on May 6, 2002
Published online before print May 6, 2002, doi: 10.1161/01.CIR.0000018744.58460.62
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© American Heart Association, Inc.
Clinical Investigation and Reports |
Efficacy and Safety of Ezetimibe Coadministered With Atorvastatin or Simvastatin in Patients With Homozygous Familial Hypercholesterolemia
From Chul du Chuq, Ste-Foy, Québec, Canada (C.G.); Community Genomic Medicine Center, Université de Montréal, and Lipid Clinic, Chicoutimi Hospital, Québec, Canada (D.G.); and Hôpital de la Pitié Salpêtrière, Paris, France (E.B.).
Reprint requests to Dr Claude Gagné, Chul du Chuq, CRML S-102 2705, Boulevard Laurier, Ste-Foy, Québec G1V 4G2 Canada.
Background— Patients with homozygous familial hypercholesterolemia (HoFH) have a high incidence of cardiovascular morbidity and mortality from premature atherosclerosis, and the efficacy of pharmacological therapy has been limited. We evaluated the efficacy, safety, and tolerability of ezetimibe, a novel cholesterol absorption inhibitor, in a multicenter, double-blind, randomized trial of HoFH patients receiving atorvastatin or simvastatin.
Methods and Results— Fifty patients with a diagnosis of HoFH on the National Cholesterol Education Program Step 1 or stricter diet and taking open-label atorvastatin 40 mg/d or simvastatin 40 mg/d (statin-40) with (n=25) or without (n=25) concomitant LDL apheresis were randomized to 1 of 3 double-blind treatments: atorvastatin or simvastatin 80 mg/d (statin-80, n=17); ezetimibe 10 mg/d plus atorvastatin or simvastatin 40 mg/d (n=16); or ezetimibe 10 mg/d plus atorvastatin or simvastatin 80 mg/d (n=17) for 12 weeks. The primary end point was mean percentage change in LDL cholesterol (LDL-C) from statin-40 baseline to the end point for patients receiving statins alone (statin-80) versus patients receiving ezetimibe plus atorvastatin or simvastatin at either dose (ezetimibe plus statin-40/80). Ezetimibe plus statin-40/80 significantly reduced LDL-C levels compared with statin-80 (-20.7% versus -6.7%, P=0.007). In the high-dose statin cohorts, ezetimibe plus statin-80 reduced LDL-C by an additional 20.5% (P=0.0001) versus statin-80. Similar significant reductions in LDL-C concentrations were observed for patients with genotype-confirmed HoFH (n=35). Ezetimibe was safe and well tolerated.
Conclusions— Ezetimibe coadministered with atorvastatin or simvastatin in patients with HoFH produced clinically important LDL-C reductions compared with best current therapy. Ezetimibe provides a new, complementary pharmacological approach for this high-risk population.
Key Words: hypercholesterolemia • lipoproteins • cholesterol • lipids • statins
This article has been cited by other articles:
 |
|
 |
|
  M. Sharma, M. T. Ansari, A. M. Abou-Setta, K. Soares-Weiser, T. C. Ooi, M. Sears, F. Yazdi, A. Tsertsvadze, and D. Moher Systematic Review: Comparative Effectiveness and Harms of Combination Therapy and Monotherapy for Dyslipidemia Ann Intern Med, November 3, 2009; 151(9): 622 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sharma, M. T. Ansari, A. M. Abou-Setta, K. Soares-Weiser, T. C. Ooi, M. Sears, F. Yazdi, A. Tsertsvadze, and D. Moher Systematic Review: Comparative Effectiveness and Harms of Combinations of Lipid-Modifying Agents and High-Dose Statin Monotherapy Ann Intern Med, August 31, 2009; (2009) 0000605-200911030-00144v1. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. J. Al Badarin, I. J. Kullo, S. L. Kopecky, and R. J. Thomas Impact of Ezetimibe on Atherosclerosis: Is the Jury Still Out? Mayo Clin. Proc., April 1, 2009; 84(4): 353 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-Y. Liu, Y.-W. Liu, L.-J. Lin, J.-H. Chen, and J. K. Liao Evidence for Statin Pleiotropy in Humans: Differential Effects of Statins and Ezetimibe on Rho-Associated Coiled-Coil Containing Protein Kinase Activity, Endothelial Function, and Inflammation Circulation, January 6, 2009; 119(1): 131 - 138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. O. Kwiterovich Jr. Recognition and Management of Dyslipidemia in Children and Adolescents J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4200 - 4209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. McCrindle, E. M. Urbina, B. A. Dennison, M. S. Jacobson, J. Steinberger, A. P. Rocchini, L. L. Hayman, and S. R. Daniels Drug Therapy of High-Risk Lipid Abnormalities in Children and Adolescents: A Scientific Statement From the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, With the Council on Cardiovascular Nursing Circulation, April 10, 2007; 115(14): 1948 - 1967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-E. W. Kavey, V. Allada, S. R. Daniels, L. L. Hayman, B. W. McCrindle, J. W. Newburger, R. S. Parekh, and J. Steinberger Cardiovascular Risk Reduction in High-Risk Pediatric Patients: A Scientific Statement From the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: Endorsed by the American Academy of Pediatrics Circulation, December 12, 2006; 114(24): 2710 - 2738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Huff, R. L. Pollex, and R. A. Hegele NPC1L1: Evolution From Pharmacological Target to Physiological Sterol Transporter Arterioscler Thromb Vasc Biol, November 1, 2006; 26(11): 2433 - 2438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Denke, T. Pearson, P. McBride, R. A Gazzara, W. E Brady, and A. M Tershakovec Ezetimibe added to ongoing statin therapy improves LDL-C goal attainment and lipid profile in patients with diabetes or metabolic syndrome Diabetes and Vascular Disease Research, September 1, 2006; 3(2): 93 - 102. