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Outcomes and Safety of Very-Low-Dose Edoxaban in Frail Patients With Atrial Fibrillation in the ELDERCARE-AF Randomized Clinical Trial

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 co...

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Autores principales: Akashi, Shintaro, Oguri, Mitsutoshi, Ikeno, Eiichiro, Manita, Mamoru, Taura, Junki, Watanabe, Saori, Hayashi, Takuya, Akao, Masaharu, Okumura, Ken, Akishita, Masahiro, Yamashita, Takeshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399878/
https://www.ncbi.nlm.nih.gov/pubmed/35997978
http://dx.doi.org/10.1001/jamanetworkopen.2022.28500
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author Akashi, Shintaro
Oguri, Mitsutoshi
Ikeno, Eiichiro
Manita, Mamoru
Taura, Junki
Watanabe, Saori
Hayashi, Takuya
Akao, Masaharu
Okumura, Ken
Akishita, Masahiro
Yamashita, Takeshi
author_facet Akashi, Shintaro
Oguri, Mitsutoshi
Ikeno, Eiichiro
Manita, Mamoru
Taura, Junki
Watanabe, Saori
Hayashi, Takuya
Akao, Masaharu
Okumura, Ken
Akishita, Masahiro
Yamashita, Takeshi
author_sort Akashi, Shintaro
collection PubMed
description 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.
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spelling pubmed-93998782022-09-06 Outcomes and Safety of Very-Low-Dose Edoxaban in Frail Patients With Atrial Fibrillation in the ELDERCARE-AF Randomized Clinical Trial Akashi, Shintaro Oguri, Mitsutoshi Ikeno, Eiichiro Manita, Mamoru Taura, Junki Watanabe, Saori Hayashi, Takuya Akao, Masaharu Okumura, Ken Akishita, Masahiro Yamashita, Takeshi JAMA Netw Open Original Investigation 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. American Medical Association 2022-08-23 /pmc/articles/PMC9399878/ /pubmed/35997978 http://dx.doi.org/10.1001/jamanetworkopen.2022.28500 Text en Copyright 2022 Akashi S et al. JAMA Network Open. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the CC-BY-NC-ND License.
spellingShingle Original Investigation
Akashi, Shintaro
Oguri, Mitsutoshi
Ikeno, Eiichiro
Manita, Mamoru
Taura, Junki
Watanabe, Saori
Hayashi, Takuya
Akao, Masaharu
Okumura, Ken
Akishita, Masahiro
Yamashita, Takeshi
Outcomes and Safety of Very-Low-Dose Edoxaban in Frail Patients With Atrial Fibrillation in the ELDERCARE-AF Randomized Clinical Trial
title Outcomes and Safety of Very-Low-Dose Edoxaban in Frail Patients With Atrial Fibrillation in the ELDERCARE-AF Randomized Clinical Trial
title_full Outcomes and Safety of Very-Low-Dose Edoxaban in Frail Patients With Atrial Fibrillation in the ELDERCARE-AF Randomized Clinical Trial
title_fullStr Outcomes and Safety of Very-Low-Dose Edoxaban in Frail Patients With Atrial Fibrillation in the ELDERCARE-AF Randomized Clinical Trial
title_full_unstemmed Outcomes and Safety of Very-Low-Dose Edoxaban in Frail Patients With Atrial Fibrillation in the ELDERCARE-AF Randomized Clinical Trial
title_short Outcomes and Safety of Very-Low-Dose Edoxaban in Frail Patients With Atrial Fibrillation in the ELDERCARE-AF Randomized Clinical Trial
title_sort outcomes and safety of very-low-dose edoxaban in frail patients with atrial fibrillation in the eldercare-af randomized clinical trial
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399878/
https://www.ncbi.nlm.nih.gov/pubmed/35997978
http://dx.doi.org/10.1001/jamanetworkopen.2022.28500
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