Familial hypercholesterolemia is an inherited disease in which blood cholesterol level is high. Vascular diseases often occur at an earlier age than usual, 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 treatment option. Resins, such as cholestyramine and colestipol, have also been used effectively to lower low-density lipoprotein (LDL) cholesterol. However, these usually taste unpleasant and are poorly tolerated; so they are poorly adhered to. Since the 1990s statin trials have been carried out among children and adolescents with familial hypercholesterolemia. Statins have decreased their serum LDL cholesterol levels by about one third in these studies. Additionally, in one study, statins improved the arterial function and in another study they reduced the thickness of the already thickened neck artery. Even though statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established.
In this review we included randomized and controlled clinical trials with participants up to 18 years old. We included eight out of the 22 potentially eligible studies identified. The average follow-up time was only six months, and the longest follow up was for two years (one study only), with an extension without a control group up to five years.
Statins reduced the mean LDL cholesterol concentration on average by 23% to 40%. Only rarely was there the risk of a high increase in liver and muscle enzymes and this risk was similar in both the statin and the control groups. There were no clinically important differences in the risk of myopathy or clinical adverse events between the groups.
Statin treatment is an efficient lipid-lowering therapy in children with familial hypercholesterolemia. Statins seem to be safe in the short term but long-term safety is unknown.
Statin treatment is an efficient lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety is unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians or physicians into adulthood. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.
Familial hypercholesterolemia is one of the most common inherited metabolic diseases; the average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500. Diagnosis of familial hypercholesterolemia in children is based on highly elevated low-density lipoprotein (LDL) cholesterol level or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong hypolipidemic measures, started in childhood, are needed to reduce the risk of cardiovascular disease. In children with familial hypercholesterolemia, diet is as yet the cornerstone of treatment. Anion exchange resins, such as cholestyramine and colestipol, have also been found to be effective, but are poorly tolerated. Since the 1990s statin studies have been carried out among children with familial hypercholesterolemia (aged 7 to 17 years). Statins greatly reduced their serum LDL cholesterol levels. Even though statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established.
To assess the effectiveness and safety of statins in children with familial hypercholesterolemia.
Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.
Date of most recent search: 14 October 2013.
Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone.
Two authors independently assessed studies for inclusion and extracted data.
We found 21 potentially eligible studies, of which we included eight randomized placebo-controlled studies (1074 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean LDL cholesterol concentration at all time points. Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point. The risks of myopathy and clinical adverse events were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery, and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness.