The age at which lipid-lowering drug therapy should be started in patients with familial hypercholesterolemia and premature coronary disease is not well defined, although there is agreement that drug therapy should be started in such patients if a low-fat diet fails to reduce the low-density lipoprotein (LDL) cholesterol level to below 160 mg per dL (4.2 mmol per L). Pharmacologic intervention is also generally advocated in patients without a family history of premature coronary disease if the LDL level remains above 190 mg per dL (4.9 mmol per L). Bile-acid sequestrants, which have a relatively long history of use in children with familial hypercholesterolemia, are generally the drugs of choice, but these agents do not have a major effect on LDL levels. Stein and colleagues conducted a study to determine if a statin (specifically, lovastatin) is safe and effective in the treatment of adolescent males with heterozygous familial hypercholesterolemia.

A total of 132 boys 10 to 17 years of age were enrolled in the double-blind, placebo-controlled study; 110 completed the 48-week study. In all of the boys, LDL levels (despite dietary measures) had measured at least 189 mg per dL (4.9 mmol per L). All of the subjects had a family history of one parent with similarly elevated LDL levels or of a parent who died as a result of coronary artery disease. Tanner stage was assessed at recruitment and at 24 and 48 weeks after study entry. Height, weight, lipid profile, liver function and diet were monitored periodically throughout the study. Dietary instruction was provided.

Lovastatin was started at a dosage of 10 mg per day and increased to 20 mg per day at the eighth week and to 40 mg per day at the 16th week. During the first 24 weeks, while the lovastatin dosage was being gradually increased, LDL and total cholesterol levels dropped in the lovastatin group but not in the placebo group. At 10 mg per day, the mean total cholesterol level declined by 13 percent and the mean LDL level declined by 17 percent. At 20 mg per day, the mean cholesterol and LDL levels dropped by 19 percent and 24 percent, respectively. When the lovastatin dosage was 40 mg per day (in the second 24-week period), the mean total cholesterol level was 20 percent lower than the baseline level, and the mean LDL level was 25 percent lower.

Changes in growth parameters did not differ between the lovastatin group and the placebo group. Alanine aminotransferase (ALT) levels gradually increased in both groups during the study period, but at 48 weeks, the differences were not significant. Aspartate aminotransferase (AST) and creatine kinase values remained unchanged.

The authors conclude that the use of lovastatin in boys with heterozygous familial hypercholesterolemia is both safe and effective. Although the LDL reductions were moderate, evidence suggests that even a modest decrease in adults can slow progression of coronary artery disease and reduce the risk of coronary events.

In a related editorial, Rifkind and associates laud Stein's group for conducting the study, stating that it begins to address concerns about prescribing statins for children with hereditary familial hypercholesterolemia. The editorial also points out some flaws in the study. For example, the safety evaluation failed to study the effects of lovastatin on cognitive and psychosocial function. Issues of compliance were not addressed. That said, the editorial emphasizes that hereditary familial hypercholesterolemia is easily diagnosed and should be treated as aggressively as possible in adolescent boys. The appropriate strategy for girls and young women, given their relatively later onset of clinical coronary heart disease, is less clear.