AAN 2024 | ARCADIA-CSI: aspirin vs apixaban for the prevention of covert infarcts and cognitive decline

The main ARCADIA trial was seeking to understand whether anticoagulation or antiplatelet therapy would be better in secondary stroke prevention for individuals who had cryptogenic stroke with atrial cardiopathy. They compared those two medications, and the study was stopped early by the Data Safety Monitoring Board for futility because the number of clinical stroke events was the same in both arms.

What Arcadia-CSI (Cognition and Silent Infarction) was seeking to answer was whether atrial cardiopathy produces tiny strokes known as silent or covert infarcts, which in themselves are not clinically important, but in the aggregate, over time have been known to produce cognitive dysfunction. We wanted to know whether aspirin or apixaban would be better protection against silent infarction, and in turn reduce the impact on cognition.

We enrolled 310 individuals who were participating in the ARCADIA trial, who were on the study drug. They were not demented at baseline, and they were at least 90 days from the index stroke for ARCADIA, so that we would be measuring the effect of the drug and not recovery from stroke. The cognitive test battery was administered by the Survey Research Unit at the University of Alabama at Birmingham, because there were 90 hospitals around the United States, and a telephone-based instrument allowed us to give a reliable and valid test battery uniformly to all the centers, again at baseline and then yearly thereafter. If they had a stroke in the main trial (the parent ARCADIA trial) then they were released from our study. But, if they were stroke-free, then we would follow them up to four years.

We found that because the main trial ended early, they ended with about 1.8 months of follow-up. Our median follow-up time was about one year, and so we never really had the opportunity to follow these patients long enough to get a treatment effect. The curves began to diverge because we looked at trajectories of cognition, but there wasn’t enough power for the longer patients in order to be able to reach a conclusion that, in fact, it was protective: so, the study had a null result.

So we’re interested in covert infarction. Overall, we are trying to prevent cognitive decline before it happens. This is because once cognition begins to fail for neurologic reasons, there’s really no way to fully reverse it. Even the latest Alzheimer’s anti-amyloid drugs slow the decline, but do not prevent the decline, and it only works temporarily. So the notion of primary prevention is beginning to take hold. It’s true for the American Academy of Neurology, AARP, American Heart Association, who are all are beginning to look at primary prevention through the lifespan. Doing studies like ARCADIA-CSI and other work that we’re doing in primary prevention, we think is a way to at least reduce the number of cases. The Lancet Commission has stated quite clearly that about 40% of patients with dementia could have been prevented with adequate risk factor management and lifestyle control, so we’re trying to implement that before there is cognitive decline.