Asundexian May Offer Safer Stroke Prevention in AF Patients New to Blood Thinners: OCEANIC-AF Analysis
USA: A recent subgroup analysis from the OCEANIC-AF randomized clinical trial highlights that asundexian, a novel oral Factor XIa inhibitor, may offer a favorable balance of safety and efficacy compared to apixaban in patients with atrial fibrillation (AF), especially those who were naive to oral anticoagulant (OAC) therapy.
"In these OAC-naive patients, asundexian was associated with a slight increase in stroke rates but demonstrated a lower risk of bleeding than apixaban, suggesting its potential as a safer alternative in select AF populations," the researchers reported in JAMA Cardiology.
In patients with atrial fibrillation, oral anticoagulants play a crucial role in reducing the risk of stroke. John H. Alexander, Duke University Medical Center, Durham, North Carolina, and colleagues aimed to explore whether the effectiveness and safety of a new OAC vary depending on a patient’s prior exposure to anticoagulant therapy.
For this purpose, the researchers conducted a subgroup analysis of the OCEANIC-AF trial, categorizing patients with atrial fibrillation as either OAC naive (≤6 weeks of prior use) or OAC experienced (>6 weeks). Asundexian, a novel Factor XIa inhibitor, was compared to apixaban across these groups. The trial involved participants from 1035 sites across 38 countries.
The key outcomes assessed were stroke or systemic embolism for efficacy and major bleeding for safety. Data were analyzed between June and July 2024 to understand how prior anticoagulant exposure influenced the response to asundexian versus Apixaban.
The following were the key findings of the study:
- Among 14,810 participants in the OCEANIC-AF trial, 17% were OAC naive, and 83% were OAC experienced. The mean age was 72.6 years for OAC-naive and 74.2 years for OAC-experienced participants.
- In the asundexian group, stroke or systemic embolism occurred in 0.8% of OAC-naive and 1.4% of OAC-experienced patients.
- In the apixaban group, stroke or systemic embolism rates were 0.6% in OAC-naive and 0.3% in OAC-experienced patients.
- The risk increase with asundexian versus apixaban was smaller in OAC-naive (HR 1.42) than in OAC-experienced patients (HR 4.66), with a significant interaction.
- Major bleeding was lower with asundexian in both OAC-naive (0.2%) and OAC-experienced (0.2%) patients, compared to apixaban (1.0% and 0.7%, respectively).
In the OCEANIC-AF trial, asundexian was associated with a smaller increase in stroke or systemic embolism and a comparable reduction in bleeding risk among OAC-naive patients compared to apixaban, with these differences less pronounced in OAC-experienced individuals.
"While the exact mechanism remains unclear, the findings highlight the need for further investigation into how prior anticoagulant exposure may influence treatment response," the authors wrote.
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
