Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk
| Autor: | Jean-Claude Tardif, Ewa Karwatowska-Prokopczuk, Eric St Amour, Christie M Ballantyne, Michael D Shapiro, Patrick M Moriarty, Seth J Baum, Eunju Hurh, Victoria J Bartlett, Joyce Kingsbury, Amparo L Figueroa, Veronica J Alexander, Joseph Tami, Joseph L Witztum, Richard S Geary, Louis St L O’Dea, Sotirios Tsimikas, Daniel Gaudet |
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| Rok vydání: | 2022 |
| Předmět: |
Lipoproteins
Clinical Trials and Supportive Activities Clinical Sciences Cardiorespiratory Medicine and Haematology Cardiovascular Risk Factors Clinical Research Hypertriglyceridaemia Humans Antisense Triglycerides Cardiovascular risk factors Hypertriglyceridemia Apolipoprotein C-III apoC-III Prevention Evaluation of treatments and therapeutic interventions Atherosclerosis Cardiovascular disease Cholesterol Heart Disease Good Health and Well Being Cardiovascular System & Hematology Cardiovascular Diseases Heart Disease Risk Factors 6.1 Pharmaceuticals Cardiology and Cardiovascular Medicine |
| Zdroj: | European heart journal, vol 43, iss 14 |
| Popis: | Aims Hypertriglyceridaemia is associated with increased risk of cardiovascular events. This clinical trial evaluated olezarsen, an N-acetyl-galactosamine-conjugated antisense oligonucleotide targeted to hepatic APOC3 mRNA to inhibit apolipoprotein C-III (apoC-III) production, in lowering triglyceride levels in patients at high risk for or with established cardiovascular disease. Methods and results A randomized, double-blind, placebo-controlled, dose-ranging study was conducted in 114 patients with fasting serum triglycerides 200–500 mg/dL (2.26–5.65 mmol/L). Patients received olezarsen (10 or 50 mg every 4 weeks, 15 mg every 2 weeks, or 10 mg every week) or saline placebo subcutaneously for 6–12 months. The primary endpoint was the percent change in fasting triglyceride levels from baseline to Month 6 of exposure. Baseline median (interquartile range) fasting triglyceride levels were 262 (222–329) mg/dL [2.96 (2.51–3.71) mmol/L]. Treatment with olezarsen resulted in mean percent triglyceride reductions of 23% with 10 mg every 4 weeks, 56% with 15 mg every 2 weeks, 60% with 10 mg every week, and 60% with 50 mg every 4 weeks, compared with increase by 6% for the pooled placebo group (P-values ranged from 0.0042 to Conclusion Olezarsen significantly reduced apoC-III, triglycerides, and atherogenic lipoproteins in patients with moderate hypertriglyceridaemia and at high risk for or with established cardiovascular disease. Trial registration number NCT03385239. |
| Databáze: | OpenAIRE |
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