Prescribing anticoagulation medications to adults younger than 65 years of age who have atrial fibrillation (AF) but no other risk factors for stroke does not reduce the risk of cognitive decline, stroke or transient ischaemic attack (TIA), according to late-breaking science presented recently at the 2024 American Heart Association (AHA) Scientific Sessions (16–18 November, Chicago, USA).
In Canada—where this trial, BRAIN-AF, was conducted—blood-thinning medications like rivaroxaban are prescribed to reduce the risk of stroke in people with AF who are 65 years old or older, or who have other stroke risk factors, including diabetes, heart failure, high blood pressure, or a prior stroke or TIA. However, as noted in an AHA press release, BRAIN-AF is the first large trial focused on assessing if anticoagulative medication can reduce the risk of cognitive decline, stroke or TIA among adults with AF but no other risk factors for stroke.
“Although numerous observational studies have reported an association between AF and cognitive decline, we found that anticoagulation therapy initiated in relatively younger adults with AF did not reduce this risk,” said study lead author Lena Rivard (Montreal Heart Institute, Montreal, Canada). “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.”
Participants were recruited to BRAIN-AF between April 2015 and November 2023, with the last follow-up exams being completed in May 2024. Although the trial was scheduled to allow for an average follow-up of five years, it was terminated early at an average follow-up of 3.7 years after the data safety and monitoring committee considered it futile to continue due to the clear lack of benefit from the study medication.
The trial included more than 1,235 adults (average age, 53 years; 26% women) being treated across 53 health centres in Canada who had AF but none of the standard risk factors that would necessitate the prescription of blood-thinning medication. Half of the study participants were randomly selected to receive 15mg of rivaroxaban daily, while the other half were randomly assigned to a placebo group. In addition, for the BRAIN-AF trial to include patients with vascular disease, a ‘double-dummy’ design was used. Participants were monitored yearly for cognitive decline (as per a reduction of two or more points on the Montreal cognitive assessment [MoCA] test), stroke or TIA. During the study’s follow-up period, if patients developed any of the standard indications for anticoagulation therapy, they were withdrawn from their study medication and switched to standard anticoagulation therapy.
After an average follow-up of almost four years, study analyses found that one in five participants experienced cognitive decline, stroke or TIA, with cognitive decline accounting for 91% of the primary outcome. Additionally, one in 200 had major bleeding. The participants also had a low incidence of stroke, at less than one in 100 (0.8%) per year.
Additionally, the researchers found that there were no differences in the outcomes of cognitive decline, stroke or TIA between those taking rivaroxaban and the placebo group. The rates of these conditions combined were 7% per year for those randomised to rivaroxaban versus 6.4% per year among those who received a placebo.
“In clinical practice, people younger than age 65 with AF tend to be overtreated with anticoagulant therapy, while older people who have indications for anticoagulation are under-treated,” Rivard commented. “Our study supports current guidelines by confirming that younger people with AF but no other risk factors for stroke have a low rate of stroke, and anticoagulation is not useful in reducing the risk of cognitive decline, as assessed by the Montreal cognitive assessment score.”
With more than 5,700 MoCA tests having been performed during the trial, the researchers are also analysing their results using biomarkers and genetic tests collected from most BRAIN-AF participants to better understand cognitive decline in patients with AF.
“The BRAIN-AF trial confirmed a high rate of cognitive decline during follow-up in younger adults. It is not known whether other interventions, such as ablation of AF, could have a positive impact on cognition in this population,” Rivard added.
Another point made by the researchers is that, to maximise safety, their trial used a low dose of rivaroxaban—and it remains unknown whether a higher dose of rivaroxaban or a different molecule would have been effective where the study medication was not.
