This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (108)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in JAMA  Topic Collections  • Nutritional and Metabolic Disorders  • Lipids and Lipid Disorders  • Randomized Controlled Trial  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Controlled Trial

Albert Wiegman, MD, PhD; Barbara A. Hutten, PhD; Eric de Groot, MD, PhD; Jessica Rodenburg, MD; Henk D. Bakker, MD, PhD; Harry R. Büller, MD, PhD; Eric J. G. Sijbrands, MD, PhD; John J. P. Kastelein, MD, PhD

JAMA. 2004;292:331-337.

Context  Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention therapy in the causal pathway of this disorder has been available for more than a decade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children.

Objective  To determine the 2-year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia.

Design  Randomized, double-blind, placebo-controlled trial that recruited children between December 7, 1997, and October 4, 1999, and followed them up for 2 years.

Setting and Participants  Two hundred fourteen children with familial hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical referral center in the Netherlands.

Intervention  After initiation of a fat-restricted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108).

Main Outcome Measures  The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 years; the principal safety outcomes were growth, maturation, and hormone level measurements over 2 years as well as changes in muscle and liver enzyme levels.

Results  Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean [SD], –0.010 [0.048] mm; P = .049), whereas a trend toward progression was observed in the placebo group (mean [SD], +0.005 [0.044] mm; P = .28). The mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was significant (P = .02). Also, pravastatin significantly reduced mean low-density lipoprotein cholesterol levels compared with placebo (–24.1% vs +0.3%, respectively; P<.001). No differences were observed for growth, muscle or liver enzymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups.

Conclusion  Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.

Author Affiliations: Departments of Vascular Medicine (Drs Wiegman, de Groot, Rodenburg, Büller, Sijbrands, and Kastelein), Paediatrics (Drs Wiegman and Bakker), and Clinical Epidemiology and Biostatistics (Dr Hutten), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, University of Rotterdam, Rotterdam, the Netherlands (Dr Sijbrands).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

Targeting High-Risk Young Patients for Statin Therapy

JAMA. ;292():377-378.
FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Noninvasive Assessment of Subclinical Atherosclerosis in Children and Adolescents: Recommendations for Standard Assessment for Clinical Research: A Scientific Statement From the American Heart Association
Urbina et al.
Hypertension 2009;54:919-950.
ABSTRACT | FULL TEXT  

Poor Performance of Body Mass Index as a Marker for Hypercholesterolemia in Children and Adolescents
Lee et al.
Arch Pediatr Adolesc Med 2009;163:716-723.
ABSTRACT | FULL TEXT  

Risk factors associated with aortic and carotid intima-media thickness in adolescents and young adults: the Muscatine Offspring Study.
Dawson et al.
J Am Coll Cardiol 2009;53:2273-2279.
ABSTRACT | FULL TEXT  

NICE guidance for identification and treatment of familial hypercholesterolaemia: Commentary 2
Durrington
Heart 2009;95:589-591.
FULL TEXT  

Standards of Medical Care in Diabetes--2009
American Diabetes Association
Diabetes Care 2009;32:S13-S61.
FULL TEXT  

Additional Lipid Lowering Trials Using Surrogate Measurements of Atherosclerosis by Carotid Intima-Media Thickness: More Clarity or Confusion?
Stein
J Am Coll Cardiol 2008;52:2206-2209.
FULL TEXT  

Efficacy of statins in familial hypercholesterolaemia: a long term cohort study
Versmissen et al.
BMJ 2008;337:a2423-a2423.
ABSTRACT | FULL TEXT  

Prevention of Future Cardiovascular Disease in High-Risk Pediatric Patients: A Role for Lipid Lowering Therapy?
Pasquali and Li
Circ Cardiovasc Qual Outcomes 2008;1:131-133.
FULL TEXT  

Recognition and Management of Dyslipidemia in Children and Adolescents
Kwiterovich
J. Clin. Endocrinol. Metab. 2008;93:4200-4209.
ABSTRACT | FULL TEXT  

Efficacy and Safety of Coadministration of Ezetimibe and Simvastatin in Adolescents With Heterozygous Familial Hypercholesterolemia
van der Graaf et al.
J Am Coll Cardiol 2008;52:1421-1429.
ABSTRACT | FULL TEXT  

Evidence Mandating Earlier and More Aggressive Treatment of Hypercholesterolemia
Steinberg et al.
Circulation 2008;118:672-677.
FULL TEXT  

Should we screen for and treat childhood dyslipidaemia?
Kamerow
BMJ 2008;337:a886-a886.
FULL TEXT  

Lipid Screening and Cardiovascular Health in Childhood
Daniels et al.
Pediatrics 2008;122:198-208.
ABSTRACT | FULL TEXT  

The ENHANCE Study and Marketing Ezetimibe
Akdim et al.
JAMA 2008;299:2747-2747.
FULL TEXT  

Preventing Heart Disease in the 21st Century: Implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study
McGill et al.
Circulation 2008;117:1216-1227.
FULL TEXT  

Utility of Currently Recommended Pediatric Dyslipidemia Classifications in Predicting Dyslipidemia in Adulthood: Evidence From the Childhood Determinants of Adult Health (CDAH) Study, Cardiovascular Risk in Young Finns Study, and Bogalusa Heart Study
Magnussen et al.
Circulation 2008;117:32-42.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes--2008
American Diabetes Association
Diabetes Care 2008;31:S12-S54.
FULL TEXT  

