Initiating oral anticoagulation with rivaroxaban in younger adults diagnosed with atrial fibrillation (AF) does not reduce the risk of neurocognitive decline, stroke, or transient ischemic attack (TIA), according to results from the BRAIN-AF trial presented at the American Heart Association 2024 Scientific Sessions.
The study casts doubt on the strategy of using oral anticoagulants (OAC) in AF patients under 65 without other cardiovascular risk factors, a practice modeled after its use in older AF patients to prevent future complications. Léna Rivard, MD, highlighted that the trial does not support using rivaroxaban, even at a lower dose to mitigate bleeding risk, in younger, lower-risk patients.
BRAIN-AF Trial Details
The BRAIN-AF trial was prematurely halted due to futility after a data safety and monitoring committee review. The final analysis included 1,235 patients followed for a mean of 3.7 years. The primary endpoint, cognitive decline (defined as a decrease of 2 or more points on the Montreal Cognitive Assessment [MoCA]), stroke, or TIA, did not significantly differ between the rivaroxaban and placebo groups (HR 1.10; 95% CI 0.86-1.40).
Secondary outcomes, including bleeding events, and subgroup analyses also showed no benefit from anticoagulation. The study population consisted of individuals with no prior stroke or TIA, hypertension, diabetes, congestive heart failure, or other indications for oral anticoagulants. Rivard noted that the observed cognitive decline, with 18% of the population decreasing by two points on the MoCA, was striking and concerning.
Expert Perspectives on Cognitive Decline
Experts discussing BRAIN-AF emphasized the unexpected cognitive decline observed in the study. Andrea Russo, MD, noted that the trial provides a better understanding of potential mechanisms impacting cognitive decline in AF patients and should encourage future studies to include cognitive decline or dementia as key endpoints.
Sana Al-Khatib, MD, highlighted the growing recognition of cognitive decline in AF patients and the need to understand its mechanisms and find ways to lower the risk. She suggested that further analysis of the BRAIN-AF data might provide insights, particularly given the relatively healthy, low-risk profile of the study population.
Future Research Directions
BRAIN-AF investigators are continuing to analyze their data, including MRI, biomarker, and genetic data, to identify predictors of cognitive decline. Rivard suggested that future studies should explore whether different medications or AF ablation can reduce long-term cognitive dysfunction in similar patients. Neurologist Hooman Kamel, MD, emphasized the complex relationship between atrial pathology, AF, and neurological pathology, suggesting that brain infarcts may not be the primary mechanism of cognitive impairment in AF.
Kamel concluded that the trial clarifies that expanding anticoagulation to younger, healthier individuals to improve brain health is not currently warranted. He advocated for including broader measures of brain health in future studies of new and emerging AF therapies.
