Cochrane Review: Statins for children with familial hypercholesterolemia
Authors: Vuorio Alpo , Kuoppala Jaana , Kovanen Petri T , Humphries Steve E , Strandberg Timo , Tonstad Serena , Gylling Helena 
Published: July 2011

AbstractBackgroundFamilial 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 old. 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 children, so far 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.ObjectivesTo assess the effectiveness and safety of statins in children with familial hypercholesterolemia.Search strategyRelevant trials were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 11 March 2010.Selection criteriaRandomized and controlled clinical trials including participants up to 18 years old comparing a statin to placebo or to diet alone.Data collection and analysisTwo authors independently assessed studies for inclusion and extracted data.Main resultsWe 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 as well as 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.Authors' conclusionsStatin 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.Plain Language SummaryStatins for children with inherited high blood cholesterolFamilial hypercholesterolemia is an inherited disease in which blood cholesterol level is high. Vascular diseases often occur prematurely, especially amongst men. Thus lifelong therapies to reduce blood cholesterol started in childhood are needed. In children with familial hypercholesterolemia, diet has been the main mode of treatment. Resins, such as cholestyramine and colestipol, have also been effective but usually taste unpleasant and are poorly tolerated. Since the 1990s statin trials have been carried out among children and adolescents with familial hypercholesterolemia. Statins have decreased their serum low‐density lipoprotein cholesterol levels by about one third. The safety of statins among children is poorly known, even though statins have seemed to be safe and well‐tolerated in adults.In this review we included randomized and controlled clinical trials with participants up to 18 years old. We found 19 potentially eligible studies, and included eight.Statins reduced the mean low‐density lipoprotein cholesterol concentration on average. The risk of a high increase in liver and muscle enzymes was similar in both the statin and the control groups. Neither was there any clinically important difference in the risk of myopathy nor clinical adverse events between the groups. The follow‐up time on average was only six months, and at longest lasted two years which occurred in one trial only.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.