Statins and Children: Whom Do We Treat and When?
Stein
Circulation 2007;116:594-595.
FULL TEXT  

Statin Treatment in Children With Familial Hypercholesterolemia: The Younger, the Better
Rodenburg et al.
Circulation 2007;116:664-668.
ABSTRACT | FULL TEXT  

Review: Management of dyslipidemia in children and adolescents with systemic lupus erythematosus
Ardoin et al.
Lupus 2007;16:618-626.
ABSTRACT  

A Systematic Review and Meta-Analysis of Statin Therapy in Children With Familial Hypercholesterolemia
Avis et al.
Arterioscler. Thromb. Vasc. Bio. 2007;27:1803-1810.
ABSTRACT | FULL TEXT  

Screening and Treatment for Lipid Disorders in Children and Adolescents: Systematic Evidence Review for the US Preventive Services Task Force
Haney et al.
Pediatrics 2007;120:e189-e214.
ABSTRACT | FULL TEXT  

Atherosclerosis imaging in statin intervention trials
Yanai et al.
QJM 2007;100:253-262.
FULL TEXT  

Summary of the American Heart Association's Scientific Statement on Drug Therapy of High-Risk Lipid Abnormalities in Children and Adolescents
McCrindle and for the Writing Group
Arterioscler. Thromb. Vasc. Bio. 2007;27:982-985.
FULL TEXT  

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
McCrindle et al.
Circulation 2007;115:1948-1967.
ABSTRACT | FULL TEXT  

Carotid intima-media thickness and coronary atherosclerosis: weak or strong relations?
Bots et al.
Eur Heart J 2007;28:398-406.
ABSTRACT | FULL TEXT  

The Use of Statins in Pediatrics: Knowledge Base, Limitations, and Future Directions
Belay et al.
Pediatrics 2007;119:370-380.
ABSTRACT | FULL TEXT  

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
Kavey et al.
Circulation 2006;114:2710-2738.
ABSTRACT | FULL TEXT  

Prediction of Coronary Artery Calcium in Young Adults Using the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Risk Score: The CARDIA Study
Gidding et al.
Arch Intern Med 2006;166:2341-2347.
ABSTRACT | FULL TEXT  

Pathobiological Determinants of Atherosclerosis in Youth Risk Scores Are Associated With Early and Advanced Atherosclerosis
McMahan et al.
Pediatrics 2006;118:1447-1455.
ABSTRACT | FULL TEXT  

New Cholesterol Guidelines for Children?
Gidding
Circulation 2006;114:989-991.
FULL TEXT  

Diagnosing familial hypercholesterolaemia: the relevance of genetic testing
van Aalst-Cohen et al.
Eur Heart J 2006;27:2240-2246.
ABSTRACT | FULL TEXT  

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part V: The discovery of the statins and the end of the controversy
Steinberg
J. Lipid Res. 2006;47:1339-1351.
ABSTRACT | FULL TEXT  

Oxidized Low-Density Lipoprotein in Children With Familial Hypercholesterolemia and Unaffected Siblings: Effect of Pravastatin
Rodenburg et al.
J Am Coll Cardiol 2006;47:1803-1810.
ABSTRACT | FULL TEXT  

Heterozygous familial hypercholesterolemia: an underrecognized cause of early cardiovascular disease.
Yuan et al.
CMAJ 2006;174:1124-1129.
ABSTRACT | FULL TEXT  

Current and Future Treatment of Metabolic Syndrome and Type 2 Diabetes in Children and Adolescents
Mallare et al.
Diabetes Spectr. 2005;18:220-228.
ABSTRACT | FULL TEXT  

Efficacy and Safety of Lovastatin Therapy in Adolescent Girls With Heterozygous Familial Hypercholesterolemia
Clauss et al.
Pediatrics 2005;116:682-688.
ABSTRACT | FULL TEXT  

Risk Scores Predict Atherosclerotic Lesions in Young People
McMahan et al.
Arch Intern Med 2005;165:883-890.
ABSTRACT | FULL TEXT  

Efficacy and Safety of Pravastatin in Children and Adolescents with Heterozygous Familial Hypercholesterolemia: A Prospective Clinical Follow-Up Study
Hedman et al.
J. Clin. Endocrinol. Metab. 2005;90:1942-1952.
ABSTRACT | FULL TEXT  

Foreword
Cobbe and Kastelein
Eur Heart J Suppl 2005;7:A3-A4.
FULL TEXT  

Under-treated high-risk patients: identifying patients in high-risk subgroups and treating them to LDL-C targets
Schuster
Eur Heart J Suppl 2005;7:A20-A28.
ABSTRACT | FULL TEXT  

The Metabolic Syndrome: Look for It in Children and Adolescents, Too!
Jessup and Harrell
Clin. Diabetes 2005;23:26-32.
FULL TEXT  

Journal Watch
Arch. Dis. Child. 2005;90:106-107.
FULL TEXT  

JournalScan
Malik
Heart 2004;90:1235-1236.
FULL TEXT  

Statins for Kids with Familial Hypercholesterolemia?
Journal Watch Cardiology 2004;2004:2-2.
FULL TEXT  

Statin Therapy Is Effective and Safe for Children with Hypercholesterolemia
JWatch Pediatrics 2004;2004:1-1.
FULL TEXT  

Statin Therapy in Children
JWatch General 2004;2004:2-2.
FULL TEXT  

Targeting High-Risk Young Patients for Statin Therapy
Gotto
JAMA 2004;292:377-378.
FULL TEXT