MADRID, SPAIN — Treatment with rosuvastatin (Crestor, AstraZeneca) for two years appears to slow the progression of subclinical atherosclerosis in children and adolescents with heterozygous familial hypercholesterolemia (FH), a new study shows[1].

Compared with healthy siblings who were unaffected with FH, the mean carotid intima-media thickness (IMT) was significantly higher among those with heterozygous FH prior to starting rosuvastatin. After two years of treatment with the statin, however, there was no longer any difference in mean carotid IMT between the healthy controls and affected children and adolescents.

The results, which were presented by Dr Marjet Braamskamp (Academic Medical Center, Amsterdam, the Netherlands) here at the European Atherosclerosis Society 2014 Congress (EAS 2014), suggest that treatment with the cholesterol-lowering drug is altering the progression of atherosclerosis, say investigators.

The Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin (METEOR) study, published in 2007, has previously shown that treating low-risk patients—those with a Framingham risk score of less than 10%—with rosuvastatin slowed the progression of carotid IMT compared with placebo. The METEOR study, however, included asymptomatic middle-aged adults with modestly elevated LDL-cholesterol levels. Whether or not the drug can slow the progression in a high-risk cohort of young patients affected with FH is unknown, said Braamskamp.

"These children have increased LDL-cholesterol levels from birth onward," she said. "Studies have shown that from the age of 10 years, they have significantly increased carotid IMT compared with their unaffected siblings."

Rosuvastatin, to date, has not been tested in children younger than 10 years of age, yet the current clinical guidelines for the management of patients with FH state that children should be treated from age eight years onward to prevent the early onset of atherosclerosis.

With this in mind, the group performed the CHARON study, in which 196 children and adolescents aged six to 17 years of age were randomly assigned to rosuvastatin. For those aged six to nine years, rosuvastatin 5 mg was used with the goal to increase the dose to 10 mg once daily. For those aged 10 to 17 years, 20 mg was used if the patient was unable to achieve a treatment target of LDL less than 110 mg/dL with the 10-mg dose. For the comparator, 65 unaffected siblings served as the control arm. The mean age at baseline was 11 years, and the mean LDL-cholesterol level prior to treatment was 236 mg/dL in the kids with FH.

At baseline, the mean carotid IMT measurement was 0.398 mm in the patients with FH and 0.376 mm in the control arm, a statistically significant difference. By 12 months, however, the difference in the mean carotid IMT was no longer statistically significant. After stratification by patient age—six to nine years, 10 to 13 years, and 14 to 17 years—the slowed progression of subclinical atherosclerosis was observed in all groups.

Mean Carotid IMT (mm) at Baseline, 12 Months, and 24 Months

Visit FH Children (n=196) Control (n=65)
Baseline mean carotid IMT* 0.398 0.376
12-month mean carotid IMT 0.402 0.390
24-month mean carotid IMT 0.409 0.402
*p≤0.001 for FH vs control arm

Regarding the safety and efficacy of rosuvastatin in this population, Braamskamp presented data in a second session detailing the reductions in LDL cholesterol with the drug[2]. At three months, rosuvastatin reduced LDL-cholesterol levels 38% in the treated children and adolescents. At 12 and 24 months, the reductions in LDL cholesterol were 44% and 43%, respectively. For the youngest children, those aged six to nine years, the reduction in LDL cholesterol at 12 and 24 months was identical to the reductions achieved in the overall cohort (44% and 43%, respectively).

After two years, 38% of the participants met the guideline-recommended target of LDL cholesterol less than 110 mg/dL. For those aged six to nine years, 10 to 13 years, and 14 to 17 years, 38%, 46%, and 28%, respectively, achieved the LDL-cholesterol target of less than 110 mg/dL.

More than 85% of the kids reported adverse events, including headaches, nasopharyngitis, and influenzalike symptoms, but Braamskamp said these were considered mild by the investigators. In total, three patients discontinued therapy because of adverse events (nausea, migraine, and paraesthesia).

Finally, the investigators reported height and weight data, noting that all patients remained within the normal range for their age. More than 80% of patients grew when their physical and sexual development was measured by using the Tanner scale, a conventional measure that assesses growth in children and adolescents.

The CHARON study was sponsored by AstraZeneca. Braamskamp reports no conflicts of interest. Other members of the CHARON study report consulting for and/or receiving grant support from AstraZeneca, among other pharmaceutical companies.

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