van der Graaf Anouk, Cuffie-Jackson Cynthia, Vissers Maud N, Trip Mieke D, Gagné Claude, Shi Genming, Veltri Enrico, Avis Hans J, Kastelein John J P
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
J Am Coll Cardiol. 2008 Oct 21;52(17):1421-9. doi: 10.1016/j.jacc.2008.09.002.
The study evaluated the efficacy and safety of long-term coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia (HeFH).
Aggressive intervention to achieve lipid goals for adolescents with HeFH is recommended to reduce risk of premature cardiovascular disease.
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.
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.
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).
本研究评估依折麦布与辛伐他汀长期联合应用于杂合子家族性高胆固醇血症（HeFH）青少年患者的疗效与安全性。
建议对HeFH青少年患者进行积极干预以实现血脂目标，从而降低过早发生心血管疾病的风险。
在一项多中心、随机、双盲、安慰剂对照研究中，248例年龄≥10岁且≤17岁的HeFH男性和女性受试者被随机分组接受：第1阶段：辛伐他汀10、20或40mg/天加依折麦布10mg/天或安慰剂，为期6周，随后进入第2阶段：辛伐他汀40mg/天加依折麦布10mg/天或安慰剂，为期27周；接着进入第3阶段：所有受试者接受开放标签的辛伐他汀10或20mg/天（滴定至最大40mg/天）加依折麦布10mg/天，为期20周。在整个研究过程中评估安全性。
在联合剂量组和各单独剂量组中，依折麦布与辛伐他汀联合应用6周（第1阶段）导致低密度脂蛋白胆固醇（LDL-C）较基线水平的平均降幅显著大于辛伐他汀单药治疗组（分别为49.5%对比34.4%；p<0.01）（分别为46.7%对比30.4%、49.5%对比34.3%、52.1%对比38.6%；p<0.01）。在33周（第2阶段）时，依折麦布-辛伐他汀组受试者的LDL-C平均降幅为54.0%，而辛伐他汀单药治疗组受试者的平均降幅为38.1%（p<0.01）。在53周（第3阶段）时，LDL-C的总体降幅为49.1%。在整个53周期间，所有治疗方案的耐受性均良好。
在长达53周的HeFH青少年研究中，依折麦布与辛伐他汀联合应用安全、耐受性良好，且与单独使用辛伐他汀相比，能使LDL-C降低更多。（依折麦布与辛伐他汀治疗杂合子家族性高胆固醇血症青少年的疗效；NCT00129402）
