{"id":"3fd8f9a92a38","type":"article","url":"https://hartvaat.nl/2020/08/20/evinacumab-bij-homozygoot-familiaire-hypercholesterolemie-nejm/","title":"Evinacumab bij homozygoot familiaire hypercholesterolemie: NEJM","title_en":"Evinacumab for Homozygous Familial Hypercholesterolemia.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["cardiovasculaire-genetica","ezetimibe","familiaire-hypercholesterolemie","familiaire-hypercholesterolemie-screening","yellow-iii"],"journal":"The New England journal of medicine","doi":"10.1056/NEJMoa2004215","source_url":"https://doi.org/10.1056/NEJMoa2004215","authors":["Frederick J Raal","Robert S Rosenson","Laurens F Reeskamp","G Kees Hovingh","John J P Kastelein","Paolo Rubba","Shazia Ali","Poulabi Banerjee","Kuo-Chen Chan","Daniel A Gipe","Nagwa Khilla","Robert Pordy","David M Weinreich","George D Yancopoulos","Yi Zhang","Daniel Gaudet"],"significance":10,"published":"2020-08-20","source_date":"2020-08-20","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/familiaire-hypercholesterolemie/","https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/"],"congress":"","summary_en":"This pivotal trial showed that evinacumab, an ANGPTL3 inhibitor, reduced LDL cholesterol by 47% in patients with homozygous familial hypercholesterolemia, a condition where conventional therapies including PCSK9 inhibitors are often ineffective due to absent LDL receptors. Evinacumab represents the first LDL-receptor-independent approach to cholesterol lowering.","created":"2026-07-03T10:28:43Z","updated":"2026-07-03T13:27:53Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"NEJM trial van evinacumab (ANGPTL3-remmer) bij homozygote FH. Eerste behandeling die LDL-verlaging biedt onafhankelijk van de LDL-receptor. Doorbraak voor de zwaarste FH.","abstract_original":"BACKGROUND: Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null-null) or impaired (non-null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24. RESULTS: The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of -49.0 percentage points (95% confidence interval [CI], -65.0 to -33.1; P<0.001); the between-group least-squares mean absolute difference in the LDL cholesterol level was -132.1 mg per deciliter (95% CI, -175.3 to -88.9; P<0.001). The LDL cholesterol level was lower in the evinacumab group than in the placebo group in patients with null-null variants (-43.4% vs. +16.2%) and in those with non-null variants (-49.1% vs. -3.8%). Adverse events were similar in the two groups. CONCLUSIONS: In patients with homozygous familial hypercholesterolemia receiving maximum doses of lipid-lowering therapy, the reduction from baseline in the LDL cholesterol level in the evinacumab group, as compared with the small increase in the placebo group, resulted in a between-group difference of 49.0 percentage points at 24 weeks. (Funded by Regeneron Pharmaceuticals; ELIPSE HoFH ClinicalTrials.gov number, NCT03399786.)."}