on September 30, 2002
Published online before print September 30, 2002, doi: 10.1161/01.CIR.0000035247.42888.82
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on June 14, 2002
From the Department of Vascular Medicine (S.d.J., H.D.B., J.J.P.K.) and Emma Children's Hospital (S.d.J., A.S.P.v.T., H.D.B.), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Lipidklinikken (L.O.), Med. Avd. Rikshospitalet, Oslo, Norway; the Second Department of Pediatrics (T.S.), Medical Faculty, Semmelweis University, Budapest, Hungary; Chul du Chuq (C.G.), Ste-Foy, Quebec, Canada; Service de Génétique Médicale (M.L.), Hôpital Ste-Justine, Québec, Canada; Christchurch Hospital (R.S.), Lipid and Diabetes Research Group, Canterbury, New Zealand; Clinique des Maladies Lipidiques (P.P.), Complexe Hospitalier de la Sagamie, Quebec, Canada; Hôpital Jeanne de Flandres (D.D.), Clinique Pediatric, Lille, France; Hospital Nacional de Niños (M. Saborio), San Jose, Costa Rica, and Merck Research Laboratories (M.B.T., M. Stepanavage, A.S., B.G., M.M.), Rahway, NJ. * To whom correspondence should be addressed. E-mail: s.dejongh{at}amc.uva.nl.
Background—A multicenter, randomized, double-blind, placebo-controlled study was conducted to evaluate LDL cholesterol-lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia (heFH). Methods and Results—A total of 173 heFH children (98 boys and 75 girls) were included in this study. After a 4-week diet/placebo run-in period, children with heFH were randomized to either simvastatin or placebo in a ratio of 3:2. Simvastatin was started at 10 mg/d and titrated at 8-week intervals to 20 and then 40 mg/d. During a 24-week extension period, the patients continued to receive simvastatin (40 mg) or placebo according to their assignment. After 48 weeks of simvastatin therapy, there were significant reductions of LDL cholesterol (-41%), total cholesterol (-31%), apolipoprotein B (-34%), VLDL cholesterol (-21%), and triglyceride (-9%) levels. HDL cholesterol and apolipoprotein A-I levels were increased by 3.3% and 10.4%, respectively (not significant). No safety issues became evident. Except for small decreases in dehydroepiandrosterone sulfate compared with placebo, there were no significant changes from baseline in adrenal, gonadal, and pituitary hormones in either treatment group. Conclusions—Simvastatin significantly reduced LDL cholesterol, total cholesterol, triglyceride, VLDL cholesterol, and apolipoprotein B levels and was well tolerated in children with heFH. There was no evidence of any adverse effect of simvastatin on growth and pubertal development. Therefore, simvastatin at doses up to 40 mg is a well-tolerated and effective therapy for heFH children.
Revised on August 9, 2002
Accepted on August 9, 2002
Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia. A Randomized, Double-Blind, Placebo-Controlled Trial With Simvastatin
Saskia de Jongh MD*,
Key words: cholesterol • drugs • hypercholesterolemia • lipids • pediatrics
This article has been cited by other articles:
 |
|
 |
|
  Y. Elgersma, L. C. Krab, and H. A. Moll Statin Therapy and Cognitive Deficits Associated With Neurofibromatosis Type 1--Reply JAMA, November 26, 2008; 300(20): 2369 - 2370. [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Pasquali and J. S. Li Prevention of Future Cardiovascular Disease in High-Risk Pediatric Patients: A Role for Lipid Lowering Therapy? Circ Cardiovasc Qual Outcomes, November 1, 2008; 1(2): 131 - 133. [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]
|
|
|
|
 |
|
 A. van der Graaf, C. Cuffie-Jackson, M. N. Vissers, M. D. Trip, C. Gagne, G. Shi, E. Veltri, H. J. Avis, and J. J.P. Kastelein Efficacy and Safety of Coadministration of Ezetimibe and Simvastatin in Adolescents With Heterozygous Familial Hypercholesterolemia J. Am. Coll. Cardiol., October 21, 2008; 52(17): 1421 - 1429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Kamerow Should we screen for and treat childhood dyslipidaemia? BMJ, July 23, 2008; 337(jul23_2): a886 - a886. [Full Text]
|
|
|
|
|
|
L. C. Krab, A. de Goede-Bolder, F. K. Aarsen, S. M. F. Pluijm, M. J. Bouman, J. N. van der Geest, M. Lequin, C. E. Catsman, W. F. M. Arts, S. A. Kushner, et al. Effect of Simvastatin on Cognitive Functioning in Children With Neurofibromatosis Type 1: A Randomized Controlled Trial JAMA, July 16, 2008; 300(3): 287 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Fernhall and S. Agiovlasitis Arterial function in youth: window into cardiovascular risk J Appl Physiol, July 1, 2008; 105(1): 325 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Daniels, F. R. Greer, and and the Committee on Nutrition Lipid Screening and Cardiovascular Health in Childhood Pediatrics, July 1, 2008; 122(1): 198 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. C. McGill Jr, C. A. McMahan, and S. S. Gidding Preventing Heart Disease in the 21st Century: Implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study Circulation, March 4, 2008; 117(9): 1216 - 1227. [Full Text] [PDF]
