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
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
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.