Early Statin Therapy in Children With Familial Hypercholesterolemia

August 10, 2007 — Follow-up data from a placebo-controlled clinical trial suggests that starting statin therapy early in young patients with familial hypercholesterolemia (FH) significantly delays the progression of atherosclerosis. Investigators showed that statin therapy in patients as young as 8 years old delayed the progression of carotid intima-media thickness (IMT), and they believe the early initiation of treatment could yield large benefits in the prevention of atherosclerosis in adolescence.

"In this longest follow-up study of statin therapy in childhood to date, we demonstrate that, after adjustment for potential confounders, age at statin initiation was positively associated with carotid IMT after follow-up on statin treatment," writes Dr Jessica Rodenburg (Academic Medical Center, Amsterdam, the Netherlands) in the August 7, 2007 issue of Circulation. "This finding indicates that the earlier statin treatment is initiated, the smaller the carotid IMT is later."

FH is characterized by exposure to severely elevated low-density lipoprotein (LDL) cholesterol levels from birth, a condition that predisposes to the early initiation of atherosclerosis. As a result, FH children have been shown to have impaired endothelial function and increased IMT, and myocardial ischemia and coronary artery stenosis have also been documented in these patients. Studies have shown statin therapy to be safe and effective in treating FH children and adolescents, but there are limited long-term data, especially regarding the long-term effects of statins on sexual maturation.

In a previous study, Rodenburg and colleagues showed that 2-year treatment with pravastatin induced a significant regression of carotid IMT in 8- to 18-year-old children with FH. With these data, investigators sought to explore the relationship between the age of statin initiation and carotid IMT after follow-up on statin treatment. All 214 children who participated in the previous placebo-controlled study were eligible for the follow-up study, with all children continuing to take pravastatin 20 mg or 40 mg, depending on their age (children older than 14 years were treated with 40 mg).

Of the 214 original participants, 186 children, with an average treatment duration of 4.5 years, were available for follow-up. Multivariate analysis showed that age at statin initiation was an independent predictor for carotid IMT even after adjusting for carotid IMT at initiation of treatment, sex, and duration of treatment. The earlier initiation of statin therapy was associated with smaller IMT, report the authors.

The data, report Rodenburg and colleagues, support the concept of initiating statin therapy in childhood, a concept that is "further supported by the favorable safety outcomes, which indicate that this therapy had no untoward effects on sexual maturation or growth." Additionally, myopathy was rare, but investigators note that the number of children in the study is not sufficient to appropriately estimate the incidence of adverse events in children on statin treatment.

The investigators write that while statin therapy should be started in children older than eight years, the optimal age at which statin therapy should be initiated is still unknown. Longer-term follow-up of patients who receive early treatment is still needed to confirm the observed benefit, as well as to identify the optimal age for starting therapy. Currently, the American Heart Association recommends diet and lifestyle medications for children with hypercholesterolemia and a statin, if needed, at the lowest possible dose. Lovastatin, simvastatin, pravastatin, and atorvastatin have all received FDA approval for pediatric labeling.

Bristol-Myers Squibb funded the study. According to the paper, coauthor Dr John JP Kastelein (Academic Medical Center) "has received consulting fees, lecture fees, and grant support from Pfizer, Merck, Schering-Plough, AstraZeneca, Bristol-Myers Squibb, and Sankyo." The other authors report they have no disclosures.

Circulation. 2007;116:664-668.

Source: http://www.medscape.com/viewarticle/561230?sssdmh=dm1.293374&src=nldne