Physicians' Academy for Cardiovascular Education

Very old AF patients in Japan benefit from very low-dose DOAC

Effect of 15-mg Edoxaban on Clinical Outcomes in 3 Age Strata in Older Patients With Atrial Fibrillation – A Prespecified Subanalysis of the ELDERCARE–AF Randomized Clinical Trial

Literature - Kuroda M, Tamiya E, Nose T, et al. - JAMA Cardiol. 2022 Apr 13;e220480. doi:10.1001/jamacardio.2022.0480

Introduction and methods


To prevent cardioembolic stroke in patients with AF, clinical guidelines recommend using direct oral anticoagulants (DOACs ), even in the elderly [1,2]. In the ELDER-CARE-AF (Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients) trial, very low-dose edoxaban (15 mg) reduced the incidence of stroke or systemic embolism compared to placebo in older Japanese patients (≥80 years) with AF, without a significant difference in bleeding between the two arms. However, the effectiveness and safety of DOACs in extremely old AF patients (≥90 years) with a high bleeding risk still need to be elucidated.

Aim of the study

The study aim was to assess the effects of very low-dose edoxaban (15 mg) across three age strata (80–84 years, 85–89 years, and ≥90 years) of AF patients who took part in the ELDERCARE-AF trial.


This was a prespecified subanalysis of the ELDERCARE-AF trial. In this multicenter, double-blind, placebo-controlled, phase 3 RCT conducted in Japan from August 2016 to December 2019, 984 AF patients who were not considered candidates for a standard OAC regimen were randomized (1:1 ratio) to edoxaban 15 mg once daily or placebo [3].

Inclusion criteria were: aged ≥80 years; history of AF documented within 1 year of consent; CHADS2 score ≥2 points; and ineligibility for standard-dose OACs due to increased bleeding risk (f.e., creatinine clearance <30 mL/min, or history of bleeding from a critical area/organ or gastrointestinal bleeding). Exclusion criteria were moderate-severe mitral stenosis and/or mechanical heart valves, among others.


The primary efficacy endpoint was the composite outcome of stroke and systemic embolism. The primary safety endpoint was major bleeding according to the International Society on Thrombosis and Hemostasis criteria.

Main results




In Japanese AF patients aged ≥80 years who were not eligible for standard OAC therapy, edoxaban 15 mg was superior to placebo in preventing stroke or systemic embolism in all tree age strata. The numbers of major bleeding and major or clinically relevant nonmajor bleeding events were not significantly, albeit numerically, higher with edoxaban. The authors warn that care should be taken when applying these results to other ethnic populations.


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Find this article online at JAMA Cardiol.

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