For patients with nonvalvular atrial fibrillation (AFib), taking a direct oral anticoagulant (DOAC) instead of warfarin may cut the risk of dementia by 15 to 20 percent, according to a large database study published Nov. 2 in the Journal of the American Heart Association.
Researchers used two healthcare claims databases to identify almost 470,000 U.S. patients with AFib who received prescriptions for warfarin or one of three DOACs: dabigatran, rivaroxaban or apixaban. They compared each individual medication to one another, using propensity-score matching to balance patient characteristics as much as possible.
In comparisons with warfarin, each DOAC was associated with a lower risk of dementia during the follow-up period, which ranged from 0.7 to 2.2 years depending on which drugs were being evaluated. Rivaroxaban and dabigatran were linked to 15 percent reductions in dementia, while apixaban was tied to a 20 percent risk reduction.
The authors noted no significant difference in dementia incidence in head-to-head comparisons between the DOACs.
“Our findings suggest the following: (1) DOACs may be superior to warfarin with respect to outcome of dementia, which is considered as an important adverse outcome of (AFib); and (2) future risk of dementia does not appear to be influenced by choice of DOAC. Therefore, DOAC choice should be driven by other efficacy, safety, and preference considerations,” wrote corresponding author Alvaro Alonso, MD, PhD, with Emory University, and colleagues.
Alonso et al. noted their results should be interpreted with caution because the retrospective, nonrandomized nature of the study could allow for misclassification and residual confounding—despite the use of propensity-matching and sensitivity analyses.
Still, they hypothesized DOACs could cut down on microbleeds from suboptimal anticoagulation with warfarin, which stems from common fluctuations in therapeutic levels.
“These microbleeds could cause chronic cerebral injury and finally lead to dementia,” Alonso and coauthors wrote. “Moreover, DOAC users experience lower risk of intracranial bleeding compared with warfarin users. As shown in pivotal clinical trials, dabigatran, rivaroxaban, and apixaban were all reported noninferior in preventing ischemic stroke or systemic embolism, and they had lower rates of intracranial hemorrhage compared with warfarin.”
The reduction in dementia risk with DOACs was consistent regardless of patient age, sex and baseline stroke risk, the researchers reported. They said the study results could be particularly useful in guiding anticoagulation decisions among AFib patients at higher risk for poor cognitive outcomes, including older individuals and those already experiencing mild cognitive impairment.
Alonso and colleagues noted additional studies are needed to assess the long-term impacts of anticoagulant choice on dementia outcomes—especially for apixaban, which was approved by the FDA later than the other DOACs and therefore has shorter follow-up periods available for real-world analysis.