Statin Therapy in Hypercholesterolemic Children
© 2005 Prime Health Consultants, Inc.
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.
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