For years, doctors caring for patients with atrial fibrillation (AF) who have survived a brain bleed have faced one of medicine’s most difficult questions: how do you prevent stroke when the drugs that protect against it could trigger another bleed?
A large international randomized study in survivors of intracranial hemorrhage with atrial fibrillation has found that oral anticoagulants did not reduce stroke risk and significantly increased major bleeding, highlighting the urgent need for safer, more tailored treatment strategies in this vulnerable population.
PHRI senior scientist Ashkan Shoamanesh presented these results from ENRICH-AF at a Hot Line session at the European Society of Cardiology Congress 2026 on August 29.
Atrial fibrillation (AF) is the most common irregular heart rhythm and a major cause of ischemic stroke, the kind caused by a blood clot blocking blood flow to the brain. Oral anticoagulants are highly effective at reducing stroke risk in people with AF, but they also increase the risk of bleeding. That concern becomes especially serious in patients who have already experienced an intracranial hemorrhage, a bleed inside or around the brain.
Because these patients have been excluded from the large studies that established oral anticoagulants as a standard treatment, clinicians have been left without clear evidence to guide their decisions.
ENRICH-AF was conducted at 174 sites across 20 countries. It enrolled 948 patients with high-risk AF and a prior intracranial hemorrhage. Participants had a mean age of 77 years and 39 per cent were women.
Patients were randomly assigned to receive edoxaban, an oral anticoagulant taken once daily, or no anticoagulation. A safety review in 2023 led the trial’s independent monitoring board to recommend stopping enrollment of patients with certain types of brain bleeds (lobar intraparenchymal hemorrhage or convexity subarachnoid hemorrhage) due to unacceptably high rates of recurrent brain bleeding in those receiving edoxaban.
Over an average follow-up of 28 months, edoxaban did not significantly reduce the primary outcome of stroke or systemic embolism compared with no anticoagulation (11.8 per cent vs. 12.8 per cent).
While edoxaban reduced ischemic stroke and heart attack, that benefit was entirely offset by a nearly threefold increase in hemorrhagic stroke.
The risk of major bleeding was also significantly higher with edoxaban (11.6 per cent) than with no anticoagulation (5.2 per cent).
“Our findings do not support the use of edoxaban in unselected patients with AF after intracranial haemorrhage, but highlight the need for an individualised decision-making approach,” said Shoamanesh.
