Arrhythmias & electrophysiologyRandomised controlled trial
Anticoagulation to prevent ischemic stroke and neurocognitive impairment in atrial fibrillation: the BRAIN-AF randomized clinical trial
- Randomised controlled trial
- multicentre
- double-blind
- placebo-controlled
- planned interim analysis
- stopped early for futility
- Trial halted after meeting predetermined futility criterion following planned interim analysis
Authors' conclusion
In conclusion, despite the high incidence of cognitive decline observed among patients with AF and low stroke risk, the BRAIN-AF trial, which tested a low dose of rivaroxaban to prevent stroke, transient ischemic attack and cognitive decline in patients with prior AF, was stopped early due to futility.
Study context
- Population
- Patients with atrial fibrillation (AF) and low thromboembolic risk (CHA2DS2-VASc 0 or 1, excluding female sex)of intended 1,424
- Participants
- 1,235 patients
- Comparison
- Rivaroxaban 15 mg daily vs placebo
- Primary endpoint
- Composite of:
- Cognitive decline (≥2-point drop in Montreal Cognitive Assessment)
- Stroke or TIA with motor deficit or aphasia
- Follow-up
- Median 3.7 years
Primary result
As reported in the abstract
Hazard ratio
1.10
95% CI 0.86–1.40
P = 0.46
By group
Rivaroxaban vs Placebo
HR 1.10 (95% CI 0.86–1.40); P = 0.46
- Primary outcome occurred overall
- 256 (20.7%)
- Conditional power: probability of significant effect if continued to 410 events
- 1.2%
Safety
per year
| Outcome | Rivaroxaban | Placebo |
|---|---|---|
| Major bleeding | 0.09% | 0.21% |
Original publication
Anticoagulation to prevent ischemic stroke and neurocognitive impairment in atrial fibrillation: the BRAIN-AF randomized clinical trial. Nat Med. Published 7 January 2026. doi:10.1038/s41591-025-04101-y
Summarised from the published abstract; every number is checked against it