Starting statin therapy as early as age 8 years may safely and effectively delay the early-onset arterial damage seen in patients with familial hypercholesterolemia, according to an article in the August 7 issue of Circulation.

“Our data support early initiation of statin therapy in familial hypercholesterolemia (FH) children, which might yield a larger benefit in the prevention of atherosclerosis later in life,” said Barbara A. Hutten, PhD, senior author of the study. “In our opinion, physicians should consider statin treatment for all FH children who are 8 or older.”

The disease leads to severely elevated levels of low-density lipoprotein cholesterol, with early thickening of artery walls, premature cardiovascular disease (5 percent by age 30 years; 50 percent by age 50 years), and increased risk of early myocardial infarction.

The disorder also interferes with normal artery function. “Dilation is reduced in children with FH, which reflects an increased stiffness of the vessel wall. This is the first sign of atherosclerosis,” said Hutten, an assistant professor of clinical epidemiology at the University of Amsterdam’s Academic Medical Centre in the Netherlands.

When the researchers began their long-term trial, several previous studies had demonstrated the short-term safety of statins in affected children. However, no study had followed patients for more than 48 weeks.

Researchers enrolled 214 children between ages 8 and 18 years into the single-center, randomized, double-blind, placebo-controlled study at the Academic Medical Centre. Participants were admitted if they had one parent with a clinical or molecular diagnosis and met other criteria, including elevated levels of low-density cholesterol.

Children were randomized to pravastatin or placebo for two years. Those younger than 14 years received 20 mg daily, while those 14 or older received a 40-mg dose. At the end of the two years, the pravastatin-treated group continued taking the drug and the placebo group switched to pravastatin.

To assess effectiveness, the team used ultrasound to measure intima media thickness (IMT) in the carotid artery.

“Carotid IMT is widely accepted as a standardized and validated surrogate marker for atherosclerotic vascular disease,” said Maud N. Vissers, PhD, co-author of the study.

In 2004, the team reported that two years of therapy had reduced the progression of atherosclerosis in the pravastatin group compared with the placebo group.

The current analysis reflects findings from 186 of the original participants - 96 who had started on pravastatin and 90 from the placebo group. These patients received pravastatin for between 2.1 and 7.4 years (average, 4.5 years).

The children were an average 13.7 years old at enrollment; 49 percent were male. After all patients were taking the statin, 83 percent continued pravastatin and 17 percent switched to another statin.

Analyses of 4.5-year data showed that the age of statin initiation was a strong, independent predictor for increased intima-media thickening. This held true even after adjustment for gender, intima-media thickness when treatment began, and duration of statin therapy.

The researchers projected that artery wall thickening would increase 0.003 mm for each year that statin therapy was delayed.

“The results show that earlier initiation of statin treatment results in a smaller carotid IMT at a later age,” said John J. P. Kastelein, MD, PhD, co-author of the study. “However, each child will differ with respect to the family history, lipid profile, other risk factors, or lifestyle. To decide whether or not to start treatment, physicians should balance benefit and risk based on the personal situation of each individual child.”

None of the children in the study suffered increases in liver or muscle enzymes attributed to medication. Two boys had temporary increases in muscle enzymes apparently related to extreme physical exercise. Four patients complained of muscle pain but had no elevated muscle enzymes, Hutten said.

During the average 4.5 years of follow-up, “no serious clinical or laboratory adverse events were reported, as well as any untoward effects on sexual maturation or growth,” Kastelein said. “However, the number of children in our study is not sufficient to appropriately estimate the incidence of adverse events in children on statin treatment.”

Optimal age for beginning statin therapy in FH children remains unknown and will require further clinical trials to resolve, Vissers said. “We intend to continue to monitor the children in our study as long as possible.”