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Two Anticoagulants -- When Used Correctly -- Similarly Protective Against Dementia

— GIRAF trial tested warfarin versus dabigatran in older Afib patients

MedpageToday

Cognitive outcomes were mostly the same between dabigatran (Pradaxa) and warfarin (Coumadin) users with nonvalvular atrial fibrillation (Afib) and no baseline dementia, a randomized trial showed.

In the GIRAF trial, people ages 70 and older assigned to either drug had no large differences in four cognitive test scores at 2 years:

  • Mini-Mental State Exam: -0.69 with dabigatran vs -0.57 with warfarin (P=0.75)
  • Montreal Cognitive Assessment: -0.39 vs +0.58 (P=0.02)
  • Neuropsychological battery: +0.02 vs -0.03 (P=0.40)
  • Computer-generated neuropsychological test: -0.06 vs +0.09 (P=0.06)

As for specific cognitive domains, there were trends for better memory with the direct oral anticoagulant (DOAC) and better attention with warfarin (P=0.07), but these may be attributed to chance in the 200-person study, reported Bruno Caramelli, MD, PhD, of University of Sao Paulo in Brazil, at the American Heart Association (AHA) virtual meeting.

"Cognitive decline is hugely important for patients and their social networks. This study demonstrates that different anticoagulation regimes protect against cognitive decline in a similar way," commented Paulus Kirchhof, MD, of University Heart and Vascular Center UKE Hamburg in Germany.

"While there are several important overall benefits of dabigatran over warfarin for the management of patients with AF [Afib], this study would suggest dabigatran is not superior to warfarin with respect to cognitive outcomes," said Jim Cheung, MD, of Weill Cornell Medicine/New York-Presbyterian Hospital in New York City, who was not involved with the trial.

Mechanisms underlying the association between Afib and cognitive decline are multifactorial, he emphasized.

"Potential mechanisms for AF-related cognitive decline include silent cerebral infarction, cerebral hypoperfusion, and microbleeds. Therefore, the singular impact of the beneficial effects of DOACs over warfarin for reducing embolic stroke may be blunted by other factors that contribute to AF-associated cognitive decline," Cheung stated.

Notably, the time spent in therapeutic range was 69.9% for the warfarin group in GIRAF -- close enough to the 70% threshold for quality anticoagulation.

"Historical cohort studies have suggested that subtherapeutic warfarin use may be associated with increased dementia and that DOAC use may be associated with less dementia. However, these retrospective studies are limited by fact that the confounding presence of baseline dementia, and its associated comorbidities, can complicate maintenance of a therapeutic regimen and can impact the decision to use warfarin instead of DOACs by treating clinicians," Cheung noted.

"A better understanding of the dominant pathophysiology behind AF-associated cognitive decline and dementia is needed to guide the best treatment for improving cognitive outcomes in AF patients; whether such treatment should focus on stroke prevention or rhythm management remains to be seen," he added.

Ultimately, Afib patients need to be taking the correct dose of their medication, stressed AHA press conference discussant Biykem Bozkurt, MD, PhD, of Baylor College of Medicine in Houston. "When done right, according to the guidelines, the efficacy [between dabigatran and warfarin] is very comparable."

was an open-label trial of 200 people with Afib or atrial flutter, excluding people with valvular heart disease, dementia, recent bleeding, a history of stroke, and active cancer.

Participants were randomized to dabigatran (110 mg or 150 mg twice a day) or warfarin (targeting an international normalized ratio of 2-3 once daily). At baseline and at 2 years, blinded neurologists performed cognitive testing using the four aforementioned tools.

Overall, patient age was an average of 75 and 60% were men. The two study arms shared similar baseline characteristics.

Caramelli acknowledged that attrition was high and unbalanced in the study: only 83 people in the dabigatran group and 66 in the warfarin group made it to their 2-year cognitive evaluation.

Warfarin users tend to have more hemorrhagic complications, he acknowledged. "If you're a patient more prone to suffer a hemorrhagic complication, maybe this is the case to prefer the other drug, dabigatran."

  • author['full_name']

    Nicole Lou is a reporter for app, where she covers cardiology news and other developments in medicine.

Disclosures

GIRAF was supported by Boehringer Ingelheim.

Caramelli had no disclosures.

Bozkurt reported ties to Abbott, scPharmaceuticals, Amgen, Vifor, Relypsa, Respicardia, and LivaNova.

Primary Source

American Heart Association

Caramelli B "Dabigatran versus warfarin on cognitive outcomes in nonvalvular atrial fibrillation: results of the GIRAF trial" AHA 2021.