Physicians' Academy for Cardiovascular Education

Comparing anticoagulants for AF: Which OAC is best for patients with dementia?

Comparative Effectiveness and Safety of Oral Anticoagulants by Dementia Status in Older Patients With Atrial Fibrillation

Literature - Lin KJ, Singer DE, Bykov K, et al. - JAMA Netw Open. 2023 Mar 1;6(3):e234086. doi: 10.1001/jamanetworkopen.2023.4086

Introduction and methods


To reduce the risk of embolic stroke, most older patients with AF should be treated with oral anticoagulation (OAC) [1-6]. While there is a need for an optimal stroke prevention strategy for AF patients who are living with dementia, this population was greatly underrepresented in RCTs showing the efficacy and safety of direct OACs versus warfarin [7-10].

Aim of the study

The authors examined the comparative safety and effectiveness of 4 OACs (apixaban, dabigatran, rivaroxaban, and warfarin) by assessing the risks of ischemic stroke and major bleeding by dementia status in older AF patients.


In this retrospective comparative effectiveness study, data from 3 large nationwide claims databases in the USA (Optum Clinformatics Data Mart, IBM MarketScan Research Database, and Medicare fee-for-service Parts A, B, and D) were pooled. The dataset comprised 1,160,462 patients ≥65 years diagnosed with AF (mean age: 77.4 years; SD: 7.2) who filled a new prescription for a specific OAC; 7.9% of them had a dementia diagnosis. Based on the medication, the authors established 3 comparative cohorts: warfarin versus apixaban (n=501,990), dabigatran versus apixaban (n=126,718), and rivaroxaban versus apixaban (n=531,754). To adjust for potential confounding, 1:1 propensity score matching was used..


The primary endpoint was a composite outcome of ischemic stroke or major bleeding events in the 6 months following the OAC dispensing date. Secondary endpoints included the individual components of the primary endpoint (i.e., ischemic stroke and components of major bleeding events, including gastrointestinal bleeding, other extracranial bleeding, and intracranial hemorrhage) and all-cause mortality.

Main results

Warfarin versus apixaban

Dabigatran versus apixaban

Rivaroxaban versus apixaban


In this retrospective comparative effectiveness study comprising >1 million AF patients aged ≥65 years in the USA, treatment with apixaban was associated with a lower rate of ischemic stroke or major bleeding on the relative scale compared with dabigatran, rivaroxaban, or warfarin, mostly irrespective of dementia status. However, in terms of absolute rate reduction, the magnitude of the benefit associated with apixaban was greater in patients with dementia compared with those without dementia, particularly for major bleeding. The authors believe “[t]hese results support the use of apixaban for anticoagulation therapy in vulnerable patients with frailty, particularly those living with dementia.”


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Find this article online at JAMA Netw Open.

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