title: Efficacy and safety of rosuvastatin therapy in children and adolescents with familial hypercholesterolemia: Results from the CHARON study.
abstract: OBJECTIVE
  Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Guidelines recommend initiating statins early to reduce low-density lipoprotein cholesterol (LDL-C). Studies have evaluated rosuvastatin in children aged ≥10 years, but its efficacy and safety in younger children is unknown.
  
  
  METHODS
  Children with HeFH and fasting LDL-C >4.92 mmol/L (190 mg/dL) or >4.10 mmol/L (>158 mg/dL) with other cardiovascular risk factors received rosuvastatin 5 mg daily. Based on LDL-C targets (<2.85 mmol/L [<110 mg/dL]), rosuvastatin could be uptitrated to 10 mg (aged 6-9 years) or 20 mg (aged 10-17 years). Treatment lasted 2 years. Changes in lipid values, growth, sexual maturation, and adverse events (AEs) were assessed.
  
  
  RESULTS
  The intention-to-treat analysis included 197 patients. At 24 months, LDL-C was reduced by 43, 45, and 35% vs baseline in patients aged 6-9, 10-13, and 14-17 years, respectively (P < .001 for all groups). Most AEs were mild. Intermittent myalgia was reported in 11 (6%) patients and did not lead to discontinuation of rosuvastatin treatment. Serious AEs were reported by 9 (5%) patients, all considered unrelated to treatment by the investigators. No clinically important changes in hepatic biochemistry were reported. Rosuvastatin treatment did not appear to adversely affect height, weight, or sexual maturation.
  
  
  CONCLUSIONS
  In HeFH patients aged 6-17 years, rosuvastatin 5-20 mg over 2 years significantly reduced LDL-C compared with baseline. Treatment was well tolerated, with no adverse effects on growth or sexual maturation.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: J.A.Braamskamp@amc.uva.nl.
authors.forename: Marjet J A M
authors.initials: MJAM
authors.lastname: Braamskamp
authors.affiliation: Lipid Clinic, Oslo University Hospital, Oslo, Norway. Electronic address: glangsle@ous-hf.no.
authors.forename: Gisle
authors.initials: G
authors.lastname: Langslet
authors.affiliation: Department of Pediatrics, Labatt Family Health Center, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Brian W
authors.initials: BW
authors.lastname: McCrindle
authors.affiliation: Department of Hepatology and Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Cassiman
authors.affiliation: Department of Medicine, Healthy Heart Program Prevention Clinic, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Francis
authors.affiliation: Clinique des Maladies Lipidiques de Québec, Québec, QC, Canada.
authors.forename: Claude
authors.initials: C
authors.lastname: Gagné
authors.affiliation: Department of Medicine, Université de Montréal, Chicoutimi, QC, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Morrison
authors.affiliation: Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Wiegman
authors.affiliation: Metabolic & Atherosclerosis Research Center, Cincinnati, OH, USA.
authors.forename: Traci
authors.initials: T
authors.lastname: Turner
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: D Meeike
authors.initials: DM
authors.lastname: Kusters
authors.affiliation: Department of Research and Development, AstraZeneca LP, Wilmington, DE, USA.
authors.forename: Elinor
authors.initials: E
authors.lastname: Miller
authors.affiliation: Department of Research and Development, AstraZeneca LP, Wilmington, DE, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Raichlen
authors.affiliation: Department of Biometrics and Information Sciences, AstraZeneca, Mölndal, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Wissmar
authors.affiliation: Department of Pharmacology, AstraZeneca, Macclesfield, Cheshire, UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Martin
authors.affiliation: Metabolic & Atherosclerosis Research Center, Cincinnati, OH, USA.
authors.forename: Evan A
authors.initials: EA
authors.lastname: Stein
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: John J P
authors.initials: JJP
authors.lastname: Kastelein
mesh_terms: D000293:Adolescent; D002648:Child; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008297:Male; D000068718:Rosuvastatin Calcium / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012449:Safety; D016896:Treatment Outcome
chemical_list: D008078:Cholesterol, LDL; D000068718:Rosuvastatin Calcium
keywords: Children; Heterozygous familial hypercholesterolemia; Low-density lipoprotein cholesterol; Rosuvastatin; Safety; Tolerability