What does this research mean for the field?

Factor XI/XIa inhibitors significantly reduce major and clinically relevant non-major bleeding compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation, but are associated with an increased risk of ischemic stroke. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The research aims to compare the effectiveness and safety of Factor XI inhibitors against direct oral anticoagulants in preventing thromboembolic events in atrial fibrillation patients.

February 27, 2026Open Access

Factor XI inhibitors versus direct oral anticoagulants for the prevention of thromboembolic events and safety in patients with atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials

Key Result

Factor XI inhibitors in atrial fibrillation reduce major bleeding but increase ischemic stroke risk compared to DOACs, with modestly lower all-cause mortality.

Key Points

The research aims to compare the effectiveness and safety of Factor XI inhibitors against direct oral anticoagulants in preventing thromboembolic events in atrial fibrillation patients.
Conducted a systematic review of randomized controlled trials
Compared outcomes related to thromboembolic events and bleeding
Evaluated mortality rates in both anticoagulant groups
Factor XI inhibitors reduced major and clinically relevant non-major bleeding compared to DOACs
Increased risk of ischemic stroke was observed with Factor XI inhibitors
A modest reduction in all-cause mortality was noted, raising efficacy concerns

Structured PICO

Do Factor XI/XIa inhibitors improve thromboembolic prevention and safety compared to DOACs in patients with atrial fibrillation?

Population

Patients with atrial fibrillation

Intervention

Factor XI/XIa inhibitors

Comparator

Direct oral anticoagulants (DOACs)

Outcome

Thromboembolic events (ischemic stroke) and safety (major and clinically relevant non-major bleeding)hard clinical

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.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

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.