Dabigatran or warfarin: Choice does not matter in GIRAF

The choice of oral anticoagulant does not appear to influence the outcome in terms of preserving cognitive function in older patients with atrial fibrillation (AF), the GIRAF* study has shown.

After 2 years of treatment, scores on a variety of cognitive outcomes were similar between patients with AF receiving dabigatran or warfarin. “It’s possible that cognitive decline is related to the formation of small blood clots in the brain, which may be attacked by effective medications that prevent blood clots,” said lead study author Dr Bruno Caramelli, associate professor of medicine, University of Sao Paulo, Brazil.

“Remember, dabigatran was the one NOAC that was actually statistically better than warfarin in reducing ischaemic stroke, so the thought was maybe it’d do better at preventing dementia,” commented Dr Christian Ruff, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, US. “But there ended up being no difference in neuropsychologic testing, the onset of cognitive impairment, or dementia in these patients.”

“The findings tell us there likely is a more complicated story to dementia and AF, and the choice of anticoagulant doesn’t necessarily influence that selection,” Ruff said.

No significant difference

Investigators assessed multiple cognitive outcomes in 200 patients in Brazil with AF or atrial flutter, who had a CHA₂DS₂-VASc score >1, and were 70 years or older. They were randomized to dabigatran 110 mg or 150 mg twice daily or warfarin once daily adjusted to an INR of 2–3. [AHA 2021, abstract LBS.03]

Cognitive outcomes were evaluated at baseline and 2 years, using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Exam, Geriatric Depression Scale, semantics verbal fluency, phonemic verbal fluency, Digit Symbol Substitution Test, Boston Naming Test short version, and clock-drawing test. Patients also had brain MRI at both time points to identify potential cerebrovascular events.

At the 2-year cognitive evaluation, there were more haemorrhagic complications and related deaths with warfarin. There was not much difference on any of the cognitive assessments between trial arms, except for MoCA (p=0.02), which favoured warfarin. But Caramelli said this could only be due to chance.

Looking at individual cognitive domains, there were no significant differences between dabigatran and warfarin in changes in memory, executive function, language, or attention.

Dr Jim Cheung from Weill Cornell Medicine, New York, NY, who was unaffiliated with the study, said a larger trial might show a difference between the two anticoagulants.  “But what the study tells me is that the mechanism behind AF-associated cognitive decline is probably multifactorial.”

“We need to better understand what are the actual mechanisms that drive cognitive decline … it may be more than just anticoagulant choice,” he added. “Do we think about rhythm control for certain patients as opposed to focusing only on AF?”

“Cognitive aspects are important to AF patients,” said Caramelli. “Our findings could help guide decisions on which oral anticoagulant to prescribe.” Regardless of the choice, it is crucial to take the drug correctly, with good adherence, he pointed out.

For older patients with AF, bleeding with warfarin may be an important consideration. “In patients likely to have haemorrhagic complication, dabigatran may be a better option,” Caramelli said.