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

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

Published online before print June 14, 2007
(Arteriosclerosis, Thrombosis, and Vascular Biology 2007, doi:10.1161/
ATVBAHA.107.145151)

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

From the Departments of Vascular Medicine (H.J.A., M.N.V., M.D.T.,
J.J.P.K.), Pediatrics (F.A.W.), 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.

* To whom correspondence should be addressed. E-mail:
b.a.hutten@xxxxxxxxxxx

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 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.

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