Efficacy and Safety of Statin Therapy in Children With Familial Hypercholesterolemia: A Randomized Controlled Trial

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