Children with heterozygous familial hypercholesterolemia (heFH) are at high risk for developing coronary heart disease. Currently the U.S. National Cholesterol Education Program recommends drug therapy (bile acid sequestrants) in children older than 10 years who have a low-density lipoprotein (LDL) cholesterol level that remains elevated after dietary therapy. De Jongh and associates conducted an international, multicenter, randomized, double-blind, placebo-controlled study of 173 patients to evaluate the efficacy of simvastatin in lowering LDL levels in a large cohort of boys and girls with heFH. The goal of the study was to investigate the safety and tolerability of simvastatin and its influence on growth and pubertal development.

Girls and boys from 10 to 17 years of age who had LDL levels ranging from 158 to 398 mg per dL (4.1 to 10.3 mmol per L) and one parent with a confirmed diagnosis of heFH were included in the study. Persons with homozygous familial hypercholesterolemia and secondary hyperlipidemia were excluded. All subjects had diet therapy and placebo for four weeks before being randomized to treatment with placebo or simvastatin (starting with a daily dosage of 10 mg, which was increased to 20 mg and then to 40 mg). Cholesterol panels, liver function tests, adrenal/gonadal/pituitary hormones, Tanner stages, and menstrual cycles were assessed at regular intervals.

By week 24, the LDL level was reduced 38.4 percent below baseline in the simvastatin group, compared with a 1.2 percent reduction in the placebo group. By week 48, the level was reduced to 40.7 percent below baseline in the simvastatin group, while the placebo group had an increase of 0.3 percent in LDL. Levels of total cholesterol, very-low-density lipoprotein cholesterol, and apolipoprotein B were significantly reduced at all time points. Increases in the levels of high-density lipoprotein and apolipoprotein A and reductions in triglyceride levels were also noted. Few adverse effects occurred during the study, and growth and sexual maturation did not appear to be affected, other than a change in dehydroepiandrosterone sulfate levels in both boys and girls.

The authors acknowledge that other studies have been done on statins in children, including trials with lovastatin, simvastatin, and pravastatin. While the outcomes showed that statins are safe and effective, previous trials were shorter, had fewer patients, and studied mostly boys.