{"id":"b4fd706e286a","type":"article","url":"https://hartvaat.nl/2023/11/01/evinacumab-bij-refractaire-hypercholesterolemie-langetermijn-effectiviteit-en-ve/","title":"Evinacumab bij refractaire hypercholesterolemie: langetermijn effectiviteit en veiligheid","title_en":"Longer-Term Efficacy and Safety of Evinacumab in Patients With Refractory Hypercholesterolemia.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["abelacimab","bempedoïnezuur","cetp-remmers","dyslipidemie","ezetimibe","familiaire-hypercholesterolemie-screening","ldl-cholesterol","lipidenverlaging","niet-statine-therapie","pcsk9-remmers","pelacarsen","statines","yellow-iii"],"journal":"JAMA cardiology","doi":"10.1001/jamacardio.2023.2921","source_url":"https://doi.org/10.1001/jamacardio.2023.2921","authors":["Robert S Rosenson","Lesley J Burgess","Christoph F Ebenbichler","Seth J Baum","Erik S G Stroes","Shazia Ali","Nagwa Khilla","Jennifer McGinniss","Daniel Gaudet","Robert Pordy"],"significance":7,"published":"2023-11-01","source_date":"2023-11-01","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/lpa-meten-wanneer-waarom/"],"congress":"","summary_en":"Longer-term data on evinacumab confirmed sustained LDL cholesterol reduction in patients with refractory hypercholesterolemia, providing reassurance about the durability and safety of ANGPTL3 inhibition over extended treatment periods.","created":"2026-07-03T10:30:40Z","updated":"2026-07-03T13:29:43Z","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":"Langetermijndata van evinacumab, een ANGPTL3-antilichaam, bevestigden duurzame LDL-verlaging bij patiënten met refractaire hypercholesterolemie die onvoldoende reageren op maximale standaardtherapie. Het middel biedt een uitweg voor de moeilijkst te behandelen groep.","abstract_original":"IMPORTANCE: Patients with refractory hypercholesterolemia who do not achieve their guideline-defined low-density lipoprotein cholesterol (LDL-C) thresholds despite treatment with maximally tolerated combinations of lipid-lowering therapies (LLTs) have an increased risk of atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE: To evaluate longer-term efficacy and safety of evinacumab in patients with refractory hypercholesterolemia. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial included a 2-week screening period followed by a 16-week double-blind treatment period (DBTP) for subcutaneous regimens (evinacumab, 450 mg, once weekly [QW]; evinacumab, 300 mg, QW; evinacumab, 300 mg, every 2 weeks; or placebo QW) or a 24-week DBTP for intravenous regimens (evinacumab, 15 mg/kg, every 4 weeks [Q4W]; evinacumab, 5 mg/kg, Q4W; or placebo Q4W); a 48-week open-label treatment period (OLTP) for intravenous treatment only; and a 24-week follow-up period. Patients from 85 sites across 20 countries were recruited for the study; patients with primary hypercholesterolemia (defined as heterozygous familial hypercholesterolemia or established clinical ASCVD without familial hypercholesterolemia) who entered the 48-week OLTP were included. In addition, the patients' hypercholesterolemia was refractory to maximally tolerated LLTs. INTERVENTIONS: All patients entering the OLTP received evinacumab, 15 mg/kg, intravenously Q4W. MAIN OUTCOMES AND MEASURES: Efficacy outcomes included change in LDL-C level and other lipid/lipoprotein parameters from baseline to week 72 (end of the OLTP). Safety outcomes included assessment of treatment-emergent adverse events (TEAEs). RESULTS: A total of 96 patients (mean [SD] age, 54.4 [11.3] years; 52 female [54.2%]) entered the OLTP, of whom 88 (91.7%) completed the OLTP. Mean (SD) baseline LDL-C level was 145.9 (55.2) mg/dL. At week 72, evinacumab, 15 mg/kg, reduced mean (SD) LDL-C level from baseline by 45.5% (28.7%) in the overall cohort. Evinacumab, 15 mg/kg, reduced mean (SD) apolipoprotein B (38.0% [22.1%]), non-high density lipoprotein cholesterol (48.4% [23.2%]), total cholesterol (42.6% [17.5%]), and median (IQR) fasting triglyceride (57.2% [65.4%-44.4%]) levels at week 72 from baseline in the overall cohort. TEAEs occurred in 78 of 96 patients (81.3%). Serious TEAEs occurred in 9 of 96 patients (9.4%); all were considered unrelated to study treatment. CONCLUSIONS AND RELEVANCE: In patients with refractory hypercholesterolemia, evinacumab provided sustained reductions in LDL-C level and was generally well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03175367."}