In children with HeFH, evolocumab decreased mean cIMT by 0.003 mm at 24 weeks compared to a 0.006 mm increase with placebo, with continued regression up to 104 weeks.
RCT (n=157)
placebo-controlled
randomized
Does evolocumab reduce carotid intima-media thickness in pediatric patients with heterozygous familial hypercholesterolaemia on statin therapy?
Evolocumab added to statin therapy promotes regression of carotid intima-media thickness in pediatric patients with heterozygous familial hypercholesterolemia.
Absolute Event Rate: -0.003% vs 0.006%
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
Wiegman et al. (Tue,) conducted a rct in heterozygous familial hypercholesterolaemia (HeFH) (n=157). evolocumab vs. placebo was evaluated on change in mean cIMT from RCT baseline to Week 24. In children with HeFH, evolocumab decreased mean cIMT by 0.003 mm at 24 weeks compared to a 0.006 mm increase with placebo, with continued regression up to 104 weeks.