Asundexian versus Apixaban in Patients with Atrial Fibrillation

Jonathan P. Piccini*, Manesh R. Patel, Jan Steffel, Keith Ferdinand, Isabelle C. Van Gelder, Andrea M. Russo, Chang-Sheng Ma, Shaun G. Goodman, Jonas Oldgren, Christopher Hammett, Renato D. Lopes, Masaharu Akao, Raffaele De Caterina, Paulus Kirchhof, Diana A. Gorog, Martin Hemels, Michiel Rienstra, W. Schuyler Jones, Josephine Harrington, Gregory Y. H. LipStephen J. Ellis, Frank W. Rockhold, Christoph Neumann, John H. Alexander, Thomas Viethen, James Hung, Rosa Coppolecchia, Hardi Mundl, Valeria Caso, OCEANIC-AF Steering Committee and Investigators, Albert Marni Joensen (Member of study group), Joanna Delekta (Member of study group), Sam Riahi (Member of study group)

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

18 Citations (Scopus)

Abstract

BACKGROUND: Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding.

METHODS: In a phase 3, international, double-blind trial, we randomly assigned high-risk patients with atrial fibrillation in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban. The primary efficacy objective was to determine whether asundexian is at least noninferior to apixaban for the prevention of stroke or systemic embolism. The primary safety objective was to determine whether asundexian is superior to apixaban with respect to major bleeding events.

RESULTS: A total of 14,810 randomly assigned patients were included in the intention-to-treat population. The mean (±SD) age of the patients was 73.9±7.7 years, 35.2% were women, 18.6% had chronic kidney disease, 18.2% had a previous stroke or transient ischemic attack, 16.8% had received oral anticoagulants for no more than 6 weeks, and the mean CHA2DS2-VASc score (range, 0 to 9, with higher scores indicating a greater risk of stroke) was 4.3±1.3. The trial was stopped prematurely at the recommendation of the independent data monitoring committee. Stroke or systemic embolism occurred in 98 patients (1.3%) assigned to receive asundexian and in 26 (0.4%) assigned to receive apixaban (hazard ratio, 3.79; 95% confidence interval [CI], 2.46 to 5.83). Major bleeding occurred in 17 patients (0.2%) who received asundexian and in 53 (0.7%) who received apixaban (hazard ratio, 0.32; 95% CI, 0.18 to 0.55). The incidence of any adverse event appeared to be similar in the two groups.

CONCLUSIONS: Among patients with atrial fibrillation at risk for stroke, treatment with asundexian at a dose of 50 mg once daily was associated with a higher incidence of stroke or systemic embolism than treatment with apixaban in the period before the trial was stopped prematurely. There were fewer major bleeding events with asundexian than with apixaban during this time. (Funded by Bayer; OCEANIC-AF ClinicalTrials.gov number, NCT05643573; EudraCT number, 2022-000758-28.).

Original languageEnglish
JournalThe New England Journal of Medicine
Volume392
Issue number1
Pages (from-to)23-32
Number of pages10
ISSN0028-4793
DOIs
Publication statusPublished - 2 Jan 2025

Bibliographical note

Copyright © 2024 Massachusetts Medical Society.

Keywords

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticoagulants/administration & dosage
  • Atrial Fibrillation/drug therapy
  • Benzamides/administration & dosage
  • Double-Blind Method
  • Embolism/epidemiology
  • Factor Xa Inhibitors/administration & dosage
  • Female
  • Hemorrhage/chemically induced
  • Humans
  • Hydrocarbons, Fluorinated
  • Intention to Treat Analysis
  • Male
  • Pyrazoles/administration & dosage
  • Pyridones/administration & dosage
  • Stroke/epidemiology
  • Triazoles/administration & dosage

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