1. Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk
- Author
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Tardif, Jean-Claude, Investigators, for the Olezarsen Study, Karwatowska-Prokopczuk, Ewa, St Amour, Eric, Ballantyne, Christie M, Shapiro, Michael D, Moriarty, Patrick M, Baum, Seth J, Hurh, Eunju, Bartlett, Victoria J, Kingsbury, Joyce, Figueroa, Amparo L, Alexander, Veronica J, Tami, Joseph, Witztum, Joseph L, Geary, Richard S, St L O’Dea, Louis, Tsimikas, Sotirios, and Gaudet, Daniel
- Subjects
Clinical Trials and Supportive Activities ,Prevention ,Cardiovascular ,Heart Disease ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Apolipoprotein C-III ,Cardiovascular Diseases ,Cholesterol ,Heart Disease Risk Factors ,Humans ,Hypertriglyceridemia ,Lipoproteins ,Risk Factors ,Triglycerides ,Atherosclerosis ,Cardiovascular disease ,Cardiovascular risk factors ,Hypertriglyceridaemia ,apoC-III ,Antisense ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular System & Hematology - Abstract
AimsHypertriglyceridaemia 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 resultsA 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
- Published
- 2022