Evolocumab treatment reduces carotid intima-media thickness in paediatric patients with heterozygous familial hypercholesterolaemia

Abstract Aims 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 LDL cholesterol (LDL-C) in children with HeFH. We investigated evolocumab’s effect on cIMT progression. Methods and results HAUSER-RCT was a randomized, placebo-controlled trial. One hundred fifty-seven paediatric patients with FH (age: 10–17 years) and LDL-C > 130 mg/dL despite statin therapy received monthly evolocumab 420 mg or placebo for 24 weeks. Patients who continued into an open-label extension (OLE) (HAUSER-OLE; n = 150) received 80 weeks of monthly evolocumab plus statins. Carotid intima-media thickness was measured by B-mode ultrasound scanning of right and left common carotid artery at baseline; Week 24 of randomized controlled trial (RCT) (Day 1 OLE); and Weeks 24, 48, and 80 of OLE. Descriptive analysis of cIMT was a pre-specified HAUSER secondary endpoint, and inferential tests reported here were post hoc. One hundred fifty-one patients had evaluable cIMT summary scores at ≥ 1 visit. From RCT baseline to Week 24, mean cIMT increased by 0.006 mm (SD = 0.05) with placebo (n = 37) and decreased by 0.003 mm (SD = 0.05) with evolocumab (n = 76). From RCT baseline to OLE Week 80, mean cIMT summary score decreased by 0.019 mm (SD = 0.04) and 0.012 mm (SD = 0.05), respectively, in patients who initially received placebo (n = 34, P = 0.007) vs. receiving evolocumab throughout (n = 59, P = 0.067). Across patients who received evolocumab in OLE, mean cIMT significantly decreased by 0.011 mm (SD = 0.05) from OLE Day 1 to Week 80 (n = 94, P = 0.034). Conclusion In children with HeFH, evolocumab plus statin treatment up to 104 weeks led to regression in carotid arterial wall thickening. Registration ClinicalTrials.gov: NCT02624869