Akashi S, Oguri M, Ikeno E, et al. Outcomes and Safety of Very-Low-Dose Edoxaban in Frail Patients With Atrial Fibrillation in the ELDERCARE-AF Randomized Clinical Trial. JAMA Netw Open. 2022 Aug 1;5(8):e2228500. doi: 10.1001/jamanetworkopen.2022.28500. (Original study)

Importance: The prevalence of atrial fibrillation (AF) increases with age and is more common in frail patients. However, data are lacking on outcomes of oral anticoagulants (OACs) in very elderly patients with AF with frailty, who are ineligible for standard anticoagulant treatment.

Objective: To compare very-low-dose edoxaban (15 mg daily) vs placebo across frailty status, including each of 5 frailty assessment parameters, among patients with AF involved in the ELDERCARE-AF (Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients) trial.

Design, Setting, and Participants: This is a cohort study using data from ELDERCARE-AF, a multicenter, randomized, double-blind, placebo-controlled phase 3 study of Japanese patients with AF aged 80 years or older who were ineligible for OACs at doses approved for stroke prevention because of their high bleeding risks. Eligible patients were randomly assigned (1:1) to receive edoxaban or placebo. The study duration was from August 5, 2016, to November 5, 2019, with the last patient followed up on December 27, 2019. Data analysis was performed from February 2021 to February 2022.

Exposure: Edoxaban (15 mg) once daily or placebo.

Main Outcomes and Measures: The primary efficacy end point was the composite of stroke or systemic embolism, and the primary safety end point was major bleeding.

Results: A total of 984 patients were randomly assigned to treatment (492 each to the edoxaban and placebo groups); 944 patients (402 frail patients [42.6%]; 542 nonfrail patients [57.4%]; mean [SD] age, 86.6 [4.3] years; 541 women [57.3%]) were included in this analysis. In the placebo group, the estimated event rates (SE) for stroke or systemic embolism were 7.1% (1.6%) per patient-year in the frail group and 6.1% (1.3%) per patient-year in the nonfrail group. Edoxaban was associated with lower event rates for stroke or systemic embolism with no interaction with frailty status or frailty assessment parameters. Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than in the placebo group, and no heterogeneity was observed with frailty status. Although both all-cause death and net clinical composite outcome occurred more frequently in the frail group than in the nonfrail group, there was no association with frailty status between the edoxaban and placebo groups.

Conclusions and Relevance: Regardless of frailty status, among Japanese patients with AF aged 80 years or older who were ineligible for standard OACs, once-daily 15-mg edoxaban was associated with reduced incidence of stroke or systemic embolism and may be a suitable treatment option for these patients.

Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Internal Medicine 6 / 7
Geriatrics 6 / 7
Cardiology 5 / 7
Comments from MORE raters

Cardiology rater

This study is a re-analysis of the ELDER CARE AF trial of low-dose edaxaban for atrial fibrillation (AF) in the very elderly, stratified by various indices of frailty. It showed that edoxaban was generally safe and effective in frail and non-frail groups. It will be of interest to geriatricians and physicians caring for the very elderly with AF.

Family Medicine (FM)/General Practice (GP) rater

This study should be repeated in more ethnically diverse populations before the results are used to formulate clinical recommendations and guidelines.

General Internal Medicine-Primary Care(US) rater

Very interesting result - I await results in a US population.

General Internal Medicine-Primary Care(US) rater

An important clinical concern. This information should improve information sharing and decision-making between clinicians and their patients who have frailty and atrial fibrillation.

Internal Medicine rater

It is unclear what the article's primary aim was and how it benefits clinical care. It would be interesting to see what the comparison is with an LAO device or even low-dose aspirin. Given that edoxaban increased bleeding events, I am not sure how it is helpful here and how it will change practice.
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