دورية أكاديمية
Evinacumab and Cardiovascular Outcome in Patients With Homozygous Familial Hypercholesterolemia.
| العنوان: | Evinacumab and Cardiovascular Outcome in Patients With Homozygous Familial Hypercholesterolemia. |
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| المؤلفون: | Béliard S; Aix Marseille University, APHM, INSERM, INRAE, C2VN, Marseille, France (S.B., R.V.).; APHM, Department of Nutrition, Metabolic Diseases, Endocrinology, La Conception Hospital, Marseille, France (S.B., R.V.)., Saheb S; Sorbonne Université, Lipidology and Cardiovascular Prevention Unit, Hémobiothérapie Unit, APHP, Hôpital Pitié-Salpètriêre, Paris (S.S.)., Litzler-Renault S; Université de Bourgogne, Pediatric Intensive Care and Monitoring Unit, CHU Dijon, France (S.L.-R.)., Vimont A; Department of Public Health Expertise, Paris, France (A.V.)., Valero R; Aix Marseille University, APHM, INSERM, INRAE, C2VN, Marseille, France (S.B., R.V.).; APHM, Department of Nutrition, Metabolic Diseases, Endocrinology, La Conception Hospital, Marseille, France (S.B., R.V.)., Bruckert É; Centre ELLA Santé, Paris, France (E.B.)., Farnier M; PEC2, EA 7460, Université de Bourgogne, Dijon, France (M.F.)., Gallo A; Sorbonne Université, INSERM UMR1166, Lipidology and Cardiovascular Prevention Unit, Department of Nutrition, APHP, Hôpital Pitié-Salpètriêre, Paris, France (A.G.). |
| المصدر: | Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2024 Jun; Vol. 44 (6), pp. 1447-1454. Date of Electronic Publication: 2024 May 02. |
| نوع المنشور: | Journal Article; Multicenter Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9505803 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4636 (Electronic) Linking ISSN: 10795642 NLM ISO Abbreviation: Arterioscler Thromb Vasc Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1998- : Baltimore, Md. : Lippincott Williams & Wilkins Original Publication: Dallas, TX : American Heart Association, c1995- |
| مواضيع طبية MeSH: | Hyperlipoproteinemia Type II*/blood , Hyperlipoproteinemia Type II*/drug therapy , Hyperlipoproteinemia Type II*/genetics , Hyperlipoproteinemia Type II*/complications , Hyperlipoproteinemia Type II*/diagnosis , Hyperlipoproteinemia Type II*/mortality , Cholesterol, LDL*/blood , Homozygote* , Angiopoietin-Like Protein 3* , Anticholesteremic Agents*/therapeutic use , Anticholesteremic Agents*/adverse effects, Humans ; Male ; Female ; Adult ; Middle Aged ; Blood Component Removal ; Biomarkers/blood ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal/adverse effects ; Time Factors ; Progression-Free Survival ; Young Adult ; Treatment Outcome ; Cardiovascular Diseases/prevention & control ; Cardiovascular Diseases/mortality ; Cardiovascular Diseases/epidemiology ; Adolescent |
| مستخلص: | Background: Patients with homozygous familial hypercholesterolemia (HoFH) remain at very high cardiovascular risk despite the best standard of care lipid-lowering treatment. The addition of evinacumab, an angiopoietin-like protein 3 monoclonal antibody, more than halves low-density lipoprotein cholesterol in short-term studies. This study evaluated whether the evinacumab response was durable in the long term and improved cardiovascular outcome. Methods: The OLE ELIPSE HoFH (Open-Label Extension to Evinacumab Lipid Studies in Patients With HoFH) study included newly diagnosed patients and those completing the ELIPSE HoFH trial, on stable lipid-lowering therapy including lipoprotein apheresis but not lomitapide. All patients received evinacumab (15 mg/kg intravenously) every 4 weeks, with no change in concomitant lipid-lowering treatment during the first 6 months. The primary efficacy end points were the mean absolute and percentage changes in low-density lipoprotein cholesterol from baseline to 6 months. A key secondary end point was cardiovascular event-free survival, which was compared with a control HoFH cohort not treated with evinacumab or lomitapide and matched for age, sex, and lipoprotein apheresis, derived from French Registry of Familial hypercholesterolemia. Results: Twelve patients, 5 women and 7 men (12-57 years), were enrolled in 3 centers in France. At 6 months, the mean low-density lipoprotein cholesterol reduction with evinacumab was 3.7 mmol/L or 56% (from 6.5 mmol/L at baseline to 2.8 mmol/L; P <0.0001) and was sustained over the median 3.5-year follow-up. No patients on evinacumab experienced cardiovascular events versus 13 events for 5/21 (24%) over 4 years in the control cohort (likelihood P =0.0267). Conclusions: Real-life, long-term evinacumab adjunctive to lipid-lowering therapy including lipoprotein apheresis led to sustained low-density lipoprotein cholesterol lowering and improved cardiovascular event-free survival of patients with HoFH. Competing Interests: Disclosures S. Béliard reports grants/honoraria from Ultragenyx for clinical trials and consultancy and from Amarin, Amgen, Amryt Novartis, Sanofi for clinical trials, conferences and consultancy. R. Valero reports personal or institutional honoraria for speakers’ bureaux, consultancy, clinical trials and travel/accommodation for professional purposes from Adelia Médical, Akcea, Amarin, Amgen, AstraZeneca, Boehringer-Ingelheim, Dinno Santé, Ionis, Janssen, Lilly, Merck and Co., Nestlé, Novartis, Novo Nordisk, Orkyn, Pfizer, Sanofi-Regeneron, Servier. E. Bruckert reports grants/honoraria for clinical trials/consultancy from MSD, Astra Zeneca, Genfit, Amgen, Sanofi-Aventis, Aegerion/Amryt, Lilly, Mylan/Viatris, Novartis, Pfizer, Servier, Organon, Akcea Therapeutics, and Ultragenyx. M. Farnier reports consultancy honoraria from Abbott, Amarin, Amgen, AstraZeneca, Austell, Kowa, Merck and Co., Organon, Pfizer, Recordati, Sanofi/Regeneron, Servier, SMB, Ultragenyx, and Viatris. A. Gallo reports research grants and honoraria from Amgen, Sanofi and Regeneron, Mylan Viatris, Merck and Co., Akcea Therapeutics, Amryt, Novartis, Servier, Ultragenyx, Amarin, and Eli Lilly. The other authors report no conflicts. |
| فهرسة مساهمة: | Keywords: cardiovascular diseases; homozygous familial hypercholesterolemia; myocardial infarction; risk factors; survival |
| المشرفين على المادة: | T8B2ORP1DW (evinacumab) 0 (Cholesterol, LDL) 0 (Angiopoietin-Like Protein 3) 0 (Anticholesteremic Agents) 0 (Biomarkers) 0 (Antibodies, Monoclonal) 0 (ANGPTL3 protein, human) |
| تواريخ الأحداث: | Date Created: 20240502 Date Completed: 20240522 Latest Revision: 20240710 |
| رمز التحديث: | 20240711 |
| DOI: | 10.1161/ATVBAHA.123.320609 |
| PMID: | 38695169 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1524-4636 |
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| DOI: | 10.1161/ATVBAHA.123.320609 |