Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations
| Autor: | Min-Ji Charng, Evan A. Stein, Flemming Skovby, Daniel Gaudet, Mafauzy Mohamed, Etienne Sokal, Mattias Sundén, Joel S. Raichlen, Frederick J. Raal, Stefan Carlsson, John J.P. Kastelein, Albert Wiegman, Ilse K. Luirink, Eldad J. Dann |
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| Přispěvatelé: | Paediatric Metabolic Diseases, APH - Methodology, APH - Quality of Care, Graduate School, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, ACS - Atherosclerosis & ischemic syndromes, ACS - Pulmonary hypertension & thrombosis |
| Rok vydání: | 2017 |
| Předmět: |
Male
medicine.medical_specialty Statin Adolescent medicine.drug_class DNA Mutational Analysis Familial hypercholesterolemia 030204 cardiovascular system & hematology Placebo Hyperlipoproteinemia Type II 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Double-Blind Method Ezetimibe Internal medicine medicine Humans Rosuvastatin 030212 general & internal medicine Rosuvastatin Calcium Child Adverse effect Cross-Over Studies Dose-Response Relationship Drug business.industry Cholesterol Anticholesteremic Agents Homozygote nutritional and metabolic diseases Cholesterol LDL DNA medicine.disease Crossover study Treatment Outcome Endocrinology chemistry Mutation Female lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine business Follow-Up Studies medicine.drug |
| Zdroj: | Journal of the American College of Cardiology, 70(9), 1162-1170. Elsevier USA |
| ISSN: | 0735-1097 |
| Popis: | BACKGROUND Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been formally evaluated in, or approved for, HoFH children. OBJECTIVES The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations. METHODS This was a randomized, double-blind, 12-week, crossover study of rosuvastatin 20 mg versus placebo, followed by 12 weeks of open-label rosuvastatin. Patients discontinued all lipid-lowering treatment except ezetimibe and/or apheresis. Clinical and laboratory assessments were performed every 6 weeks. The relationship between LDL-C response and genetic mutations was assessed by adding children and adults from a prior HoFH rosuvastatin trial. RESULTS Twenty patients were screened, 14 randomized, and 13 completed the study. The mean age was 10.9 years; 8 patients were on ezetimibe and 7 on apheresis. Mean LDL-C was 481 mg/dl (range: 229 to 742 mg/dl) on placebo and 396 mg/dl (range: 130 to 700 mg/dl) on rosuvastatin, producing a mean 85.4 mg/dl (22.3%) difference (p = 0.005). Efficacy was similar regardless of age or use of ezetimibe or apheresis, and was maintained for 12 weeks. Adverse events were few and not serious. Patients with 2 defective versus 2 negative LDL receptor mutations had mean LDL-C reductions of 23.5% (p = 0.0044) and 14% (p = 0.038), respectively. CONCLUSIONS This first-ever pediatric HoFH statin trial demonstrated safe and effective LDL-C reduction with rosuvastatin 20 mg alone or added to ezetimibe and/or apheresis. The LDL-C response in children and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198) (C) 2017 by the American College of Cardiology Foundation |
| Databáze: | OpenAIRE |
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