de Jongh Saskia, Ose Leiv, Szamosi Tamás, Gagné Claude, Lambert M, Scott Russell, Perron P, Dobbelaere Dries, Saborio M, Tuohy Mary B, Stepanavage Michael, Sapre Aditi, Gumbiner Barry, Mercuri Michele, van Trotsenburg A S Paul, Bakker Henk D, Kastelein John J P
Department of Vascular Medicine, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Circulation. 2002 Oct 22;106(17):2231-7. doi: 10.1161/01.cir.0000035247.42888.82.
A multicenter, randomized, double-blind, placebo-controlled study was conducted to evaluate LDL cholesterol-lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia (heFH).
A total of 173 heFH children (98 boys and 75 girls) were included in this study. After a 4-week diet/placebo run-in period, children with heFH were randomized to either simvastatin or placebo in a ratio of 3:2. Simvastatin was started at 10 mg/d and titrated at 8-week intervals to 20 and then 40 mg/d. During a 24-week extension period, the patients continued to receive simvastatin (40 mg) or placebo according to their assignment. After 48 weeks of simvastatin therapy, there were significant reductions of LDL cholesterol (-41%), total cholesterol (-31%), apolipoprotein B (-34%), VLDL cholesterol (-21%), and triglyceride (-9%) levels. HDL cholesterol and apolipoprotein A-I levels were increased by 3.3% and 10.4%, respectively (not significant). No safety issues became evident. Except for small decreases in dehydroepiandrosterone sulfate compared with placebo, there were no significant changes from baseline in adrenal, gonadal, and pituitary hormones in either treatment group.
Simvastatin significantly reduced LDL cholesterol, total cholesterol, triglyceride, VLDL cholesterol, and apolipoprotein B levels and was well tolerated in children with heFH. There was no evidence of any adverse effect of simvastatin on growth and pubertal development. Therefore, simvastatin at doses up to 40 mg is a well-tolerated and effective therapy for heFH children.
开展了一项多中心、随机、双盲、安慰剂对照研究，以评估辛伐他汀对一大群杂合子家族性高胆固醇血症（heFH）男孩和女孩的降低低密度脂蛋白胆固醇疗效、总体安全性和耐受性以及对生长和青春期发育的影响。
本研究共纳入173例heFH儿童（98例男孩和75例女孩）。经过4周的饮食/安慰剂导入期后，heFH儿童按3:2的比例随机分为辛伐他汀组或安慰剂组。辛伐他汀起始剂量为10mg/d，每8周递增至20mg/d，然后为40mg/d。在24周的延长期内，患者根据分组继续接受辛伐他汀（40mg）或安慰剂治疗。辛伐他汀治疗48周后，低密度脂蛋白胆固醇（-41%）、总胆固醇（-31%）、载脂蛋白B（-34%）、极低密度脂蛋白胆固醇（-21%）和甘油三酯（-9%）水平显著降低。高密度脂蛋白胆固醇和载脂蛋白A-I水平分别升高了3.3%和10.4%（无显著性差异）。未发现明显的安全问题。与安慰剂相比，除硫酸脱氢表雄酮略有下降外，两个治疗组的肾上腺、性腺和垂体激素水平与基线相比均无显著变化。
辛伐他汀显著降低了heFH儿童的低密度脂蛋白胆固醇、总胆固醇、甘油三酯、极低密度脂蛋白胆固醇和载脂蛋白B水平，且耐受性良好。没有证据表明辛伐他汀对生长和青春期发育有任何不良影响。因此，高达40mg剂量的辛伐他汀是治疗heFH儿童耐受性良好且有效的疗法。
