Effect of Vupanorsen on Non–High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70

Medientyp: E-Artikel
Titel: Effect of Vupanorsen on Non–High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70
Beteiligte: Bergmark, Brian A.; Marston, Nicholas A.; Bramson, Candace R.; Curto, Madelyn; Ramos, Vesper; Jevne, Alexandra; Kuder, Julia F.; Park, Jeong-Gun; Murphy, Sabina A.; Verma, Subodh; Wojakowski, Wojtek; Terra, Steven G.; Sabatine, Marc S.; Wiviott, Stephen D.; Carbonneau, Diane; Poulin-Robitaille, Raphael; Wayne, Jeffrey; Lee, Keung; Mujica Trenche, Samuel; Dzongowski, Petros; Gaudet, Daniel; Van, Joanna; Ajani, Dilawar; Bays, Harold; [...]
Erschienen: Ovid Technologies (Wolters Kluwer Health), 2022
Erschienen in: Circulation
Sprache: Englisch
DOI: 10.1161/circulationaha.122.059266
ISSN: 1524-4539; 0009-7322
Schlagwörter: Physiology (medical) ; Cardiology and Cardiovascular Medicine
Entstehung:
Anmerkungen:
Beschreibung: <jats:sec> <jats:title>Background:</jats:title> <jats:p> Genetic loss-of-function variants in <jats:italic>ANGPTL3</jats:italic> are associated with lower levels of plasma lipids. Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis. </jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>Adults with non–high-density lipoprotein cholesterol (non-HDL-C) ≥100 mg/dL and triglycerides 150 to 500 mg/dL on statin therapy were randomized in a double-blind fashion to placebo or 1 of 7 vupanorsen dose regimens (80, 120, or 160 mg SC every 4 weeks, or 60, 80, 120, or 160 mg SC every 2 weeks). The primary end point was placebo-adjusted percentage change from baseline in non–HDL-C at 24 weeks. Secondary end points included placebo-adjusted percentage changes from baseline in triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and ANGPTL3.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> Two hundred eighty-six subjects were randomized: 44 to placebo and 242 to vupanorsen. The median age was 64 (interquartile range, 58–69) years, 44% were female, the median non–HDL-C was 132.4 (interquartile range, 118.0–154.1) mg/dL, and the median triglycerides were 216.2 (interquartile range, 181.4–270.4) mg/dL. Vupanorsen resulted in significant decreases from baseline over placebo in non–HDL-C ranging from 22.0% in the 60 mg every 2 weeks arm to 27.7% in the 80 mg every 2 weeks arm (all <jats:italic>P</jats:italic> <0.001 for all doses). There were dose-dependent reductions in triglycerides that ranged from 41.3% to 56.8% (all <jats:italic>P</jats:italic> <0.001). The effects on LDL-C and ApoB were more modest (7.9%–16.0% and 6.0%–15.1%, respectively) and without a clear dose-response relationship‚ and only the higher reductions achieved statistical significance. ANGPTL3 levels were decreased in a dose-dependent manner by 69.9% to 95.2% (all <jats:italic>P</jats:italic> <0.001). There were no confirmed instances of significant decline in renal function or platelet count with vupanorsen. Injection site reactions and >3× elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively), and there was a dose-dependent increase in hepatic fat fraction (up to 76%). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Vupanorsen administered at monthly equivalent doses from 80 to 320 mg significantly reduced non–HDL-C and additional lipid parameters. Injection site reactions and liver enzyme elevations were more frequent at higher doses, and there was a dose-dependent increase in hepatic fat fraction.</jats:p> </jats:sec> <jats:sec> <jats:title>Registration:</jats:title> <jats:p> URL: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov">https://clinicaltrials.gov</jats:ext-link> ; Unique identifier: NCT04516291. </jats:p> </jats:sec>
Zugangsstatus: Freier Zugang

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: