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. 2023 Mar 25;7(3):100129.
doi: 10.1016/j.rpth.2023.100129. eCollection 2023 Mar.

Frailty and subsequent adverse outcomes in older patients with atrial fibrillation treated with oral anticoagulants: The Shizuoka study

Shiori Nishimura  1   2 , Hiraku Kumamaru  1   2 , Satoshi Shoji  2   3 , Eiji Nakatani  2 , Hiroyuki Yamamoto  1   2   4 , Nao Ichihara  1   2 , Alexander T Sandhu  5 , Yoshiki Miyachi  2 , Hiroaki Miyata  1   2   4 , Shun Kohsaka  1   2   3
Affiliations

Frailty and subsequent adverse outcomes in older patients with atrial fibrillation treated with oral anticoagulants: The Shizuoka study

Shiori Nishimura et al. Res Pract Thromb Haemost. .

Abstract

Background: In older patients with atrial fibrillation (AF), frailty is frequently prevalent. However, the prognostic value of frailty for adverse events after initiation of oral anticoagulants (OACs) is unclear.

Objectives: We assessed whether frailty at the time of OAC initiation is associated with subsequent bleeding or embolic events.

Methods: We extracted patients aged ≥65 years with nonvalvular AF in whom OACs were initiated from a universal administrative claims database incorporating primary and hospital care records in Shizuoka, Japan, between 2012 and 2018. Frailty was assessed using the electronic frailty index (eFI). The association of frailty with bleeding events and ischemic stroke/transient ischemic attack were evaluated using the Fine-Gray model and restricted cubic spline model.

Results: Among 12,585 patients with AF, 7.8% were categorized as fit, 31.5% as mildly frail, 34.8% as moderately frail, and 25.9% as severely frail. The risk of bleeding was associated with a higher eFI (adjusted subdistribution hazard ratio [95% CI] for fit or mild frailty: 1.15 [1.02-1.30]; moderate frailty: 1.42 [1.24-1.61]; and severe frailty: 1.86 [1.61-2.15]), whereas the association was weaker for ischemic stroke/transient ischemic attack. The spline models demonstrated that the relative hazard for bleeding increased steeply with increasing eFI.

Conclusion: Patients with frailty in whom OAC therapy is initiated have higher risk of bleeding, highlighting the importance of discussing this increased risk with patients with AF who have frailty and assessing frailty at the time of OAC initiation.

Keywords: anticoagulants; atrial fibrillation; frailty; hemorrhage; stroke.

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Figures

Figure 1
Figure 1
Study design timeline. CHA2DS2-VASc, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, valvular disease, age 65 to 74; HAS-BLED, age>65 years, hypertension, abnormal renal and liver function, prior stroke, bleeding history or predisposition, labile international normalized ratio, and drugs/alcohol concomitantly.
Figure 2
Figure 2
Associations between frailty and direct oral anticoagulant dose. DOAC, direct oral anticoagulant; eFI, electronic frailty index.
Figure 3
Figure 3
Cumulative incidence of outcomes stratified by electronic frailty index categories. Note: Shaded bands indicated 95% CIs. The y-axis ranges from 0 to 70%, indicating the cumulative incidence of bleeding, and from 0 to 8% indicating the cumulative incidence of ischemic stroke/transient ischemic attack and major bleeding. TIA, transient ischemic attack.
Figure 4
Figure 4
Associations between electronic frailty index and outcomes (eFI). Note: The model was adjusted for sex, medical history, and medications. Subdistribution hazard ratios with 95% CIs are plotted. An eFI score of 0.12 (cutoff score between fit and mild frailty) was the reference standard. Bleeding events were defined as any outpatient or inpatient bleeding event. The vertical dotted lines show thresholds for the percentiles of eFI value. eFI, electronic frailty index; sHR, subdistribution hazard ratio; TIA, transient ischemic attack.
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