학술논문
Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk
Document Type
article
Author
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; Gaudet, Daniel
Source
European Heart Journal. 43(14)
Subject
Language
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