CHARON: Rosuvastatin effective, safe in children with familial hypercholesterolemia
Two years of treatment with rosuvastatin 5 mg to 20 mg was associated with significant reductions in LDL and was well tolerated in patients younger than 17 years with heterozygous familial hypercholesterolemia.
The safety and efficacy of rosuvastatin has been studied in adults and children older than 10 years with heterozygous familial hypercholesterolemia (HeFH), but little is known about its effects on younger children, researchers wrote in the Journal of Clinical Lipidology.
Marjet J.A.M. Braamskamp, MD , and researchers for the CHARON trial enrolled 197 children with HeFH and fasting LDL of more than 190 mg/dL (4.92 mmol/L) or more than 158 mg/dL (4.1 mmol/L) plus other CV risk factors. Participants received a starting dose of rosuvastatin (Crestor, AstraZeneca) 5 mg daily. The dose was uptitrated in 3-month intervals up to 10 mg for children aged 6 to 9 years and up to 20 mg for children and adolescents aged 10 to 17 years, based on LDL targets (< 110 mg/dL [2.85 mmol/L]). Adverse events, changes in lipid values, and growth and puberty changes were measured for each participant.
According to results of the intention-to-treat analysis, at 2 years, the mean reduction in LDL was 43% among participants aged 6 to 9 years, 45% among participants aged 10 to 13 years and 35% among patients aged 14 to 17 years (P < .001 for all).
“A possible explanation [for the difference in reduction in the older group] may be because of differences in the distribution and expression of transporters involved in the uptake of rosuvastatin between younger, smaller children and older, larger children,” the researchers wrote.
The researchers also observed significant reductions in total cholesterol, non-HDL and apolipoprotein B (P < .001 for all) and a significant rise in HDL (P .001).
Additionally, 58% of participants reached an LDL goal of less than 130 mg/dL (< 3.36 mmol/L) and 38% reached a goal of less than 110 mg/dL (< 2.85 mmol/L).
The rate of adverse events was 88% in participants aged 6 to 9 years, 86% in participants aged 10 to 13 years and 89% in participants aged 14 to 17 years. Most adverse events were mild and included common cold, headache, influenza and vomiting. Fifteen percent of participants experienced adverse events that were potentially related to treatment; of those, 8% were gastrointestinal disorders, 2% muscle pain, 1% skin disorders and 1% increased blood creatine kinase. Three participants stopped treatment due to nausea, migraines and paresthesia. Only 5% of participants developed serious adverse events, and these were not related to treatment, according to the researchers.
Rosuvastatin did not affect changes in height, weight or sexual maturation, according to the findings.
“To our knowledge, this is the longest study to date to evaluate the efficacy and safety of rosuvastatin in children and adolescents aged 6 to 17 years with HeFH. Concern may still remain, however, about the safety of statins in children, particularly young children. ... Future studies should consider monitoring the safety of statins over an even longer period of time to fully establish the safety of statins in this population,” the researchers concluded. – by Tracey Romero
Disclosure: The CHARON study was funded by AstraZeneca. Please see the full study for a list of the authors’ relevant financial disclosures.