Factor XI inhibitors in atrial fibrillation reduce major bleeding but increase ischemic stroke risk compared to DOACs, with modestly lower all-cause mortality.
Do Factor XI/XIa inhibitors improve thromboembolic prevention and safety compared to DOACs in patients with atrial fibrillation?
While Factor XI/XIa inhibitors reduce bleeding compared to DOACs in atrial fibrillation, their increased risk of ischemic stroke raises concerns about their net clinical benefit.
In patients with atrial fibrillation, Factor XI/XIa inhibitors significantly reduce major and clinically relevant non-major bleeding compared to DOACs but are associated with an increased risk of ischemic stroke. While a modest reduction in all-cause mortality was noted, the unfavorable efficacy profile for stroke prevention raises concerns about the net clinical benefit of the currently evaluated FXI/XIa inhibitors in this population. Further data from ongoing large-scale trials are needed to define their ultimate clinical role.
Alcântara et al. (2026) studied this question. Factor XI inhibitors in atrial fibrillation reduce major bleeding but increase ischemic stroke risk compared to DOACs, with modestly lower all-cause mortality.