Long-Term Efficacy and Safety of the Microsomal Triglyceride Transfer Protein Inhibitor Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
| Autor: | Dominique Larrey, Daniel J. Rader, Pamela Foulds, Claudia Stefanutti, Emma A. Meagher, LeAnne T. Bloedon, Daniel Gaudet, Dirk J. Blom, Maurizio Averna, Cesare R. Sirtori, Giovanni Battista Vigna, Robert A. Hegele, Marina Cuchel, Hendrik Du Toit Theron, Prediman K. Shah |
|---|---|
| Přispěvatelé: | Blom, D., Averna, M., Meagher, E., Toit Theron, H., Sirtori, C., Hegele, R., Shah, P., Gaudet, D., Stefanutti, C., Vigna, G., Larrey, D., Bloedon, L., Foulds, P., Rader, D., Cuchel, M. |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male medicine.medical_specialty Settore MED/09 - Medicina Interna Apolipoprotein B Socio-culturale Familial hypercholesterolemia 030204 cardiovascular system & hematology Gastroenterology Microsomal triglyceride transfer protein LDL Time Sudden cardiac death Hyperlipoproteinemia Type II 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) Internal medicine medicine Humans 030212 general & internal medicine Adverse effect lomitapide biology business.industry Cholesterol Anticholesteremic Agents Cholesterol LDL Benzimidazoles Carrier Proteins Female medicine.disease Lomitapide Endocrinology chemistry biology.protein lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine business Lipoprotein |
| Zdroj: | Circulation. 136:332-335 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circulationaha.117.028208 |
| Popis: | Homozygous familial hypercholesterolemia is a genetic disorder characterized by low-density lipoprotein (LDL)-receptor dysfunction, markedly elevated levels of LDL-cholesterol (LDL-C) and premature atherosclerosis. Patients are often poorly responsive to conventional lipid-lowering therapies that upregulate LDL-receptor expression.1 Lomitapide inhibits microsomal triglyceride transfer protein, which lipidates nascent apolipoprotein (apo)B-containing lipoproteins. In a pivotal 78-week open-label trial, lomitapide, titrated to the maximal tolerable dose, decreased LDL-C by 50% at the end of the efficacy phase (week 26) in patients with homozygous familial hypercholesterolemia.2 The principal adverse events included gastrointestinal disturbances, hepatic enzyme elevations, and increased liver fat. Here we provide additional long-term efficacy and safety data, including an exploratory analysis of the potential metabolic consequences of hepatic fat accumulation from an extension trial (NCT00943306). Patients continued on lomitapide at the maximally tolerated dose until transition to commercial or compassionate lomitapide. Lipid-lowering therapies, including apheresis, could be modified at the investigator’s discretion if LDL-C was |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|