Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia

Study Questions:

What is the efficacy of rosuvastatin as compared with placebo in children with homozygous familial hypercholesterolemia (HoFH)?


A multicenter, randomized, double-blind, crossover study of rosuvastatin 20 mg was performed. The 12-week placebo-controlled period was followed by 12 weeks of open-label rosuvastatin. Patients discontinued all lipid-lowering treatment except ezetimibe and/or apheresis. Clinical and laboratory assessments were performed every 6 weeks. The relationship between low-density lipoprotein cholesterol (LDL-C) response and genetic mutations was assessed by adding children and adults from a prior HoFH rosuvastatin trial.


Fourteen patients were randomized, of which 13 completed the study. The mean age was 10.9 years. At intake, eight patients were on ezetimibe and seven were on apheresis. For patients in the placebo group, mean LDL-C was 481 (range 229-742) mg/dl as compared with 396 (range 130-700) mg/dl on rosuvastatin, for a mean difference of 85.4 mg/dl (22.3%), p = 0.005. There was no difference in response to rosuvastatin for patients on apheresis or ezetimibe. There were few nonserious adverse events in either the treatment or placebo group. Patients with two defective versus two negative LDL receptor mutations had mean LDL-C reductions of 23.5% (p = 0.0044) and 14% (p = 0.038), respectively.


The authors concluded that rosuvastatin is safe and effective in reducing LDL-C in children with HoFH. The LDL-C response was related to underlying genetic mutations.


This is the first study to rigorously study the impact of statin therapy on LDL-C levels in children with HoFH. This is a good example of a therapy that has been widely implemented without placebo-controlled studies to support its use. The authors are to be complimented for taking a step back and confirming the safety and efficacy of statins in this patient population. The study also demonstrates the challenge of studying a very rare disease, in that despite this being a multicenter, international trial, only 14 patients were able to be enrolled of which 13 completed the study. Although this trial was relatively short in time frame and not designed to assess the impact of the treatment on hard cardiac events, the study does demonstrate a role for statins in decreasing LDL in children with HoFH.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins

Keywords: Child, Cholesterol, LDL, Dyslipidemias, Heart Defects, Congenital, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipoproteinemia Type II, Pediatrics, Primary Prevention, Rare Diseases, Receptors, LDL, Blood Component Removal

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