TY - JOUR
T1 - Asundexian versus Apixaban in Patients with Atrial Fibrillation
AU - Piccini, Jonathan P.
AU - Patel, Manesh R.
AU - Steffel, Jan
AU - Ferdinand, Keith
AU - Van Gelder, Isabelle C.
AU - Russo, Andrea M.
AU - Ma, Chang-Sheng
AU - Goodman, Shaun G.
AU - Oldgren, Jonas
AU - Hammett, Christopher
AU - Lopes, Renato D.
AU - Akao, Masaharu
AU - De Caterina, Raffaele
AU - Kirchhof, Paulus
AU - Gorog, Diana A.
AU - Hemels, Martin
AU - Rienstra, Michiel
AU - Jones, W. Schuyler
AU - Harrington, Josephine
AU - Lip, Gregory Y. H.
AU - Ellis, Stephen J.
AU - Rockhold, Frank W.
AU - Neumann, Christoph
AU - Alexander, John H.
AU - Viethen, Thomas
AU - Hung, James
AU - Coppolecchia, Rosa
AU - Mundl, Hardi
AU - Caso, Valeria
AU - OCEANIC-AF Steering Committee and Investigators
A2 - Joensen, Albert Marni
A2 - Delekta, Joanna
A2 - Riahi, Sam
N1 - Copyright © 2024 Massachusetts Medical Society.
PY - 2025/1/2
Y1 - 2025/1/2
N2 - 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.).
AB - 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.).
KW - Administration, Oral
KW - Aged
KW - Aged, 80 and over
KW - Anticoagulants/administration & dosage
KW - Atrial Fibrillation/drug therapy
KW - Benzamides/administration & dosage
KW - Double-Blind Method
KW - Embolism/epidemiology
KW - Factor Xa Inhibitors/administration & dosage
KW - Female
KW - Hemorrhage/chemically induced
KW - Humans
KW - Hydrocarbons, Fluorinated
KW - Intention to Treat Analysis
KW - Male
KW - Pyrazoles/administration & dosage
KW - Pyridones/administration & dosage
KW - Stroke/epidemiology
KW - Triazoles/administration & dosage
U2 - 10.1056/NEJMoa2407105
DO - 10.1056/NEJMoa2407105
M3 - Journal article
C2 - 39225267
SN - 0028-4793
VL - 392
SP - 23
EP - 32
JO - The New England Journal of Medicine
JF - The New England Journal of Medicine
IS - 1
ER -