Aim: 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.
Methods: 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.
Results: 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).
Conclusions: In children with HeFH, evolocumab plus statin treatment up to 104 weeks led to regression in carotid arterial wall thickening.
Keywords: Evolocumab; PCSK9 inhibitor; atherosclerotic cardiovascular disease; carotid intima-media thickness; paediatric.
Children with a genetic disorder that causes high cholesterol in the blood from birth onwards develop heart disease in early adulthood. In these children, thickening of the carotid artery wall is often observed and is an early warning sign of disease in the arteries. Children with high cholesterol despite taking a maximum dose of statins, can be treated with evolocumab, a medication that lowers blood cholesterol. In this study, we tested whether treating children with evolocumab had an effect on the thickening of the carotid artery wall in children with high cholesterol. One third of the children on statins received placebo for 24 weeks followed by evolocumab for 80 weeks (placebo/evolocumab), two thirds received evolocumab for 24 weeks followed by evolocumab for 80 weeks (evolocumab/evolocumab). Thickening of the carotid artery wall increased in patients who received placebo during the 24-week period, while it decreased in patients who received evolocumab. Thickening of the carotid artery wall decreased in the evolocumab/evolocumab group as well as in the placebo/evolocumab group during the 80-week period when all patients received evolocumab. Our results demonstrate that treatment with evolocumab prevented thickening of the carotid artery wall in children with high cholesterol on maximum tolerated statins. These results suggest that evolocumab reduces the risk of disease in the arteries of young people.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.