Background

Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low‐density lipoprotein cholesterol levels 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 treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid‐lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low‐density lipoprotein cholesterol levels. While statins seem to be safe and well‐tolerated in children, their long‐term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review.

Objectives

To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia.

Search methods

Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.

Date of most recent search: 20 February 2017.

Selection criteria

Randomized and controlled clinical studies 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.

Main results

We found 26 potentially eligible studies, of which we included nine randomized placebo‐controlled studies (1177 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 low‐density lipoprotein cholesterol concentration at all time points (moderate quality evidence). Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point (low quality evidence). The risks of myopathy (low quality evidence) and clinical adverse events (moderate quality evidence) were very low and also similar in both groups. In one study simvastatin was shown to improve flow‐mediated dilatation of the brachial artery (low quality evidence), and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness (low quality evidence).

Authors' conclusions

Statin treatment is an effective 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 remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long‐term randomized controlled trials are needed to establish the long‐term safety issues of statins.