TY - JOUR
T1 - Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia
AU - Kusters, D. Meeike
AU - Caceres, Maria
AU - Coll, Mauricio
AU - Cuffie, Cynthia
AU - Gagné, Claude
AU - Jacobson, Marc S.
AU - Kwiterovich, Peter O.
AU - Lee, Raymond
AU - Lowe, Robert S.
AU - Massaad, Rachid
AU - McCrindle, Brian W.
AU - Musliner, Thomas A.
AU - Triscari, Joseph
AU - Kastelein, John J.P.
N1 - Funding Information:
Supported by Merck & Co , Inc, Whitehouse Station, NJ. C.G. has participated in clinical trials with AstraZeneca, Pfizer, Merck, Amgen, Regeneron, Sanofi, Genzyme, and Novartis. M.J. has received research grants from Merck . P. K. has received consulting fees/honoraria from Merck and research grants from Abbott Laboratories , GlaxoSmithKline , Merck , and Pfizer . R. M. is an employee of MSD Belgium. B. M. received reimbursement from Merck for participation in this study; serves as a consultant for Bristol Myers Squibb, Eli Lilly, Genzyme, and Janssen; is a DSMB member for Medpace; and participated in a trial sponsored by Astra Zeneca. J. K. has received consulting fees/honoraria from Merck. M. Ca., C. C., R. Le., R. Lo., T. M., and J. T. are employees or former employees of Merck and may own stock/stock options in the company. M. K. and M. Co. declare no conflicts of interest.
Publisher Copyright:
Copyright © 2015 Elsevier Inc. All rights reserved.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Objectives To evaluate the lipid-altering efficacy and safety of ezetimibe monotherapy in young children with heterozygous familial hypercholesterolemia (HeFH) or nonfamilial hypercholesterolemia (nonFH). Study design 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.
AB - Objectives To evaluate the lipid-altering efficacy and safety of ezetimibe monotherapy in young children with heterozygous familial hypercholesterolemia (HeFH) or nonfamilial hypercholesterolemia (nonFH). Study design 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.
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U2 - 10.1016/j.jpeds.2015.02.043
DO - 10.1016/j.jpeds.2015.02.043
M3 - Article
C2 - 25841542
AN - SCOPUS:84930180268
VL - 166
SP - 1377-1384.e3
JO - Journal of Pediatrics
JF - Journal of Pediatrics
SN - 0022-3476
IS - 6
ER -