title: Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia.
abstract: OBJECTIVE
  To evaluate the lipid-altering efficacy and safety of ezetimibe monotherapy in young children with heterozygous familial hypercholesterolemia (HeFH) or nonfamilial hypercholesterolemia (nonFH).
  
  
  METHODS
  One hundred thirty-eight children 6-10 years of age with diagnosed HeFH or clinically important nonFH (low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL [4.1 mmol/L]) were enrolled into a multicenter, 12-week, randomized, double-blind, placebo-controlled study. Following screening/drug washout and a 5-week single-blind placebo-run-in with diet stabilization, subjects were randomized 2:1 to daily ezetimibe 10 mg (n = 93) or placebo (n = 45) for 12 weeks. Lipid-altering efficacy and safety were assessed in all treated patients.
  
  
  RESULTS
  Overall, mean age was 8.3 years, 57% were girls, 80% were white, mean baseline LDL-C was 228 mg/dL (5.9 mmol/L), and 91% had HeFH. After 12 weeks, ezetimibe significantly reduced LDL-C by 27% after adjustment for placebo (P < .001) and produced significant reductions in total cholesterol (21%), nonhigh-density lipoprotein cholesterol (26%), and apolipoprotein B (20%) (P < .001 for all). LDL-C lowering response in sex, race, baseline lipids, and HeFH/nonFH subgroups was generally consistent with overall study results. Ezetimibe was well tolerated, with a safety profile similar to studies in older children, adolescents, and adults.
  
  
  CONCLUSIONS
  Ezetimibe monotherapy produced clinically relevant reductions in LDL-C and other key lipid variables in young children with primary HeFH or clinically important nonFH, with a favorable safety/tolerability profile.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00867165.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: D.M.Kusters@amc.uva.nl.
authors.forename: D Meeike
authors.initials: DM
authors.lastname: Kusters
authors.affiliation: Merck and Co, Inc, Whitehouse Station, NJ.
authors.forename: Maria
authors.initials: M
authors.lastname: Caceres
authors.affiliation: Centro Almirante Colon, Bogota, Colombia.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Coll
authors.affiliation: Merck and Co, Inc, Whitehouse Station, NJ.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cuffie
authors.affiliation: La Clinique des Maladies Lipidiques de Quebec, Inc, Quebec, Quebec, Canada.
authors.forename: Claude
authors.initials: C
authors.lastname: Gagné
authors.affiliation: ProHealth Care Associates, New York, NY.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Jacobson
authors.affiliation: The Johns Hopkins University, Baltimore, MD.
authors.forename: Peter O
authors.initials: PO
authors.lastname: Kwiterovich
authors.affiliation: Merck and Co, Inc, Whitehouse Station, NJ.
authors.forename: Raymond
authors.initials: R
authors.lastname: Lee
authors.affiliation: Merck and Co, Inc, Whitehouse Station, NJ.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lowe
authors.affiliation: MSD Belgium, Brussels, Belgium.
authors.forename: Rachid
authors.initials: R
authors.lastname: Massaad
authors.affiliation: The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Brian W
authors.initials: BW
authors.lastname: McCrindle
authors.affiliation: Merck and Co, Inc, Whitehouse Station, NJ.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Musliner
authors.affiliation: Merck and Co, Inc, Whitehouse Station, NJ.
authors.forename: Joseph
authors.initials: J
authors.lastname: Triscari
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004311:Double-Blind Method; D000069438:Ezetimibe; D005260:Female; D006579:Heterozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D000069438:Ezetimibe