PEDIATRICS Vol. 97 No. 5 May 1996, pp. 619-628
This Article
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lambert, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lambert, M.

Treatment of Familial Hypercholesterolemia in Children and Adolescents: Effect of Lovastatin

Marie Lambert MD1, Paul-J Lupien MD, PhD2, Claude Gagné MD2, Emile Lévy PhD3, Shirley Blaichman MD4, Sylvie Langlois MD5, Michael Hayden MD, PhD6, Vera Rose MD7, Joe T. R. Clarke MD, PhD8, Bernard M. J. Wolfe BM, BCh9, Cheril Clarson MD10, Howard Parsons MD11, David K Stephure MD11, Diane Potvin MSc12, Jean Lambert PhD12, and Canadian Lovastatin in Children Study Group

1 Medical Genetics Service, Department of Nutrition, Hôpital Sainte-Justine and Université de Montréal, Québec
2 Lipid Research Center, Centre Hospitalier de l'Université Laval and Université Laval, Ste-Foy, Québec
3 Department of Nutrition, Hôpital Sainte-Justine and Université de Montréal, Québec
4 Department of Pediatrics, Montreal Children's Hospital and McGill University, Vancouver
5 Department of Medical Genetics, British Columbia Children's Hospital, Vancouver; Department of Medical Genetics, University of British Columbia, Vancouver
6 Department of Medical Genetics, University of British Columbia, Vancouver
7 Department of pediatrics, Hospital for Sick Children and University of Toronto, Ontario
8 Department of Pediatrics, Hospital for Sick Children and University of Toronto, Ontario
9 University Hospital, London, Ontario
10 Children's Hospital of Western Ontario, London, Ontario
11 Department of Pediatrics, Alberta Children's Hospital and University of Calgary
12 Department of Social and Preventive Medicine, Université de Montréal

Objective. Familial hypercholesterolemia (FH), an inherited autosomal dominant disorder of lipoprotein metabolism, is associated with premature atherosclerosis. The recommended pediatric therapy consists of dietary intervention and, when necessary, treatment with bile acid-binding resins. However, compliance has been poor in many children. Therefore, our objectives were to determine the efficacy, safety, and tolerance of the short-term use of lovastatin, a 3-hydroxy 3-methylglutaryl coenzyme A reductase inhibitor, in the control of severe FH in a male pediatric population and to evaluate the dose-response relationship.

Methods. Sixty-nine male patients with FH 12.9 ± 2.4 years of age (mean ± SD) participated in this multicenter, randomized, double-blind trial. After a 4-week placebo period, the patients were allocated to four treatment groups (lovastatin 10, 20, 30, or 40 mg/d) for 8 weeks. Plasma lipid and apolipoprotein (Apo) concentrations were measured every 2 weeks. Clinical and laboratory evidence of adverse events was monitored periodically throughout the study.

Results. All lovastatin doses reduced total cholesterol (—17% to —29%), low-density lipoprotein cholesterol (—21% to —36%), and ApoB (—19% to —28%) concentrations. A dose-response relationship was seen, and between-group comparisons showed that results were significantly improved up to a dose of 30 mg/d. We observed a 7% increase in high-density lipoprotein cholesterol and a 4% increase in ApoA1 concentrations. The medication was well tolerated by all patients. No serious clinical adverse experience was reported. Lovastatin increased aspartate aminotransferase concentrations, but there was no evidence of a dose-response relationship, and no value exceeded two times the upper limit of normal. No significant change in alanine aminotransferase was observed. Three patients had marked (more than three times the upper limit of normal) asymptomatic elevations in their creatine kinase values, which returned spontaneously to normal, and no action was required regarding the drug.

Conclusions. Lovastatin is an effective therapy for severe FH in children and adolescents. It was well tolerated, and the occurrence of adverse experiences of clinical significance was very low. Long-term pediatric studies are indicated.

Submitted on February 27, 1995
Accepted on August 10, 1995




This article has been cited by other articles:


Home page
 PediatricsHome page
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]

Home page
 PediatricsHome page
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]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
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]

Home page
 CirculationHome page
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]

Home page
 PediatricsHome page
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]

Home page
 CirculationHome page
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]

Home page
 PediatricsHome page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 The Annals of PharmacotherapyHome page
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]

Home page
 JAMAHome page
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]

Home page
 J Am Coll CardiolHome page
S. de Jongh, M. R. Lilien, J. op't Roodt, E. S. G. Stroes, H. D. Bakker, and J. J. P. Kastelein
Early statin therapy restores endothelial function in children with familial hypercholesterolemia
J. Am. Coll. Cardiol., December 18, 2002; 40(12): 2117 - 2121.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
S. de Jongh, L. Ose, T. Szamosi, C. Gagne, M. Lambert, R. Scott, P. Perron, D. Dobbelaere, M. Saborio, M. B. Tuohy, et al.
Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia: A Randomized, Double-Blind, Placebo-Controlled Trial With Simvastatin
Circulation, October 22, 2002; 106(17): 2231 - 2237.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
P. E. Jira, R. A. Wevers, J. de Jong, E. Rubio-Gozalbo, F. S. M. Janssen-Zijlstra, A. F. J. van Heyst, R. C. A. Sengers, and J. A. M. Smeitink
Simvastatin: a new therapeutic approach for Smith-Lemli-Opitz syndrome
J. Lipid Res., August 1, 2000; 41(8): 1339 - 1346.
[Abstract] [Full Text]

Home page
 JAMAHome page
E. A. Stein, D. R. Illingworth, P. O. Kwiterovich Jr, C. A. Liacouras, M. A. Siimes, M. S. Jacobson, T. G. Brewster, P. Hopkins, M. Davidson, K. Graham, et al.
Efficacy and Safety of Lovastatin in Adolescent Males With Heterozygous Familial Hypercholesterolemia: A Randomized Controlled Trial
JAMA, January 13, 1999; 281(2): 137 - 144.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
B. M. Rifkind, B. Schucker, and D. J. Gordon
When Should Patients With Heterozygous Familial Hypercholesterolemia Be Treated?
JAMA, January 13, 1999; 281(2): 180 - 181.
[Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
P. Couture, L. D. Brun, F. Szots, M. Lelievre, D. Gaudet, J.-P. Despres, J. Simard, P. J. Lupien, and C. Gagne
Association of Specific LDL Receptor Gene Mutations With Differential Plasma Lipoprotein Response to Simvastatin in Young French Canadians With Heterozygous Familial Hypercholesterolemia
Arterioscler. Thromb. Vasc. Biol., June 1, 1998; 18(6): 1007 - 1012.
[Abstract] [Full Text] [PDF]