|
|
|
|
 |
|
 I. Romao, E. Klass, P. J. Westenend, R. Storm, R. J. Oostenbroek, and G. D. Braunstein Gynecomastia N. Engl. J. Med., December 20, 2007; 357(25): 2636 - 2637. [Full Text] [PDF]
|
|
|
|
|
|
E. A. Stein Statins and Children: Whom Do We Treat and When? Circulation, August 7, 2007; 116(6): 594 - 595. [Full Text] [PDF]
|
|
|
|
|
|
J. Rodenburg, M. N. Vissers, A. Wiegman, A. S. P. van Trotsenburg, A. van der Graaf, E. de Groot, F. A. Wijburg, J. J.P. Kastelein, and B. A. Hutten Statin Treatment in Children With Familial Hypercholesterolemia: The Younger, the Better Circulation, August 7, 2007; 116(6): 664 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.J. Avis, M.N. Vissers, E.A. Stein, F.A. Wijburg, M.D. Trip, J.J.P. Kastelein, and B.A. Hutten A Systematic Review and Meta-Analysis of Statin Therapy in Children With Familial Hypercholesterolemia Arterioscler Thromb Vasc Biol, August 1, 2007; 27(8): 1803 - 1810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Haney, L. H. Huffman, C. Bougatsos, M. Freeman, R. D. Steiner, and H. D. Nelson Screening and Treatment for Lipid Disorders in Children and Adolescents: Systematic Evidence Review for the US Preventive Services Task Force Pediatrics, July 1, 2007; 120(1): e189 - e214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. McCrindle and for the Writing Group Summary of the American Heart Association's Scientific Statement on Drug Therapy of High-Risk Lipid Abnormalities in Children and Adolescents Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 982 - 985. [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]
|
|
|
|
|
|
B. Belay, P. F. Belamarich, and C. Tom-Revzon The Use of Statins in Pediatrics: Knowledge Base, Limitations, and Future Directions Pediatrics, February 1, 2007; 119(2): 370 - 380. [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]
|
|
|
|
 |
|
 D S Celermajer and J. G J Ayer Childhood risk factors for adult cardiovascular disease and primary prevention in childhood. Heart, November 1, 2006; 92(11): 1701 - 1706. [Full Text] [PDF]
|
|
|
|
|
|
S. Kapiotis, G. Holzer, G. Schaller, M. Haumer, H. Widhalm, D. Weghuber, B. Jilma, G. Roggla, M. Wolzt, K. Widhalm, et al. A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes Arterioscler Thromb Vasc Biol, November 1, 2006; 26(11): 2541 - 2546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Reinehr, G. de Sousa, A. M. Toschke, and W. Andler Long-term follow-up of cardiovascular disease risk factors in children after an obesity intervention. Am. J. Clinical Nutrition, September 1, 2006; 84(3): 490 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Yuan, J. Wang, and R. A. Hegele Heterozygous familial hypercholesterolemia: an underrecognized cause of early cardiovascular disease. Can. Med. Assoc. J., April 11, 2006; 174(8): 1124 - 1129. [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]
|
|
|
|
|
|
M. Hedman, T. Matikainen, A. Fohr, M. Lappi, S. Piippo, M. Nuutinen, and M. Antikainen Efficacy and Safety of Pravastatin in Children and Adolescents with Heterozygous Familial Hypercholesterolemia: A Prospective Clinical Follow-Up Study J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 1942 - 1952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Silverstein, G. Klingensmith, K. Copeland, L. Plotnick, F. Kaufman, L. Laffel, L. Deeb, M. Grey, B. Anderson, L. A. Holzmeister, et al. Care of Children and Adolescents With Type 1 Diabetes: A statement of the American Diabetes Association Diabetes Care, January 1, 2005; 28(1): 186 - 212. [Full Text] [PDF]
|
|
|
|
 |
|
 W. A Prescott Jr, D.-a. D Streetman, and D. S Streetman The Potential Role of HMG-CoA Reductase Inhibitors in Pediatric Nephrotic Syndrome Ann. Pharmacother., December 1, 2004; 38(12): 2105 - 2114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R Thompson Management of dyslipidaemia Heart, August 1, 2004; 90(8): 949 - 955. [Full Text] [PDF]
|
|
|
|
|
|
A. Wiegman, B. A. Hutten, E. de Groot, J. Rodenburg, H. D. Bakker, H. R. Buller, E. J. G. Sijbrands, and J. J. P. Kastelein Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia: A Randomized Controlled Trial JAMA, July 21, 2004; 292(3): 331 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Greene and P. Durrington Clinical management of children and young adults with heterozygous familial hypercholesterolaemia in the UK J R Soc Med, May 1, 2004; 97(5): 226 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Reinehr and W Andler Changes in the atherogenic risk factor profile according to degree of weight loss Arch. Dis. Child., May 1, 2004; 89(5): 419 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Bloomgarden Type 2 Diabetes in the Young: The evolving epidemic Diabetes Care, April 1, 2004; 27(4): 998 - 1010. [Full Text] [PDF]
|
|
|
|
|
|
American Diabetes Association Management of Dyslipidemia in Children and Adolescents With Diabetes Diabetes Care, July 1, 2003; 26(7): 2194 - 2197. [Full Text] [PDF]
|
|