Lovastatin in children with familial hypercholesterolemia – adapted from Pediatrics 1996;97;619-28

Lovastatin in children with familial hypercholesterolemia – adapted from Pediatrics 1996;97;619-28 – Tips from Other Journals

Early identification and treatment of children with primary hyperlipidemia has been advocated as a way to prevent atherosclerosis and consequent coronary heart disease later in life. Familial hypercholesterolemia is an autosomal dominant disorder characterized by elevated total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Current recommendations are to treat children older than 10 years of age with bile acid-binding resins if dietary modification has failed and LDL remains greater than 4.9 mmol per L (190 mg per dL) or if LDL is greater than 4.1 mmol per L (160 mg per dL) in children with a positive family history or with two or more risk factors for cardiac disease. Unfortunately, compliance and control of LDL have been poor even with these measures. Lambert and colleagues conducted a multicenter, randomized, double-blinded trial to assess the efficacy of lovastatin for use in children with familial hypercholesterolemia.

Pediatric male patients with heterozygous familial hypercholesterolemia were included if their LDL levels were above the 95th percentile for age even while on a lipid-lowering diet, if they had failed trials of bile acid-binding resins and if they had a positive family history for coronary heart disease before age 50. Exclusion criteria were concomitant medical conditions such as diabetes mellitus or kidney or liver disorders. Patients who were taking corticosteroid therapy, immunosuppressant therapy or anticonvulsants were also excluded. Patients with types I, III, IV or V hyperlipidemia were also excluded. A complete history and physical examination as well as laboratory tests (including lipid profiles? were performed at baseline and repeated periodically throughout the study. Each patient received placebo for four weeks, and each patient was then randomized to receive either 10, 20, 30 or 40 mg of lovastatin daily for eight weeks. Patients received ophthalmologic examinations at baseline and within eight weeks of completing the study. They continued to follow a standard lipid-lowering diet during the course of the study. Adverse reactions were recorded.

A total of 65 patients completed the study. All four groups had similar characteristics at baseline, including lipid measurements. All doses of lovastatin were found to cause decreases in levels of total cholesterol (decrease: 17 to 29 percent), LDL cholesterol (decrease: 21 to 36 percent) and apolipoprotein B (decrease: 19 to 28 percent). These effects were seen within two weeks and peaked between four and six weeks.

Overall, the greatest effect occurred in the group receiving the 40-mg dose, although this effect was not significantly different from that in the group receiving the 30-mg dose. Compliance with the regimen decreased over time but remained relatively high, with 85 percent of patients taking at least 70 percent of the prescribed pills during the study. No serious adverse effects were noted during the course of the study. Three patients had asymptomatic, spontaneously resolving elevations of creatine kinase levels. Except for changes in plasma cortisol concentrations between placebo and treatment, other blood values were not significantly changed by lovastatin.

The authors conclude that lovastatin therapy is safe and effective in pediatric patients with familial hypercholesterolemia, with monitoring similar to that required in adult patients taking this medication. Long-term studies are needed to verify these findings, but lovastatin shows promise for reducing the risks of hyperlipidemia in children who are genetically predisposed to this disorder. (Lambert M, et al. Treatment of familial hypercholesterolemia in children and adolescents: effect of lovastatin. Pediatrics 1996,97:619-28.)

COPYRIGHT 1996 American Academy of Family Physicians

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