Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia

Abstract

for the Simvastatin in Children Study GroupBackground-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). Methods and 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 (Ϫ41%), total cholesterol (Ϫ31%), apolipoprotein B (Ϫ34%), VLDL cholesterol (Ϫ21%), and triglyceride (Ϫ9%) 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.

A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes

“…In this context, statin therapy was shown to restore endothelial function in children with familial hypercholesterolemia 56 and has also demonstrated to be safe. 57 In conclusion, our cross-sectional data demonstrate that obese children have elevated blood levels of the inflammation markers hsCRP and hsIL-6 and of E-selectin, a specific endothelial activation marker. 58 These are markedly increased at a BMI Ն40 kg/m 2 .…”

Care of Children and Adolescents With Type 1 Diabetes

“…The introduction of bile acid sequestrants in tablet form may improve adherence. Short-term trials of HMG-CoA reductase inhibitors in youth have confirmed their safety and efficacy (168,169) in youth with familial hypercholesterolemia. These agents are approved for use in children Ն10 years of age with familial hypercholesterolemia.…”

Recommendations to Enhance Pediatric Cardiovascular Drug Development: Report of a Multi‐Stakeholder Think Tank

“…In each trial, the agent was specifically studied in familial hypercholesterolemia, using an established surrogate outcome (changes in lipid profiles). Impressively, all 8 studies led to efficacy‐related labeling changes 21, 22, 23, 24, 25, 26, 27, 28. The use of a specific patient population with markedly abnormal lipid profiles has been identified as a critical feature in the success of these trials.…”

“…Successful trials conducted under the regulatory incentive provisions have been primarily related to pediatric hypertension11, 12, 13, 14, 15, 16, 17, 18, 19, 20 and familial hypercholesterolemia 21, 22, 23, 24, 25, 26, 27, 28. Although these trials led to important changes for these particular diseases, they faced challenges related to patient recruitment, disease heterogeneity, dosing, endpoint selection, and, in general, an overall lack of experience in conducting randomized clinical trials in children.…”