Rivaroxaban fails to prevent cognitive decline, stroke in younger adults with AF
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Key takeaways:
- The BRAIN-AF trial enrolled adults younger than 65 years who had atrial fibrillation but no other risk factors for stroke.
- Results suggest stroke risk is low in younger patients.
CHICAGO — In the BRAIN-AF trial, daily rivaroxaban did not reduce the incidence of cognitive decline, stroke or transient ischemic attack, compared with placebo, among younger patients with atrial fibrillation and low stroke risk.
BRAIN-AF is the first large trial to focus on assessing whether a blood thinner can reduce risk for cognitive decline, stroke or TIA among adults younger than 65 years with a diagnosis of AF but no other risk factors for stroke, according to the researchers.
The trial enrolled more than 1,200 adults aged 30 to 62 years, with the average age of participants at 53 years.
“[We included] patients with AF and low risk of stroke, which means they don’t require anticoagulation when you look at the guidelines,” Lena Rivard, MD, MSc, electrophysiologist at Montreal Heart Institute and associate professor of medicine at University of Montreal, said during a press conference at the American Heart Association Scientific Sessions.
However, the researchers found that anticoagulation therapy — in this trial, rivaroxaban (Xarelto, Janssen/Bayer) 15 mg daily — did not reduce risk for cognitive impairment or stroke/TIA in this population.
Risk in younger adults
Multiple observational studies have shown that anticoagulation decreases the risk for dementia in patients with AF, Rivard said during the press conference.
For BRAIN-AF, 1,235 patients (25% women; 95% white) at 53 sites in Canada were randomly assigned to daily rivaroxaban 15 mg or placebo. No participants had current Canadian standard indications for oral anticoagulation beyond AF, which included prior stroke/TIA, high BP, diabetes or HF. All patients underwent baseline assessment with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA); MoCA assessments were repeated yearly and both MMSE and MoCA at the final visit.
The trial was planned for an average follow-up of 5 years, but it was terminated early at an average follow-up of 3.7 years after the data safety and monitoring board recommended stopping the trial due to a lack of benefit from the study medication.
During 3.7 years of follow-up, 5,765 MoCA assessments were performed and 256 primary endpoints occurred. The primary composite outcome included cognitive decline (defined by 2-point reduction in MoCA score vs. baseline), stroke or TIA. Cognitive decline accounted for 91% of the primary outcome events.
The primary outcome occurred in 21% of the group assigned rivaroxaban compared with 20% of the group assigned placebo (HR = 1.1; 95% CI, 0.86-1.4; P = .46), Rivard said.
Regarding secondary outcomes, stroke, TIA or systemic embolism occurred in 2.5% of the rivaroxaban group vs. 2.7% of the placebo group (HR = 0.92; 95% CI, 0.5-1.84). Major bleeding occurred in 0.3% vs. 0.8%, respectively, and there were no occurrences of fatal bleeding during the trial. Ten patients died during the trial (six in placebo group) and the cause was primarily CVD, Rivard said.
The researchers noted several limitations of the trial, including cognitive decline solely determined by the MoCA test, enrollment of primarily white and male patients, and inability to extrapolate the findings to other populations.
‘Interplay between heart health and brain health’
During a discussion after the presentation, Hooman Kamel, MD, MS, the Helen and Albert Moon Professor and vice chair for research, department of neurology, Weill Cornell Medicine, said the BRAIN-AF trial “answers a really important question that there’s no role for expanding our current indications for anticoagulation to people ... who generally are younger and healthier to try to preserve brain health.”
Moreover, “I think it may just be too late to test anticoagulation further for dementia prevalence in atrial fibrillation because you really have to target a population that has a very high burden of atrial fibrillation ... and vascular comorbidities, and that’s a population that we generally currently anticoagulated because of so much evidence to support its role in stroke prevention,” Kamel said.
Looking forward, Kamel said there are many exciting emerging therapies coming, and noted that “it makes sense for those treatment strategies to try to incorporate broader measures of brain health than just stroke.”
In the future, “we can imagine a lot of interplay between heart health and brain health in this space,” Kamel said. “I think [BRAIN-AF] really moves the field forward in terms of the role of anticoagulation in the younger, healthier atrial fibrillation population, but we still have a lot of work to do to try to preserve brain health in older atrial fibrillation patients with vascular risk factors.”
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Rivard L. LBS.03. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2024; Chicago.
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