Statins for children with inherited high blood cholesterol

Review question

We reviewed the evidence for the effectiveness and safety of statins in children with inherited high blood cholesterol.


Familial hypercholesterolemia is an inherited disease in which the blood cholesterol level is high. Vascular disease, i.e. furring up of the blood vessels, often occurs at an earlier age than usual, especially amongst men. Thus lifelong therapies, started in childhood, to reduce blood cholesterol are needed. In children with familial hypercholesterolemia, diet has been the main treatment option. Medications, such as cholestyramine and colestipol, have been used effectively, but due to their unpleasant taste they are poorly tolerated and treatment plans are not followed. The advent of statin therapy for children has improved treatment and this review updates the previous published version.

Search date

The evidence is current to: 04 November 2019.

Study characteristics

The review included 9 studies with 1177 people with heterozygous familial hypercholesterolemia aged between 4 and 18 years of age. Studies compared different statin treatments with a substance which contains no medication (termed placebo) and people were selected for one treatment or the other randomly. The studies lasted from 12 weeks to 104 weeks.

Key results

In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins probably reduced the mean low-density lipoprotein cholesterol concentration at all time points (high-quality evidence). The levels of the liver enzymes, serum aspartate and alanine aminotransferase, and the muscle enzyme, creatinine kinase, did not differ between treated and placebo groups at any time point (low-quality evidence). The risks of myopathy (disease of muscle tissue) and side-effects were very low and similar in both groups (low-quality evidence). Two of the statins, simvastatin and pravastatin may have a positive effect on two of the major blood vessels typically affected by raised cholesterol levels (low-quality evidence).

Quality of the evidence

Information regarding blinding (performance bias and detection bias), was available for all nine studies; each was described as double blind, indicating that participants and those participating in treatment procedures were blinded to treatment. In two studies information on how the participants were allocated to treatment groups (selection bias) was clearly presented, but this information was not clearly stated in the remaining seven studies. There is a lack of information whether investigators knew which treatment group participants would be put into (selection bias) and or whether selective reporting (reporting bias) occurred, but it is very unlikely. In conclusion, it can be stated all the studies appeared to be well run and we do not think any of the above-mentioned factors influenced the results in a negative way. Quality of evidence varied from high (change in serum low-density lipoprotein (LDL) cholesterol) through moderate (adverse events) to low (change in blood vessel wall (carotid intima-media) thickness, change in measures if growth and maturation, liver dysfunction, myopathy and change in blood wall (endothelial) function).

Authors' conclusions: 

Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. Few or no 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.

Read the full abstract...

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.


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

Search strategy: 

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

Date of most recent search: 04 November 2019.

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 (high-quality evidence). There may be little or no difference in liver function (serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations) between treated and placebo groups at any time point (low-quality evidence). There may be little or no difference in myopathy (as measured in change in creatinine levels) (low-quality evidence) or clinical adverse events (moderate-quality evidence) with statins compared to placebo. One study on simvastatin showed that this may slightly improve flow-mediated dilatation of the brachial artery (low-quality evidence), and on pravastatin for two years may have induced a regression in carotid intima media thickness (low-quality evidence).

No studies reported rhabdomyolysis (degeneration of skeletal muscle tissue) or death due to rhabdomyolysis, quality of life or compliance to study medication.