Wiegman Albert, Ruzza Andrea, Hovingh G Kees, Santos Raul D, Mach François, Stefanutti Claudia, Luirink Ilse K, Bridges Ian, Wang Bei, Bhatia Ajay K, Raal Frederick J, Kastelein John J P, Gaudet Daniel
Department of Paediatrics, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.
Amgen Inc., Thousand Oaks, CA, USA.
Eur J Prev Cardiol. 2024 Nov 12. doi: 10.1093/eurjpc/zwae369.
Children with heterozygous familial hypercholesterolaemia (HeFH) show greater carotid intima-media thickness (cIMT). Evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody, substantially reduced low-density lipoprotein cholesterol (LDL-C) and modestly reduced lipoprotein(a) in children with HeFH. We investigated evolocumab's effect on cIMT progression.
HAUSER-RCT was a randomised, placebo-controlled trial. 157 paediatric patients with FH (age: 10-17 years) and LDL-C >130mg/dL despite statin therapy received monthly evolocumab 420mg or placebo for 24 weeks. Patients who continued into an open-label extension (HAUSER-OLE; n=150) received 80 weeks of monthly evolocumab plus statins. cIMT was measured by B-mode ultrasound scanning of right and left common carotid artery at baseline; week 24 of RCT [day 1 OLE]; and weeks 24, 48, and 80 of OLE. Descriptive analysis of cIMT was a prespecified HAUSER secondary endpoint, and inferential tests reported here were post-hoc.
151 patients had evaluable cIMT summary scores at ≥1 visit. From RCT baseline to week 24, mean cIMT increased by 0.006mm (SD=0.05) with placebo (n=37) and decreased by 0.003mm (SD=0.05) with evolocumab (n=76). From RCT baseline to OLE week 80, mean cIMT summary score decreased by 0.019mm (SD=0.04) and 0.012mm (SD=0.05), respectively, in patients who initially received placebo (n=34, P=0.007) versus receiving evolocumab throughout (n=59, P=0.067). Across patients who received evolocumab in OLE, mean cIMT significantly decreased by 0.011mm (SD=0.05) from OLE day 1 to week 80 (n=94, P=0.034).
In children with HeFH, evolocumab plus statin treatment up to 104 weeks led to regression in carotid arterial wall thickening.
杂合子家族性高胆固醇血症（HeFH）患儿的颈动脉内膜中层厚度（cIMT）更大。前蛋白转化酶枯草溶菌素/kexin 9型抑制剂单克隆抗体依洛尤单抗可大幅降低HeFH患儿的低密度脂蛋白胆固醇（LDL-C），并适度降低脂蛋白(a)。我们研究了依洛尤单抗对cIMT进展的影响。
HAUSER-RCT是一项随机、安慰剂对照试验。157例FH儿科患者（年龄10 - 17岁），尽管接受了他汀类药物治疗，但LDL-C>130mg/dL，每月接受420mg依洛尤单抗或安慰剂治疗24周。继续进入开放标签扩展期（HAUSER-OLE；n = 150）的患者接受80周的每月依洛尤单抗加他汀类药物治疗。在基线时；RCT的第24周[OLE第1天]；以及OLE的第24、48和80周，通过B型超声扫描左右颈总动脉测量cIMT。cIMT的描述性分析是预先设定的HAUSER次要终点，此处报告的推断性检验为事后检验。
151例患者在≥1次就诊时有可评估的cIMT汇总评分。从RCT基线到第
