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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1803.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

A Systematic Review and Meta-Analysis of Statin Therapy in Children With Familial Hypercholesterolemia

H.J. Avis; M.N. Vissers; E.A. Stein; F.A. Wijburg; M.D. Trip; J.J.P. Kastelein; B.A. Hutten

From the Departments of Vascular Medicine (H.J.A., M.N.V., J.J.P.K.), Pediatrics (F.A.W.), Cardiology (M.D.T.), and Clinical Epidemiology, Biostatistics, and Bioinformatics (B.A.H.), Academic Medical Centre, Amsterdam, The Netherlands; and the Metabolic and Atherosclerosis Research Centre (E.A.S.), Cincinnati, Ohio.

Correspondence to Barbara A. Hutten, PhD, Academic Medical Centre, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail b.a.hutten{at}amc.uva.nl

Objective— Functional and morphological changes of the arterial wall already present in young children with heterozygous familial hypercholesterolemia (HeFH) suggest that treatment should be initiated early in life to prevent premature atherosclerotic cardiovascular disease. The purpose of this study was to assess the efficacy and particularly safety of statin therapy in children with HeFH.

Methods and Results— We performed a meta-analysis of randomized, double-blind, placebo-controlled trials evaluating statin therapy in children aged 8 to 18 years with HeFH. Six studies (n=798 children) with 12 to 104 weeks of treatment were included. Total cholesterol, LDL cholesterol, and apolipoprotein B were significantly reduced, whereas HDL cholesterol and apolipoprotein A1 were significantly increased by statin therapy. No statistically significant differences were found between statin- and placebo-treated children with respect to the occurrence of adverse events (RR 0.99; 95% CI: 0.79 to 1.25), sexual development (RR of advancing 1 stage in Tanner classification 0.96; 95% CI: 0.79 to 1.17), muscle toxicity (RR of CK 10 times the upper limit of normal [ULN] 1.38; 95% CI: 0.18 to 10.82), or liver toxicity (RR of 3 times the ULN for ASAT 0.98; 95% CI: 0.23 to 4.26 and for ALAT 2.03; 95% CI: 0.24 to 16.95). We found a minimal difference in growth in favor of the statin group (0.33 cm; 95% CI: 0.03 cm to 0.63 cm).

Conclusion— In addition to the fact that statin treatment is efficacious, our results support the notion that statin treatment in children with HeFH is safe. Thus, even though further studies are required to assess lifelong safety, statin treatment should be considered for all children aged 8 to 18 with HeFH.

This meta-analysis supports the notion that statin therapy is efficacious and safe in children with heterozygous familial hypercholesterolemia. Statin-treated children had a less atherogenic lipid profile and did not experience more adverse events, impaired growth and sexual development, or worsened laboratory safety profile when compared with placebo.

Key Words: familial hypercholesterolemia • children • statins • safety • meta-analysis

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