Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial

JAMA. 2004 Jul 21;292(3):331-7. doi: 10.1001/jama.292.3.331.


Context: Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention therapy in the causal pathway of this disorder has been available for more than a decade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children.

Objective: To determine the 2-year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia.

Design: Randomized, double-blind, placebo-controlled trial that recruited children between December 7, 1997, and October 4, 1999, and followed them up for 2 years.

Setting and participants: Two hundred fourteen children with familial hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical referral center in the Netherlands.

Intervention: After initiation of a fat-restricted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108).

Main outcome measures: The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 years; the principal safety outcomes were growth, maturation, and hormone level measurements over 2 years as well as changes in muscle and liver enzyme levels.

Results: Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean [SD], -0.010 [0.048] mm; P =.049), whereas a trend toward progression was observed in the placebo group (mean [SD], +0.005 [0.044] mm; P =.28). The mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was significant (P =.02). Also, pravastatin significantly reduced mean low-density lipoprotein cholesterol levels compared with placebo (-24.1% vs +0.3%, respectively; P<.001). No differences were observed for growth, muscle or liver enzymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups.

Conclusion: Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / prevention & control*
  • Child
  • Cholesterol, LDL / blood
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipoproteinemia Type II / drug therapy*
  • Male
  • Pravastatin / adverse effects
  • Pravastatin / therapeutic use*
  • Prospective Studies
  • Ultrasonography


  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pravastatin