Apixaban Useful for Anticoagulation Therapy for Older Adults with Dementia, Atrial Fibrillation

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New data suggest that older dementia patients who also have dementia are recommended to take apixaban, an oral anticoagulant.

The oral anticoagulant (OAC) apixaban’s absolute risks are lower than those of other OACs among patients with dementia compared to those without dementia, according to new findings, suggesting patients with dementia and atrial fibrillation (AF) may benefit from apixaban.1

Although randomized clinical trials (RCTs) have established both the effectiveness and safety of direct oral OACs in comparison to warfarin for patients with AF, older adults with frailty or dementia had not been adequately represented in these studies.

This research was conducted to expand upon what little RCT data there is on the role of dementia in the efficacy and safety of OACs. It was authored by Kueiyu Joshua Lin, MD, ScD, MPH, from the Department of Medicine at Brigham and Women’s Hospital and Harvard Medical School.

“We aimed to examine the comparative safety and effectiveness of specific OACs by assessing the risks of ischemic stroke and major bleeding events by dementia status among older patients with AF,” Lin and colleagues wrote.

Background and Findings

The investigators used a comparative effectiveness study, during which they analyzed data from 3 different sources: the Optum Clinformatics Data Mart, Medicare claims databases maintained by the Centers for Medicare & Medicaid Services (inpatient, outpatient, and pharmacy), and IBM MarketScan Research Database.

The team’s research focused on participants who were aged 65 years or older and had AF, with the researchers using 1:1 propensity score matching.

For inclusion in the study, participants had to meet certain criteria, including having 1 or more diagnoses of AF during the trial’s baseline assessment period and being enrolled in medical and pharmacy coverage for a minimum of 365 days.

The researchers excluded those who received hospice care, had major bleeding within the past 30 days, had other indications for OAC, or had valvular heart diseases or end-stage kidney or liver disease in the year prior to the baseline assessment period.

The main exposures analyzed by the investigators were apixaban, rivaroxaban, dabigatran, or warfarin, and the team used random-effects meta-analyses to pool data across their databases.

The composite endpoint evaluated was ischemic stroke or major bleeding events occurring during the 6-month period after OAC initiation.

The investigators enrolled 1,160,462 older adult patients with AF and a mean age of 77.4 years, among whom 80.5% were reported as White and 50.2% were reported as male. They established 3 comparative new-user study cohorts: warfarin versus apixaban, dabigatran versus apixaban, and rivaroxaban versus apixaban.

Participants with dementia showed higher composite end-point rates compared with apixaban users, regardless of a dementia diagnosis on the hazard ratio scale, with rates of 95.7, 84.5, and 87.4 events per 1000 person-years (PYs) respectively, compared to 64.2 events per 1000 PYs for warfarin, 54.9 events per 1000 PYs for dabigatran, and 68.5 events per 1000 PYs for rivaroxaban.

Despite this fact, the rate difference scale showed substantial differences. The benefits associated with apixaban were similar in all 3 of the comparisons, but the magnitude of the benefits differed substantially on the rate difference scale.

The adjusted rate difference estimates of the composite outcome for dabigatran versus apixaban users were 29.6 events per 1000 PYs in patients with dementia compared to 5.8 events per 1000 PYs in patients without dementia.

Similarly, for rivaroxaban vs apixaban users, the adjusted rate difference estimates of the composite outcome were 20.5 events per 1000 PYs in patients with dementia compared to 15.9 events per 1000 PYs in patients without dementia.

Overall, the investigators noted that apixaban had a more distinct pattern for major bleeding than for ischemic stroke.

“The increased absolute risks associated with other OACs compared with apixaban were greater among patients with dementia than those without dementia, particularly for major bleeding,” they wrote. “These findings support the use of apixaban for anticoagulation therapy in patients living with dementia who have AF.”


  1. Lin KJ, Singer DE, Bykov K, et al. Comparative Effectiveness and Safety of Oral Anticoagulants by Dementia Status in Older Patients With Atrial Fibrillation. JAMA Netw Open. 2023;6(3):e234086. doi:10.1001/jamanetworkopen.2023.4086.