Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized, double-blind, placebo-controlled trial with simvastatin.
BACKGROUND
A multicenter, randomized, double-blind, placebo-controlled study was conducted to evaluate LDL cholesterol-lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia (heFH).


RESULTS
A total of 173 heFH children (98 boys and 75 girls) were included in this study. After a 4-week diet/placebo run-in period, children with heFH were randomized to either simvastatin or placebo in a ratio of 3:2. Simvastatin was started at 10 mg/d and titrated at 8-week intervals to 20 and then 40 mg/d. During a 24-week extension period, the patients continued to receive simvastatin (40 mg) or placebo according to their assignment. After 48 weeks of simvastatin therapy, there were significant reductions of LDL cholesterol (-41%), total cholesterol (-31%), apolipoprotein B (-34%), VLDL cholesterol (-21%), and triglyceride (-9%) levels. HDL cholesterol and apolipoprotein A-I levels were increased by 3.3% and 10.4%, respectively (not significant). No safety issues became evident. Except for small decreases in dehydroepiandrosterone sulfate compared with placebo, there were no significant changes from baseline in adrenal, gonadal, and pituitary hormones in either treatment group.


CONCLUSIONS
Simvastatin significantly reduced LDL cholesterol, total cholesterol, triglyceride, VLDL cholesterol, and apolipoprotein B levels and was well tolerated in children with heFH. There was no evidence of any adverse effect of simvastatin on growth and pubertal development. Therefore, simvastatin at doses up to 40 mg is a well-tolerated and effective therapy for heFH children.
de Jongh
Saskia
S
Department of Vascular Medicine, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.dejongh@amc.uva.nl
Ose
Leiv
L
Szamosi
Tamás
T
Gagné
Claude
C
Lambert
M
M
Scott
Russell
R
Perron
P
P
Dobbelaere
Dries
D
Saborio
M
M
Tuohy
Mary B
MB
Stepanavage
Michael
M
Sapre
Aditi
A
Gumbiner
Barry
B
Mercuri
Michele
M
van Trotsenburg
A S Paul
AS
Bakker
Henk D
HD
Kastelein
John J P
JJ
D000293:Adolescent; D001827:Body Height / Q000187:drug effects; D015992:Body Mass Index; D002648:Child; D004311:Double-Blind Method; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D012741:Sexual Maturation / Q000187:drug effects; D019821:Simvastatin / Q000009:adverse effects* / Q000627:therapeutic use*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008074:Lipoproteins; D019821:Simvastatin