Rivaroxaban did not reduce the incidence of cognitive decline, stroke or transient ischemic attack (TIA) in patients younger than 65 with nonvalvular atrial fibrillation (AFib) and low risk for stroke, according to results from the BRAIN-AF trial presented at AHA 2024.

Researchers randomized a total of 1,235 patients (mean age 53 years and 25.6% women) across 53 centers in Canada to either rivaroxaban (15 mg daily) or placebo. For patients with vascular disease, a double dummy design was incorporated to ensure they received either rivaroxaban or aspirin. Cognitive testing was performed yearly and at the final visit. Researchers noted that AFib was paroxysmal, persistent, and permanent in 78.5%, 11.2%, and 10.4% of patients, respectively.

Overall results showed that during the follow-up period, the composite primary outcome of stroke, TIA or cognitive decline occurred in 130 patients (7.0% per year) randomized to rivaroxaban compared with 126 (6.4% per year) randomized to placebo. Researchers noted that cognitive decline accounted for 91% of the primary outcome; and 1 in 200 participants experienced major bleeding. Additionally, less than 1 in 100 (0.8%) per year of participants had a stroke.

The trial was terminated early, with the average follow-up reduced to 3.7 years vs. 5 years, based on a data safety and monitoring board recommendation finding it futile to continue given the clear lack of benefit from the study medication.

"Although numerous observational studies have reported an association between AFib and cognitive decline, we found that anticoagulation therapy initiated in relatively younger adults with AFib did not reduce this risk," said study lead author Lena Rivard, MD, MSc. "Patients should adhere to standard recommendations for cognitive health, including adopting a healthy lifestyle, engaging in activities that stimulate their brains and maintaining regular physical activity."