Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia

Context Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature ath- erosclerotic 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 chil- dren with familial hypercholesterolemia. Design Randomized, double-blind, placebo-controlled trial that recruited children be- tween December 7, 1997, and October 4, 1999, and followed them up for 2 years. Setting and Participants Two hundred fourteen children with familial hypercho- lesterolemia, aged 8 to 18 years and recruited from an academic medical referral cen- ter 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 prava- statin, 20 to 40 mg/d (n=106), or a placebo tablet (n=108). Main Outcome Measures The primary efficacy outcome was the change from base- line 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 pro- gression 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 li- poprotein cholesterol levels compared with placebo (−24.1% vs +0.3%, respectively; P .001). No differences were observed for growth, muscle or liver enzymes, endo- crine function parameters, Tanner staging scores, onset of menses, or testicular vol- ume between the 2 groups. Conclusion Two years of pravastatin therapy induced a significant regression of ca- rotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.
Download het volledige artikel