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Wiegman A, Hutten BA, de Groot E, et al. Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia: A Randomized Controlled Trial. JAMA. 2004;292(3):331–337. doi:10.1001/jama.292.3.331
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).
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
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
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.
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