Asundexian Shows Lower Stroke Risk in oral anticoagulant Naive Patients: JAMA
Researchers have found in a new study that oral anticoagulants OAC-naive patients experienced a smaller increase in stroke or systemic embolism with asundexian compared to apixaban. However, this effect was less pronounced in OAC-experienced patients. The underlying mechanism remains unclear and requires further research. The study published in JAMA Cardiology was conducted by John H.A. and fellow researchers.
The trial, a prespecified exploratory analysis of the OCEANIC-AF trial, examined whether the asundexian effect differed between OAC-naive and OAC-experienced patients. The trial enrolled 14,810 participants at 1035 sites in 38 countries, and data were analyzed in June-July 2024. Stroke or systemic embolism was the primary efficacy outcome, and the main safety outcome was major bleeding.
This analysis divided AF patients into two groups according to previous OAC exposure: OAC naive (≤6 weeks of previous OAC use) and OAC experienced (>6 weeks of previous OAC use). Patients were assigned randomly to asundexian, a new factor XIa inhibitor, or apixaban, an established anticoagulant. The study evaluated the rates of stroke or systemic embolism and major bleeding in the two groups to compare differences in anticoagulant efficacy and safety.
Key Findings
Out of 14,810 participants, 2493 (17%) were OAC naive (mean age: 72.6 years, 59% male), and 12,317 (83%) were OAC experienced (mean age: 74.2 years, 66% male).
Stroke or systemic embolism in the asundexian group occurred in 0.8% (10 of 1238) among OAC-naive patients versus 1.4% (88 of 6177) among OAC-experienced patients.
In the apixaban arm, stroke or systemic embolism happened in 0.6% (7 of 1255) of OAC-naive patients versus 0.3% (19 of 6140) in OAC-experienced patients.
OAC-naive patients had a lesser increase in stroke or systemic embolism with asundexian compared with apixaban (HR 1.42, 95% CI: 0.54-3.73) than OAC-experienced patients (HR 4.66, 95% CI: 2.84-7.65, p=0.03).
Major bleeding rates were reduced in OAC-naive (0.2%, 2 of 1228) and OAC-experienced (0.2%, 15 of 6145) patients receiving asundexian versus apixaban (1.0%, 13 of 1249 for OAC naive; 0.7%, 40 of 6115 for OAC experienced).
In the OCEANIC-AF trial, patients with nonexposure or limited prior OAC exposure had less increase in stroke or systemic embolism with asundexian than apixaban compared to patients with OAC exposure. The lower major bleeding risk with asundexian in both cohorts also underscores its potential as a safer anticoagulation therapy.
Reference:
Alexander JH, Lydon EJ, Piccini JP, et al. Asundexian or Apixaban in Patients With Atrial Fibrillation According to Prior Oral Anticoagulant Use: A Subgroup Analysis of the OCEANIC-AF Randomized Clinical Trial. JAMA Cardiol. Published online March 26, 2025. doi:10.1001/jamacardio.2025.0277
