absorption. Circulation 107:3124-8. 2003 Jul 1
• [33]Davidson MH, McGarry T, Bettis R, Melani L, Lipka LJ, LeBeaut AP, Suresh R, Sun S, Veltri EP: Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol 2002, 40:2125-2134i.
• [34]Kosoglou T, Statkevich P, Fruchart JC, Pember LJ, Reyderman L, Cutler DL, Guillaume M, Maxwell SE, Veltri EP: Pharmacodynamic and pharmacokinetic interaction between fenofibrate and ezetimibe. Curr Med Res Opin 2004, 20(8):1197-1207.
• [35]Lu K, Lee MH, Hazard S, Brooks-Wilson A, Hidaka H, Kojima H, Ose L, Stalenhoef AF, Mietinnen T, Bjorkhem I, Bruckert E, Pandya A, Brewer HB Jr, Salen G, Dean M, Srivastava A, Patel SB: Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by abcg5 and abcg8, respectively. Am J Hum Genet 2001, 69:278-290.
• [36]Bhattacharyya AK, Connor WE: Beta-sitosterolemia and xanthomatosis: a newly described lipid storage disease in two sisters. J Clin Invest 1974, 53:1033-1043.
• [37]Nguyen LB, Shefer S, Salen G, Ness GC, Tint GS, Zaki FG, Rani I: A molecular defect in hepatic cholesterol biosynthesis in sitosterolemia with xanthomatosis. J Clin Invest 1990, 86:923-931.
• [38]Wang C, Lin HJ, Chan TK, Salen G, Chan WC, Tse TF: A unique patient with coexisting cerebrotendinous xanthomatosis and beta-sitosterolemia. Am J Med 1981, 71:313-319.
• [39]Miettinen TA: Phytosterolemia, xanthomatosis and premature atherosclerotic arterial disease: a case with high plant sterol absorption, impaired sterol elimination and low cholesterol synthesis. Europ J Clin Invest 1980, 10:27-35.
• [40]Kwiterovich PO Jr, Bachorik PS, Smith HH, McKusick VA, Connor WE, Teng B, Sniderman AD: Hyperapobetalipoproteinaemia in two families with xanthomas and phytosterolaemia. Lancet 1981, I:466-469.
• [41]Salen G, Horak I, Rothkopf M, Cohen JL, Speck J, Tint GS, Shore V, Dayal B, Chen T, Shefer S: Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis. J Lipid Res 1985, 26:1126-1133.
• [42]Salen G, von Bergmann K, Lutjohann D, Kwiterovich P, Kane J, Patel SB, Musliner T, Stein P, Musser B, Multicenter Sitosterolemia Study Group: Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation 109:966-971. 2004 Mar 2
• [43]Huff MW: Dietary cholesterol, cholesterol absorption, postprandial lipemia and atherosclerosis. Can J Clin Pharmacol 2003, Winter; 10(Suppl A):26A-32A.
• [44]Evans M, Roberts A, Rees A: The future direction of cholesterol-lowering therapy. Curr Opin Lipidol 2002, 13:663-669.
• [45]Sager PT, Melani L, Lipka L, Strony J, Yang B, Suresh R, Veltri E, Ezetimibe Study Group: Ezetimibe Study Group. Effect of coadministration of ezetimibe and simvastatin on high-sensitivity C-reactive protein. American Journal of Cardiology 2003, 92:1414-1418.
• [46]Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, Sun S, LeBeaut AP, Sager PT, Veltri EP, Ezetimibe Study Group: Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation 2003, 107:2409-2415.