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Oswald, S. Westrup, M. Grube, H. K. Kroemer, W. Weitschies, and W. Siegmund Disposition and Sterol-Lowering Effect of Ezetimibe in Multidrug Resistance-Associated Protein 2-Deficient Rats J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1293 - 1299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D Meyers, Y. S. Moon, H. Ghanem, and N. D Wong Type Of Preexisting Lipid Therapy Predicts LDL-C Response to Ezetimibe Ann. Pharmacother., May 1, 2006; 40(5): 818 - 823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Saito, A. Usui, T. Akita, and Y. Ueda Surgery for calcific aortic root stenosis in homozygous familial hypercholesterolemia Eur. J. Cardiothorac. Surg., January 1, 2006; 29(1): 114 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Mallare, A. H. Karabell, P. Velasquez-Mieyer, S. R.S. Stender, and M. L. Christensen Current and Future Treatment of Metabolic Syndrome and Type 2 Diabetes in Children and Adolescents Diabetes Spectr, October 1, 2005; 18(4): 220 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Clauss, K. W. Holmes, P. Hopkins, E. Stein, M. Cho, A. Tate, A. O. Johnson-Levonas, and P. O. Kwiterovich Efficacy and Safety of Lovastatin Therapy in Adolescent Girls With Heterozygous Familial Hypercholesterolemia Pediatrics, September 1, 2005; 116(3): 682 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.T. Ong The statin studies: from targeting hypercholesterolaemia to targeting the high-risk patient QJM, August 1, 2005; 98(8): 599 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Repa, S. D. Turley, G. Quan, and J. M. Dietschy Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption J. Lipid Res., April 1, 2005; 46(4): 779 - 789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 {blacktriangledown}Ezetimibe - a new cholesterol-lowering drug DTB, September 1, 2004; 42(9): 65 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R Thompson Management of dyslipidaemia Heart, August 1, 2004; 90(8): 949 - 955. [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Gotto Jr Targeting High-Risk Young Patients for Statin Therapy JAMA, July 21, 2004; 292(3): 377 - 378. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rees Review: Ezetimibe -- clinical and pharmacological profile The British Journal of Diabetes & Vascular Disease, May 1, 2004; 4(3): 163 - 171. [Abstract] [PDF]
|
|
|
|
|
|
R. Fux, K. Morike, U.-F. Gundel, R. Hartmann, and C. H. Gleiter Ezetimibe and Statin-Associated Myopathy Ann Intern Med, April 20, 2004; 140(8): 671 - 672. [Full Text] [PDF]
|
|
|
|
|
|
A. C. Sposito, S. Gonbert, E. Bruckert, M. Atassi, I. Beucler, S. Amsellem, O. Khallouf, P. Benlian, and G. Turpin Magnitude of HDL Cholesterol Variation After High-Dose Atorvastatin Is Genetically Determined at the LDL Receptor Locus in Patients With Homozygous Familial Hypercholesterolemia Arterioscler Thromb Vasc Biol, November 1, 2003; 23(11): 2078 - 2082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Friday Aggressive Lipid Management for Cardiovascular Prevention: Evidence from Clinical Trials Experimental Biology and Medicine, July 1, 2003; 228(7): 769 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bruckert, P. Giral, and P. Tellier Perspectives in Cholesterol-Lowering Therapy: The Role of Ezetimibe, a New Selective Inhibitor of Intestinal Cholesterol Absorption Circulation, July 1, 2003; 107(25): 3124 - 3128. [Full Text] [PDF]
|
|
|
|
|
|
V. F Mauro and C. E Tuckerman Ezetimibe for Management of Hypercholesterolemia Ann. Pharmacother., June 1, 2003; 37(6): 839 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Sacks Low-density lipoprotein lowering therapy: an analysis of the options J. Am. Coll. Cardiol., December 18, 2002; 40(12): 2135 - 2138. [Full Text] [PDF]
|
|
|
|
 |
|
 C.M. Ballantyne Ezetimibe: efficacy and safety in clinical trials Eur. Heart J. Suppl., December 1, 2002; 4(suppl_J): J9 - J18. [Abstract] [PDF]
|
|
|
|
|
|
N. Stone Combination therapy: its rationale and the role of ezetimibe Eur. Heart J. Suppl., December 1, 2002; 4(suppl_J): J19 - J22. [Abstract] [PDF]
|
|
|
|
|
|
J. J. Repa, J. M. Dietschy, and S. D. Turley Inhibition of cholesterol absorption by SCH 58053 in the mouse is not mediated via changes in the expression of mRNA for ABCA1, ABCG5, or ABCG8 in the enterocyte J. Lipid Res., November 1, 2002; 43(11): 1864 - 1874. [Abstract] [Full Text] [PDF]
|
|