Familial hypercholesterolemia is one of the most common inherited metabolic diseases; the average worldwide prevalence of heterozygous familial hypercholesterolemia is about 1 in 500. Diagnosis of familial hypercholesterolemia in children is based on two measurements of low-density lipoprotein cholesterol level above 4.0 mmol/L or a DNA-based analysis. Coronary stenosis has been detected in men with familial hypercholesterolemia as young as 17 years old and in women with familial hypercholesterolemia at 25 years of age. Atherosclerosis and its clinical complications occur prematurely, especially in men, thus lifelong hypolipidemic measures, started in childhood, are needed to reduce the risk of cardiovascular diseases. In children with familial hypercholesterolemia, diet has been the main mode of treatment. Anion exchange resins, such as cholestyramine and colestipol, have also been found to be effective but are generally considered unpalatable and therefore poorly tolerated. Since the 1990s statin trials have been carried out among children with familial hypercholesterolemia (aged 7 to 17 years), and statins reduced their serum low-density lipoprotein cholesterol levels by 23% to 40%. The safety of statins among children is not well known even though statins seem to be safe and well-tolerated in adults.
To assess the effectiveness and safety of statins in children with familial hypercholesterolemia.
Relevant trials were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.
Date of most recent search: 11 March 2010.
Randomized and controlled clinical trials including participants up to 18 years old comparing a statin to placebo or to diet alone.
Data collection and analysis
Two authors independently assessed studies for inclusion and extracted data.
We found 19 potentially eligible studies of which we included eight randomized placebo-controlled trials (897 participants). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points. There was no difference between serum aspartate and alanine aminotransferase or creatine kinase concentrations at any time-point. The risks of myopathy and clinical adverse events were also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilation of the brachial artery, and in another study treatment with pravastatin for two years induced a significant regression in carotid intima-media thickness.
Statin treatment is an efficient lipid-lowering therapy in children with familial hypercholesterolemia. It seems to be safe in the short term but long-term safety is unknown. Children treated with statins should be carefully followed up by their pediatricians. Large long-term randomized controlled trials are needed to establish the long-term safety of statins in children.