Atrial fibrillation (AF) is the most common cardiac arrhythmia in older patients, and it is associated with an increased risk of stroke, cognitive impairment and dementia.¹ Previous research suggested that people with AF taking oral anticoagulation therapy have a lower risk of dementia, however, the mechanism involved is unknown, cognitive and functional impairment outcomes were not fully evaluated among patients.¹ Since dabigatran offers a more stable anticoagulation status, Professor Bruno Caramelli, Associate Professor of Medicine from University of São Paulo, Brazil, and his colleagues conducted the Cognitive Impairment Related to Atrial Fibrillation (GIRAF) trial to investigate the effects of dabigatran compared with warfarin on the cognitive outcomes in the elderly patients with AF.² GIRAF trial is a two-year randomized, multi-centre, prospective trial in Brazil, which enrolled 200 adults aged over 70 years with confirmed AF and a CHA2DS2-VASc score ≥1.2 Patients with valvular heart disease, dementia, recent bleeding, a history of stroke, and active cancer were excluded.²

The eligible patients were randomly assigned to take dabigatran (150mg twice daily) or warfarin (Adjusted to an international normalized ratio between 2 and 3).² The average time in therapeutic range among warfarin-treated patients was 70%.² Neurologists were blinded to assess the cognitive function of patients at baseline for 2 years using the assessments like the Montreal Cognitive Assessment (MOCA) and mini-Mental State Exam (MMSE) to evaluate global function; the Neuropsychological Battery (NTB) to test the attention memory, language and executive functions; and the computer-generated neuropsychological test (CGNT) to evaluate sustained, selective and divided attention.² Additionally, patients also underwent brain MRI to identify potential cerebrovascular events.²

Results showed that only the MOCA-score had a significant difference between groups with a more favorable effect in patients taking warfarin (Difference of -0.96, 95% CI: -1.8 to -0.13, p=0.02). There was no difference observed between the groups at 2 years in the changes of specific cognitive domains such as memory, executive function, language, or attention as stated by Prof. Caramelli.² It is believed larger study should be able to demonstrate difference between the two drugs, at least this trial showed us there are more mechanisms to drive cognitive decline, and that it may be more than just the choice of anticoagulation.

Prof. Caramelli stressed that regardless of which anticoagulant to choose, it is important to take it correctly, with a high rate of adherence. Otherwise, the results in terms of cognitive outcomes might not be the same as seen in GIRAF. And when it comes to selecting an oral anticoagulant for older patients with AF, the higher risk of bleeding with warfarin is an important consideration. If the patient is more prone to suffer a hemorrhagic complication, dabigatran may be a more optimal choice to achieve favorable outcomes.

Prof. Caramelli concluded that in older patients with AF or atrial flutter who did not present major cerebrovascular events and were adequately treated with warfarin or dabigatran for 2 years, there was no difference in the majority of the cognitive outcomes.