OBJECTIVES: The study evaluated the efficacy and safety of long-term coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia (HeFH). BACKGROUND:Aggressive intervention to achieve lipid goals for adolescents with HeFH is recommended to reduce risk of premature cardiovascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled study, 248 male and female subjects ages >or=10 and <or=17 years with HeFH were randomized to receive: step 1: simvastatin 10, 20, or 40 mg/day plus ezetimibe 10 mg/day or placebo for 6 weeks, followed by step 2: simvastatin 40 mg/day plus ezetimibe 10 mg/day or placebo for 27 weeks; followed by step 3: all subjects received open-label simvastatin 10 or 20 mg/day (titrated to maximum 40 mg/day) plus ezetimibe 10 mg/day for 20 weeks. Safety was assessed throughout the study. RESULTS:Coadministered ezetimibe and simvastatin for 6 weeks (step 1) resulted in significantly greater mean reduction in low-density lipoprotein cholesterol (LDL-C) from baseline (49.5%) compared with simvastatin monotherapy (34.4%; p < 0.01) in pooled dose groups and in individual dose groups (46.7% vs. 30.4%, 49.5% vs. 34.3%, 52.1% vs. 38.6%, respectively; p < 0.01). At 33 weeks (step 2), ezetimibe-simvastatin subjects had a mean 54.0% reduction in LDL-C compared with a mean 38.1% reduction in simvastatin monotherapy subjects (p < 0.01). At 53 weeks (step 3), the pooled reduction in LDL-C was 49.1%. All treatment regimens were well tolerated throughout 53 weeks. CONCLUSIONS: Coadministration of ezetimibe with simvastatin was safe, well tolerated, and provided higher LDL-C reduction compared with simvastatin alone in adolescents with HeFH studied up to 53 weeks. (Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With Heterozygous Familial Hypercholesterolemia; NCT00129402).
RCT Entities:
OBJECTIVES: The study evaluated the efficacy and safety of long-term coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia (HeFH). BACKGROUND: Aggressive intervention to achieve lipid goals for adolescents with HeFH is recommended to reduce risk of premature cardiovascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled study, 248 male and female subjects ages >or=10 and <or=17 years with HeFH were randomized to receive: step 1: simvastatin 10, 20, or 40 mg/day plus ezetimibe 10 mg/day or placebo for 6 weeks, followed by step 2: simvastatin 40 mg/day plus ezetimibe 10 mg/day or placebo for 27 weeks; followed by step 3: all subjects received open-label simvastatin 10 or 20 mg/day (titrated to maximum 40 mg/day) plus ezetimibe 10 mg/day for 20 weeks. Safety was assessed throughout the study. RESULTS: Coadministered ezetimibe and simvastatin for 6 weeks (step 1) resulted in significantly greater mean reduction in low-density lipoprotein cholesterol (LDL-C) from baseline (49.5%) compared with simvastatin monotherapy (34.4%; p < 0.01) in pooled dose groups and in individual dose groups (46.7% vs. 30.4%, 49.5% vs. 34.3%, 52.1% vs. 38.6%, respectively; p < 0.01). At 33 weeks (step 2), ezetimibe-simvastatin subjects had a mean 54.0% reduction in LDL-C compared with a mean 38.1% reduction in simvastatin monotherapy subjects (p < 0.01). At 53 weeks (step 3), the pooled reduction in LDL-C was 49.1%. All treatment regimens were well tolerated throughout 53 weeks. CONCLUSIONS: Coadministration of ezetimibe with simvastatin was safe, well tolerated, and provided higher LDL-C reduction compared with simvastatin alone in adolescents with HeFH studied up to 53 weeks. (Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With Heterozygous Familial Hypercholesterolemia; NCT00129402).
Authors: David I Feldman; Michael J Blaha; Raul D Santos; Steve R Jones; Roger S Blumenthal; Peter P Toth; Laurence S Sperling; Seth S Martin Journal: Curr Atheroscler Rep Date: 2015-01 Impact factor: 5.113
Authors: Robert A Hegele; Samuel S Gidding; Henry N Ginsberg; Ruth McPherson; Frederick J Raal; Daniel J Rader; Jennifer G Robinson; Francine K Welty Journal: Arterioscler Thromb Vasc Biol Date: 2015-09-16 Impact factor: 8.311