Compared with oral anticoagulant (OAC)-experienced patients, OAC-naïve patients received the same benefit in decreased bleeding risk with asundexian vs. apixaban but they were also less likely to experience the increased risk of stroke or systemic embolism with asundexian observed in OAC-experienced patients, according to a subgroup analysis of the OCEANIC-AF trial published March 26 in JAMA Cardiology.

The OCEANIC-AF trial randomized patients to either the novel factor XIa inhibitor asundexian 50 mg once daily or apixaban 5 mg or 2.5 mg twice daily. The trial was terminated early because asundexian was found to be less effective than apixaban.

In this prespecified subanalysis, 2,493 patients were categorized as OAC-naïve, with less than six weeks of prior OAC use, (mean age 72.6 years, 59% men; 76% White, 22% Asian) and 12,317 patients were OAC-experienced (mean age 74.2 years; 66.1% men; 69% White, 28% Asian). OAC-naïve patients tended to be younger, White, female and have fewer comorbidities. They also tended to have more first-diagnosed or paroxysmal atrial fibrillation (AFib) compared with the OAC-experienced group, who tended to have more long-standing persistent or permanent AFib.

Among OAC-experienced patients, the most common OACs used within 30 days before randomization were apixaban, rivaroxaban, edoxaban, vitamin K antagonists and dabigatran.

Results showed that the difference in bleeding rates, the main safety outcome, was similar between the two groups (0.2% vs. 1.0% in asundexian vs. apixaban for OAC-naïve; 0.2% vs. 0.7% for OAC-experienced).

However, OAC-naïve patients had a smaller difference in rates of stroke or systemic embolism, the primary endpoint, between asundexian and apixaban (hazard ratio [HR], 1.42) compared with OAC-experienced (HR, 4.66).

Among OAC-naïve patients, 0.8% experienced an event on asundexian vs. 0.6% on apixaban, while 1.4% vs. 0.3% OAC-experienced patients experienced events on the two medications, respectively. Among OAC-experienced patients, the increase in events with asundexian appeared within the first few weeks of treatment.

John H. Alexander, MD, MHS, et al., suggest that differences in demographics between OAC-naïve and OAC-experienced patients may have influenced outcomes. Also, they write that "there may be an effect of transitioning from a factor Xa to a factor XIa inhibitor, which inhibits coagulation further upstream and only via the intrinsic pathway. This effect could also potentially be exacerbated by a factor XIa inhibitor dose that provides incomplete factor XI inhibition."

Alexander, et al., write these findings are "clinically important differences" and that "these results suggest that patients with limited prior exposure to OACs may provide an important population for the evaluation of factor XI/XIa inhibitors as a new class of anticoagulants."