Key Points:
- In patients with atrial fibrillation, it remains unclear if anticoagulation therapy reduces the incidence of neurocognitive impairment
- In this randomized clinical trial, young patients who had atrial fibrillation with low stroke risk were randomized to receiving either rivaroxaban 15mg or placebo.
- Anticoagulation with rivaroxaban 15mg in young patients with atrial fibrillation with low stroke risk did not reduce composite end point of ischemic stroke, TIA, and neurocognitive decline at a median of 3.7 years.
Emerging evidence suggests an association between atrial fibrillation (AF) and cognitive decline. However, it remains unknown whether oral anticoagulation reduces the incidence of cognitive decline in young patients with AF and low risk of stroke.
The Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF) trial was a multi-centered randomized clinical trial performed at 53 sites in Canada. The study randomized participants with atrial fibrillation without no CHADS-65 indication for anticoagulation (by Canadian Society Guidelines) to either rivaroxaban 15mg daily (611 participants) or placebo which also included aspirin in patients with vascular disease in a double-dummy design (624 participants). The primary outcome was composite stroke, TIA, or cognitive decline defined as reduction in MoCA score of greater than 2.
The results of the trial were presented as a late breaking clinical trial at the American Heart Association on November 16, 2024. Among the 1235 participants who underwent randomization, the average age was 53 years, and 25% were women. The study was terminated early after a mean follow-up of 3.7 years due to futility. A primary-outcome event occurred in 130 patients (7% per year) in the rivaroxaban arm versus 126 patients (6.4% per year) in the placebo arm (hazard ratio 1.10; 95% confidence interval [CI] 0.86 to 1.40, P = 0.46). Major bleeding occurred in 2 participants in the rivaroxaban arm versus 5 in the placebo arm (P = 0.27).
Limitations of the trial include cognitive decline was solely determined by the MoCA test. Rivaroxaban 15mg daily was used instead of the standard dose of 20mg was used to minimize bleeding risks. The trial was conducted in young patients with a low risk of stroke defined by the Canadian Guidelines such that results cannot be extrapolated to other populations. Finally, most of the patients in the trial were Caucasians.
At the late breaking presentation at the 2024 American Heart Association conference, Dr. Lena Rivard and colleagues concluded that “in patients with atrial fibrillation at low risk of stroke, anticoagulation with rivaroxaban 15mg daily does not reduce the incidence of cognitive decline, stroke, or TIA when compared to placebo.”