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Intervention Review

Statins for children with familial hypercholesterolemia

  1. Alpo Vuorio1,*,
  2. Jaana Kuoppala2,
  3. Petri T Kovanen3,
  4. Steve E Humphries4,
  5. Timo Strandberg5,
  6. Serena Tonstad6,
  7. Helena Gylling7

Editorial Group: Cochrane Cystic Fibrosis and Genetic Disorders Group

Published Online: 7 JUL 2010

Assessed as up-to-date: 3 JUN 2010

DOI: 10.1002/14651858.CD006401.pub2


How to Cite

Vuorio A, Kuoppala J, Kovanen PT, Humphries SE, Strandberg T, Tonstad S, Gylling H. Statins for children with familial hypercholesterolemia. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD006401. DOI: 10.1002/14651858.CD006401.pub2.

Author Information

  1. 1

    Mehilainen Airport Medical Center, Vantaa, Finland

  2. 2

    Kiiskilampi, Finland

  3. 3

    Wihuri Research Institute, Helsinki, Finland

  4. 4

    BHF Laboratories, Royal Free and University College Medical School, Center for Cardiovascular Genetics, London, UK

  5. 5

    University of Oulu & Oulu University Hospital, Unit of General Practice, Department of Health Sciences/Geriatrics, Oulu, Finland

  6. 6

    Ullevål University Hospital, Dept. of Preventive Cardiology, Olso, Norway

  7. 7

    University of Kuopio & Kuopio University Central Hospital, Department of Clinical Nutrition, Kuopio, Finland

*Alpo Vuorio, Mehilainen Airport Medical Center, Vantaa, Finland. alpo.vuorio@gmail.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 7 JUL 2010

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary

Background

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.

Objectives

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

Search methods

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

Date of most recent search: 11 March 2010.

Selection criteria

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.

Main results

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.

Authors' conclusions

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.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary

Statins for children with inherited high blood cholesterol

Familial 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. Additionally, in one study, statin treatment improved the arterial function and in another study statin treatment reduced the thickness of the already thickened neck artery. 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.