CHICAGO — A randomized placebo-controlled trial testing a direct oral anticoagulant for the prevention of cognitive decline in sufferers with atrial fibrillation (AF) has been halted early for futility.
After a median follow-up of three.7 years, there was no distinction between rivaroxaban 15 mg and placebo for a composite major endpoint that included cognitive decline, stroke, and transient ischemic assault, mentioned Léna Rivard, MD, an electrophysiologist and affiliate professor on the Montreal Heart Institute in Montreal, Quebec, Canada.
When the BRAIN-AF trial was halted by the Data Monitoring Committee, 256 major occasions had occurred, most of which concerned cognitive decline. However, the speed of cognitive decline, outlined as a discount of not less than 2 factors from baseline on the validated Montreal Cognitive Assessment take a look at, was primarily an identical.
“There was no distinction between rivaroxaban and placebo, even with a really excessive fee of cognitive decline detected general,” Rivard mentioned throughout a late-breaker on the American Heart Association (AHA) Scientific Sessions 2024. By the top of follow-up, 18% of examine individuals met the definition of cognitive loss.
Cognitive Decline in 18% of Patients
One limitation of the BRAIN-AF examine was that it enrolled sufferers with a threat for stroke that didn’t meet the rule of thumb standards for oral anticoagulation. This was vital to permit examine individuals to be randomized to placebo.
With this criterion, an age vary of 30-62 years, and exclusions for earlier stroke, hypertension, diabetes, and congestive coronary heart failure, the examine inhabitants was at low threat, however not no threat, for AF occasions. In addition to the noticed charges of cognitive loss that accrued throughout a median follow-up of lower than 4 years, the estimated stroke fee on this low-risk inhabitants was 0.5%-1.0% per yr. The noticed incidence was 2.5%.
The information introduced by Rivard have been on the idea of 1235 sufferers randomized at 53 websites. The median age was 53 years, 78% of examine individuals had a historical past of paroxysmal AF, 96% have been White, and about 25% have been ladies.
There are quite a few explanations for the end result of this examine, together with the truth that sufferers have been too younger and too wholesome, mentioned Andrea M. Russo, MD, an electrophysiologist and professor of medication on the Cooper Medical School at Rowan University in Camden, New Jersey.
In addition, though a 2-year historical past of AF was a examine criterion, the burden of AF, which is perhaps an unbiased threat issue for cognitive loss, was not described, Russo identified.
Overall, this result’s unlikely to rule out microemboli within the pathophysiology of AF-related cognitive decline, however different mechanisms needs to be explored on the idea of the trial outcome, she identified.
Cognitive loss associated to AF “could possibly be a hemodynamic impact,” Russo speculated. With fluctuations in blood movement as a result of irregular rhythm, “hypoperfusion is a chance.”
This examine addresses a extremely related medical query that needs to be the idea for additional work, given the substantial threat for cognitive decline associated to AF in observational research, and is strengthened by the BRAIN-AF information, she defined.
Relatively Low Rivaroxaban Dose
Because of concern about elevated bleeding in a affected person group with out a sign for anticoagulation, the rivaroxaban dose in BRAIN-AF was 15 mg as soon as each day, reasonably than the 20 mg usually used for stroke prophylaxis in sufferers with AF. There have been no deadly bleeding occasions in both group. Although numerically decrease within the rivaroxaban group than within the placebo group, the variations in main bleeding (0.3% vs 0.8%) and stroke (2.5% vs 2.7%) weren’t important.
The examine attracts consideration to the necessity for methods to forestall cognitive decline in sufferers with AF, mentioned Hooman Kamel, MD, vice chair of analysis and chief of neurocritical care at Weill Cornell Medical College in New York City, who was the examine discussant for BRAIN-AF. He known as for a lot extra consideration to be paid to this subject, together with routine measures of cognitive change in trials of recent AF therapies.
Kamel additionally expressed an curiosity in wanting elsewhere for modifiable mechanisms of cognitive decline in sufferers with AF. As an instance, he cited an echocardiographic study that confirmed an affiliation between cognitive decline and left atrial impairment. Although that examine assessed sufferers with atrial myopathy however no AF, it recommended a possible relation between cardiovascular and cerebrovascular pathology that is perhaps extra advanced than emboli within the blood.
He questioned whether or not any managed trial exploring the power of anticoagulation to forestall cognitive decline by stopping microemboli from reaching the mind is possible, now that the advantages of anticoagulation are so effectively established in higher-risk sufferers.
“It could also be too late to check anticoagulation for dementia prevention in AF,” Kamel mentioned.
