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Vol. 74. Issue 1.
Pages 97-99 (January 2021)
Vol. 74. Issue 1.
Pages 97-99 (January 2021)
Scientific letter
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High use of direct oral anticoagulants in elderly patients with atrial fibrillation: data from the REFLEJA registry
Uso amplio de anticoagulantes de acción directa en pacientes ancianos con fibrilación auricular: datos del registro REFLEJA
Javier Torres Llergo
Corresponding author

Corresponding author:
, María Rosa Fernández Olmo, Magdalena Carrillo Bailén, Miguel Puentes Chiachio
Servicio de Cardiología, Hospital Universitario de Jaén, Jaén, Spain
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Table 1. Clinical and epidemiological characteristics of the study population by age
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To the Editor,

The prevalence of atrial fibrillation (AF) increases with age and peaks at the age of ≥80 years (17.7%).1 Decisions on oral anticoagulation (OAC) therapy are challenging in patients of this age due to a higher stroke and bleeding risk. Although direct oral anticoagulants (DOACs) have been shown to be an attractive option for elderly patients—they are at least as effective as vitamin K antagonists and substantially reduce intracranial hemorrhage—they are clearly underused.2

The aim of this study was to assess the use of DOACs in a contemporary clinical series of patients aged ≥80 years and to analyze predictors of DOAC use and the influence of age on choice of doses.

The REFLEJA AF study is a prospective registry of 1039 consecutive outpatients with nonvalvular AF (NVAF) evaluated between October 2017 and June 2018 at a single hospital in Jaen, Spain. The registry includes all patients aged ≥18 years with NVAF evaluated by the cardiology unit. We compared the baseline characteristics of patients aged <80 years and ≥80 years by bivariate analysis, using the chi-square test for qualitative variables and the t test for quantitative variables. We then performed binary logistic regression to identify independent predictors of DOAC use in these populations and calculated their respective odds ratios (ORs).

The characteristics of the population are summarized in table 1. Compared with younger patients, the group of patients aged ≥80 years (n=376) comprised significantly more women (57.7% vs 41.5%, P<.001) and patients with heart failure (29.8% vs 20.2%, P<.001) or vascular disease (19.7 vs 12.8%, P=.003). Although the differences were not significant, older patients were also more likely to have a history of bleeding (5.9% vs 3.8%, P=.12) or stroke (9.3% vs 7.1%, P=.20).

Table 1.

Clinical and epidemiological characteristics of the study population by age

  Total (n=1039)  <80 y (n=663)  80 y (n=376)  P 
Hypertension  81.5  77.9  88  <.001 
Type 2 diabetes mellitus  26.3  25.7  26.7  .71 
History of cancer  6.6  6.5  6.9  .78 
Coronary artery disease  12.1  10.8  14.4  .08 
Anemia  16.3  12.5  23.2  <.001 
Permanent AF  50.5  42  66.5  <.001 
Prior AF  79.8  77.2  84.3  .006 
Sinus rhythm (consultation)  35  42.5  21.9  <.001 
CHA2DS2-VASc score  3.4±1.6  2.9±1.6  4.4±1.1  <.001 
HAS-BLED score (without labile INR)  1.2±0.8  1.1±0.8  1.4±0.7  <.001 
GFR, mL/min/1.73 m2  70.9±24.9  76.2±23.1  61.5±25  <.001 
Antiarrhythmic treatment  7.3  9.6  3.1  .005 
Beta-blockers  71.6  75.7  64.4  <.001 
Digoxin  18.8  15.1  25.3  <.001 
Aspirin (prior use)  10.2  10.4  9.8  .77 
P2Y12 receptor blockers (prior use)  2.3  2.9  .32 
Low-molecular-weight heparin (prior use)  3.4  3.3  3.5  .90 
DOACs  67.6  69.3  64.1  .08 
Low-dose DOACs  15.3  7.6  29.9  <.001 
DOAC underdosinga  10.5  6.4  18.5  <.001 
DOAC overdosingb  18.8  8.8  38  <.001 

AF, atrial fibrillation; DOACs, direct oral anticoagulants; GFR, glomerular filtration rate; INR, international normalized ratio.


Use of a lower than indicated dose according to summary of product characteristics.


Use of a normal dose in a patient with a n indication for low-dose DOAC therapy according to the summary of product characteristics.

