Physicians' Academy for Cardiovascular Education

Association of DOACs with adverse outcomes in older patients with AF across frailty subgroups

Frailty and Clinical Outcomes of Direct Oral Anticoagulants Versus Warfarin in Older Adults With Atrial Fibrillation

Literature - Kim DH, Pawar A, Gagne JJ et al. - Annals of Internal Medicine 2021, doi:10.7326/M20-7141

Introduction and methods

Aim of the study

Direct oral anticoagulants (DOACs) have a good safety profile and may therefore be especially suited for older adults with frailty [1]. Choices for anticoagulant therapy (DOACs or warfarin) though are largely driven by risk assessment models for stroke and major bleeding [2-5] and frailty is not taken into account. It is unclear what the role of frailty is when choosing the type of anticoagulant therapy, and anticoagulants are underused in frail patients with AF [6,7]. Therefore, in this study, it was examined how frailty affected the effectiveness of a DOAC (dabigatran, rivaroxaban, or apixaban) on outcomes in older patients with AF.

Study design

This retrospective observational, 1:1 propensity score-matched study used Medicare data of prescription drug use and clinical events in older adults (≥65 years) with AF (including those with frailty). 3 Cohorts were created of AF patients who filled a prescription for 1 of the 3 DOACs or warfarin from the approval date: dabigatran (n=81,863) vs. warfarin (n=256,722), rivaroxaban (n=185,011) vs. warfarin (n=228,028), and apixaban (n=222,478) vs. warfarin (n=206,031). Frailty was measured using a validated claims-based frailty index (CFI) [8-11] (range from 0 to 1) consisting of 93 variables. Nonfrailty was defines as CFI<0.15 prefrailty as CFI of 0.15 to 0.24 and frailty as CFI ≥0.25.

Primary outcome

The primary outcomes was a composite end point of death, ischemic stroke, or major bleeding. Follow-up started the day after initiating the index drug and continued until a study outcome, disenrollment from Medicare, end of the study period, discontinuation of use of the index drug, switch to different anticoagulant, admission to nursing facility, enrollment in hospice care, initiation of dialysis or kidney transplantation.

Main results

Dabigatran versus warfarin

Rivaroxaban versus warfarin

Apixaban versus warfarin


This study using real-world data showed that the DOACs dabigatran and rivaroxaban were associated with lower rates of the composite end point compared to placebo in older patients with AF only in the non-frail group. Apixaban initiators had lower rates of the composite end point across all frailty subgroups.


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