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Wiegman and
associates report findings of a 2-year randomized placebo-controlled
efficacy and safety trial of pravastatin for the treatment of
familial hypercholesterolemia in children ages 8 to 18 years. Two
hundred fourteen children (100 boys), mean age 13.0 years, were
studied. Inclusion criteria were: one parent with a definite clinical
or molecular diagnosis of familial hypercholesterolemia; at least 3
months on a fat-restricted diet (<30% of total calories from fat,
10% saturated fat); 2 fasting LDL-C levels of at least 155mg/dL; no
current drug treatment or use of plant sterols. The primary efficacy
variable was change from baseline of carotid intimamedia thickness
(IMT) as measured by ultrasound. Blood samples were measured for
total cholesterol, HDL-C, LDL-C and triglycerides at 3–6 month
intervals over the 2-year study. In addition, ALT, AST, and CPK were
measured for safety reasons, and levels of sex steroids,
gonadotropins, cortisol, and TSH were determined to survey for
potential side effects of the drug on growth and sexual development.
Height and weight were measured and Tanner staging was performed at
baseline, 1, and 2 years.
Baseline
characteristics were similar in both groups. The mean carotid IMT was
attenuated after 2 years of treatment, while there was a trend
towards an increase in the placebo group. The overall change between
the 2 groups was statistically significant. LDL-C levels were reduced
in the treatment group, while HDL-C, triglyceride and lipoprotein(a)
levels remained unchanged. All hormone levels (corticotropin,
cortisol, LH, FSH, DHEA-S, TSH, estradiol, testosterone) were similar
in both groups at 2 years. Height and weight increased similarly in
both groups, as did stages of sexual development. AST, ALT, and CPK
levels were also similar, although one child in the placebo group had
an asymptomatic but marked increase in CPK, which returned to normal.
The authors point out
that this is the first long-term safety and efficacy trial of a
3-hydroxyl-3 methylglutaryl coenzyme A reductase inhibitor (statin)
in children with familial hypercholesterolemia. The drug was both
effective and well tolerated with minimal observable side effects.
There were no effects on growth or sexual development. Despite these
encouraging findings, they caution that even longer studies are
needed to establish the safety of this class of drugs.
Wiegman
A, Hutten B, de Groot E, et al. Efficacy and safety of statin therapy
in children with familial hypercholesterolemia: a randomized
controlled trial. JAMA 2004;292: 331-7.
Editor’s
Comment: This is a welcomed study. Although the efficacy of
statins in reducing LDL-C has been reported in several studies, this
safety study is reassuring. More and more frequently pediatric
endocrinologists are faced with younger and younger children with
obesity and hypercholesterolemia, or diabetes and
hypercholesterolemia, and need to recommend effective and safe
therapy. Diet and exercise, unfortunately, are rarely practiced with
sufficient adherence to be considered effective and realistic
treatment options. Furthermore, resins are poorly tolerated in this
age group. The use of statins is therefore an obvious therapeutic
choice, but information regarding their long-term safety and side
effects has been lacking. We would encourage these authors to
continue their study of these children with the anticipation that
further data will establish safety over an even longer time period.
William L. Clarke, MD
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Current GGH - Vol. 24 No. 1
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