Edoxaban, a once-daily oral anticoagulant, has been found to increase major bleeding in high-risk patients with atrial fibrillation (AF) who have had an intracranial hemorrhage, according to a recent study presented at the ESC Congress 2026. This finding challenges the conventional wisdom of using edoxaban in this patient population, which has been a topic of debate among medical professionals.
Atrial fibrillation is a common irregular heart rhythm and a leading cause of ischemic stroke, where a blood clot blocks blood flow to the brain. Oral anticoagulants like edoxaban are highly effective at preventing ischemic stroke in patients with AF, but they come with concerns over bleeding risk. These concerns are heightened in patients with AF who have had a prior intracranial hemorrhage, which includes bleeding within or around the brain.
The ENRICH-AF trial, a large-scale study conducted across 174 sites in 20 countries, aimed to evaluate the efficacy and safety of oral anticoagulants in these high-risk patients. The trial enrolled patients with high-risk AF and prior intracranial hemorrhage, but safety concerns led to the exclusion of patients with specific types of intracranial hemorrhage.
The study randomized participants to either edoxaban 60 mg once daily (with dose adjustments to 30 mg daily) or no anticoagulation. Over an average of 28 months of follow-up, edoxaban did not significantly reduce the primary endpoint of stroke (including ischemic and hemorrhagic stroke) or systemic embolism compared with no anticoagulation. In fact, the benefit of reduced ischemic stroke and myocardial infarction was offset by an almost three-fold excess in hemorrhagic stroke.
The primary safety outcome of major bleeding occurred in 11.6% of patients on edoxaban and 5.2% of patients on no anticoagulation, with a hazard ratio of 2.23. This finding highlights the increased risk of major bleeding associated with edoxaban in this patient population.
Professor Ashkan Shoamanesh, Principal Investigator of the ENRICH-AF trial, commented on the findings, stating that they do not support the use of edoxaban in unselected patients with AF after intracranial hemorrhage. He emphasized the need for an individualized decision-making approach, citing ongoing trials and a prospective meta-analysis that will provide more insights into stroke prevention in this vulnerable patient population.
This study raises important questions about the optimal management of stroke prevention in patients with AF and a history of intracranial hemorrhage. It highlights the complexity of clinical decision-making in this area and the need for further research to guide treatment choices.
