Prescribing anticoagulation medications to adults under age 65 with atrial fibrillation (AFib) but no other risk factors for stroke did not reduce the risk of cognitive decline, stroke or TIA, according to newly presented science today at the American Heart’s Scientific Sessions 2024 Association. The meeting, November 16-18, 2024, in Chicago, is a premier global exchange of the latest scientific advances, research and evidence-based clinical practice updates in cardiovascular science.
In Canada, anticoagulation medications such as rivaroxaban are prescribed to reduce the risk of stroke in people with AFib who are 65 years or older or who have other risk factors for stroke (such as diabetes, heart failure, high blood pressure, or stroke). previous stroke or TIA). This study, the Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF), is the first large trial aimed at assessing whether anticoagulation medications can reduce the risk of cognitive decline, stroke, or TIA in adults with AFib but no other risk factors for stroke.
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. Patients should adhere to standard recommendations for cognitive health, including adopting a healthy lifestyle, engaging in activities that stimulate their brain, and maintaining regular physical activity.”
Lena Rivard, M.D., M.Sc., lead author of the study, electrophysiologist at the Montreal Heart Institute and associate professor of medicine at Université de Montréal, Canada
Although the trial was planned to allow a mean follow-up of five years, it was terminated prematurely, with a mean follow-up of 3.7 years, after the Data Safety and Monitoring Committee deemed it futile to continue due to the apparent lack of benefit from the study. the study medication.
The study involved more than 1,200 adults, with an average age of 53, who had AFib but had none of the standard risk factors that would necessitate the prescription of blood thinners. Half of the study participants were randomly selected to receive 15 mg of rivaroxaban daily. The other half were randomly assigned to a placebo group. To include patients with vascular disease, i.e. a condition in which plaque builds up in the blood vessels, in the BRAIN-AF study, a double-dummy design was used. Participants were monitored annually for cognitive decline (a drop of two or more points on the Montreal Cognitive Assessment), stroke or TIA.
After an average of almost four years, the study showed:
- 1 in 5 participants experienced cognitive decline, stroke or TIA. Cognitive decline accounted for 91% of the primary outcome measure; and 1 in 200 had major bleeding.
- The participants had a low incidence of stroke, less than 1 in 100 (0.8%) per year.
- There were no differences in the outcomes of cognitive decline, stroke, or TIA between those taking rivaroxaban and placebo. The rates of these conditions combined were 7% per year for those randomized to rivaroxaban, versus 6.4% per year for those who received placebo.
Rivard said she believes that “in clinical practice, people younger than 65 years of age with AFib tend to be overtreated with anticoagulation therapy, while older people who have indications for anticoagulation are undertreated.” She also said: “Our study supports current guidelines by confirming that younger people with AFib but no other stroke risk factors have a low stroke rate, and that anticoagulation is not useful in reducing the risk of cognitive decline, as reviewed by the Montreal Cognitive Assessment Score.”
The researchers are also analyzing their results (more than 5,700 Montreal Cognitive tests were administered during the trial) using biomarkers and genetic tests collected from most BRAIN-AF participants to better understand cognitive decline in patients with AFib.
“The BRAIN-AF study confirmed a high rate of cognitive decline during follow-up in younger adults. It is not known whether other interventions such as ablation of AFib can positively impact cognition in this population,” Rivard said.
To maximize safety, low-dose rivaroxaban was used in the study. It remains unknown whether a higher dose of rivaroxaban or another molecule would have been effective if the study drug was not.
Study details, background and design:
- BRAIN-AF included 1,235 adults with AFib treated at one of 53 health centers in Canada.
- When participating in the study, participants’ ages ranged from 30 to 62 years, with an average of 53 years. About 26% of participants were female and 96% were white adults.
- None of the participants had the current Canadian standard indications for prescribing anticoagulation therapy for someone with AFib (a previous stroke or TIA, hypertension, diabetes, heart failure, or being 65 years or older). People were excluded from the study if the baseline Mini-Mental State Evaluation showed any degree of dementia, or if they were considered to be at high risk of bleeding due to another medical condition.
- Participants were randomly selected to receive rivaroxaban (15 mg per day) or placebo; those who had vascular disease also received a low dose of aspirin (100 mg per day) in a blinded manner.
- Participants were recruited between April 2015 and November 2023; the last follow-up exams were completed in May 2024.
- Participants were followed for an average of 3.7 years. If they developed any of the standard indications for anticoagulation therapy during that time, they were discontinued from their study medications and switched to standard anticoagulation therapy.
- Participants were monitored for cognitive decline, which was considered significant if there was a drop of 2 points or more on the Montreal Cognitive Assessment, stroke, or TIA with difficulty moving or speaking.
AFib is the most common heart rhythm disorder in the U.S., and its prevalence is expected to increase from approximately 5.2 million in 2010 to 12.1 million in 2030, according to the American Heart Association’s 2024 Heart Disease and Stroke statistics. AFib is an irregular and often rapid heartbeat in which the upper chambers (atria) of the heart do not beat in sync with the lower chambers (ventricles). Some people with AFib have no symptoms, while others have palpitations, light-headedness, dizziness, or chest pain during episodes, which can be short or persistent. It is well known that AFib increases the risk of stroke, and there is mounting evidence that it may contribute to cognitive decline.
Source: