摘要
背景:在家族性高胆固醇血症儿童当中,可以见到有血管内皮功能紊乱和颈总动脉内膜中层厚度(IMT) 增加的情况,这是动脉粥样硬化性疾病的早期征兆。虽然针对这一发病原因的预防性治疗已经有10年的历史,但是对儿童进行低胆固醇药物治疗的长期效果和安全性进行评估尚未有报道。目的:本文对应用普伐他汀治疗家族性高胆固醇血症儿童2年期的疗效和安全性进行观察评估。方法:设计采用随机、双盲、安慰剂对照试验。
Context: Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention therapy in the causal pathway of this disorder has been available for more than a decade, the long-term efficacy and safety of cholesterol-lowering medication have not been . evaluated in children. Objective: To determine the 2 -year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia. Design: Randomized, double-blind, placebo-controlled trial that recruited children between December 7, 1997, and October 4, 1999, and followed them up for 2 years. Setting and Participants: Two hundred fourteen children with familial hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical referral center in the Netherlands. Intervention: After initiation of a fat-restricted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n=106), or a placebo tablet (n = 108) . Main Outcome Measures: The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 years; the principal safety outcomes were growth, maturation, and hormone level measurements over 2 years as well as changes in muscle and liver enzyme levels. Results: Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean [SD], -0.010 [0.048] mm; P =. 049), whereas a trend toward progression was observed in the placebo group (mean [SD], +0.005 [0. 044] mm; P = . 28) . The mean (SD) change in IMT compared between the 2 groups (0. 014 [0. 046] mm) was significant (P = .02) . Also, pravastatin significantly reduced mean low-density lipoprotein cholesterol levels compared with placebo ( -24. 1% vs +0. 3%, respectively; P< .001) . No differences were observed for growth, muscle or liver enzymes, endocrine function parameters, Tanner staging scores, onset of menses, or tes-ticular volume between the 2 groups. Conclusion: Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hyperc-holesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.
