Efficacy and Safety of Statin Therapy in Children... : JAMA: The Journal of the American Medical Association (original) (raw)

Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia

A Randomized Controlled Trial

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

JAMA: The Journal of the American Medical Association

292

(

)

331

337

July 21, 2004

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.