Despite their less favorable profile, patients aged ≥80 years were more likely to be on AOCs (94.9% vs. 90% for those aged <80 years, P=.005). The difference for the prescription of DOACs, however, was not significant (64.1% v. 69.3%; P=.08), although a higher proportion of older patients were on low doses (29.9% vs 7.6%, P<.001). The only significant difference observed in terms of the use of specific DOACs was for dabigatran, which was prescribed less often to patients aged ≥80 years (figure 1).

Figure 1.

Differences in anticoagulant use according to age. DOACs, direct anticoagulants; OACs, oral anticoagulants; VKAs, vitamin K antagonists.


On multivariate analysis, an age ≥80 years was not associated with a lower use of DOACs (OR=1.16; 95% confidence interval [95%CI], 0.58-2.31; P<0.67). By contrast, both heart failure (OR=0.60; 95%CI, 0.40-0.90; P=.013) and chronic kidney failure (CKF) (OR=0.55; 95%CI, 0.41-0.76; P<.001) were independent predictors of lower DOAC use.

Generally speaking, there is sufficient evidence to recommend AOC therapy to elderly patients as it produces a net benefit in terms of a reduced risk of death, ischemic stroke, and intracranial hemorrhage (in this last case even in patients with a HAS-BLED score ≥3).3 There is also evidence that AOCs result in an absolute reduction of stroke risk in elderly patients and that the reduction in this population is even higher than in younger patients.4

One notable finding of our study was that over 90% of patients with NVAF were on AOC therapy, and there were no differences between patients aged <80 years and ≥80 years. This rate is even higher than that reported in a quality US clinical practice registry, where less than 80% of patients with NFAF were on AOCs and use was higher in younger patients.5

Appropriate choice of anticoagulant dose is necessary to ensure effective protection against stroke and to prevent an increased risk of bleeding. Subjective judgements based on age could erroneously lead to the prescription of low DOAC doses in elderly patients if other factors such as low body weight (<60kg) or CKF are not taken into account. It is noteworthy that underdosing (18.5%) and overdosing (38%) were common in our series, even though almost 35% of patients had a glomerular filtration rate <50mL/min, which is a criterion for using lower doses for certain DOACs. After adjusting for sex, bleeding risk, CKF, and prior bleeding, an age of ≥80 years was independently associated with a 3-fold increased odds of underdosing (OR=3.01; 95%CI, 1.83-4.92; P<.001). It was also associated with an increased odds of overdosing (OR=3.11, 95%CI, 1.66-5.84, P<.001), although the strongest independent predictor of overdosing, irrespective of age, was CKF, as 99% of these patients had a glomerular filtration rate <60mL/min.

In conclusion, our findings from a clinical AF registry indicate that DOAC use among elderly patients may be common, although the prognostic benefits of this treatment might be lower than expected, as we found that age ≥80 years was associated with both an inappropriate use of low doses and an excessive use of higher-than-indicated doses (primarily in patients with CKF).


This study was partially funded by an unconditional grant from Daiichi-Sankyo and Bayer.


We would like to thank Dr Ruiz Ortiz for revising this manuscript and providing helpful comments.

J.J. Gómez-Doblas, J. Muñiz, J.J. Alonso Martin, et al.
en representación de los colaboradores del estudio OFRECE. Prevalencia de fibrilación auricular en España. Resultados del estudio OFRECE.
Rev Esp Cardiol., 67 (2014), pp. 259-269
C.T. Ruff, R.P. Giugliano, E. Braunwald.
Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with auricular fibrillation: A meta-analysis of randomised trials.
Lancet., 383 (2014), pp. 955-962
L. Friberg, M. Rosenqvist, G.Y. Lip.
Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillation cohort study.
Circulation., 125 (2012), pp. 2298-2307
F. Andreotti, B. Rocca, S. Husted, Antithrombotic therapy in the elderly: expert position paper of the European Society of Cardiology Working Group on Thrombosis, et al.
Eur Heart J., 36 (2015), pp. 3238-3249
J.P. Piccini, H. Xu, M. Cox.
Adherence to guideline-directed stroke prevention therapy for atrial fibrillation is achievable — first results from Get With The Guidelines–Atrial Fibrillation (GWTG-AFIB).
Circulation., 139 (2019), pp. 1497-1506
Copyright © 2020. Sociedad Española de Cardiología
Revista Española de Cardiología (English Edition)

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