Skip to main content
Top
Published in: Current Cardiology Reports 11/2018

01-11-2018 | Invasive Electrophysiology and Pacing (EK Heist, Section Editor)

Is There Still a Role for Digoxin in the Management of Atrial Fibrillation?

Authors: Jeffrey B. Washam, Manesh R. Patel

Published in: Current Cardiology Reports | Issue 11/2018

Login to get access

Abstract

Purpose of Review

A number of recent observational analyses have assessed clinical outcomes associated with digoxin use in patients with atrial fibrillation. In this review, we review these data and provide suggestions on the contemporary use of digoxin in patients with atrial fibrillation as supported by the recent evidence.

Recent Findings

Observational data from clinical trials and registries have provided variable results on the safety and efficacy of chronic digoxin use in patients with atrial fibrillation. In general, results have been consistent with an associated increase in adverse clinical outcomes with digoxin use in atrial fibrillation patients without heart failure. In atrial fibrillation patients with heart failure, while the weight of evidence suggested an associated risk with digoxin therapy, the results are inconsistent.

Summary

In patients with atrial fibrillation without heart failure, digoxin should generally be avoided. In atrial fibrillation patients with heart failure, digoxin should generally be reserved for patients that do not achieve adequate rate control or are not tolerant of other rate control therapies.
Literature
1.
go back to reference Digitalis Investigation G. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336(8):525–33.CrossRef Digitalis Investigation G. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336(8):525–33.CrossRef
2.
go back to reference January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1–76.CrossRefPubMedCentral January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1–76.CrossRefPubMedCentral
3.
go back to reference Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.CrossRef Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.CrossRef
4.
go back to reference Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.CrossRefPubMedCentral Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.CrossRefPubMedCentral
5.
go back to reference Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–104.CrossRefPubMedCentral Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–104.CrossRefPubMedCentral
6.
go back to reference Whitbeck MG, Charnigo RJ, Khairy P, Ziada K, Bailey AL, Zegarra MM, et al. Increased mortality among patients taking digoxin--analysis from the AFFIRM study. Eur Heart J. 2013;34(20):1481–8.CrossRefPubMedCentral Whitbeck MG, Charnigo RJ, Khairy P, Ziada K, Bailey AL, Zegarra MM, et al. Increased mortality among patients taking digoxin--analysis from the AFFIRM study. Eur Heart J. 2013;34(20):1481–8.CrossRefPubMedCentral
7.
go back to reference Gheorghiade M, Fonarow GC, van Veldhuisen DJ, Cleland JG, Butler J, Epstein AE, et al. Lack of evidence of increased mortality among patients with atrial fibrillation taking digoxin: findings from post hoc propensity-matched analysis of the AFFIRM trial. Eur Heart J. 2013;34(20):1489–97.CrossRefPubMedCentral Gheorghiade M, Fonarow GC, van Veldhuisen DJ, Cleland JG, Butler J, Epstein AE, et al. Lack of evidence of increased mortality among patients with atrial fibrillation taking digoxin: findings from post hoc propensity-matched analysis of the AFFIRM trial. Eur Heart J. 2013;34(20):1489–97.CrossRefPubMedCentral
8.
go back to reference Gjesdal K, Feyzi J, Olsson SB. Digitalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data. Heart. 2008;94(2):191–6.CrossRef Gjesdal K, Feyzi J, Olsson SB. Digitalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data. Heart. 2008;94(2):191–6.CrossRef
9.
go back to reference Washam JB, Stevens SR, Lokhnygina Y, Halperin JL, Breithardt G, Singer DE, et al. Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Lancet. 2015;385(9985):2363–70.CrossRefPubMedCentral Washam JB, Stevens SR, Lokhnygina Y, Halperin JL, Breithardt G, Singer DE, et al. Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Lancet. 2015;385(9985):2363–70.CrossRefPubMedCentral
10.
go back to reference Eisen A, Ruff CT, Braunwald E, Hamershock RA, Lewis BS, Hassager C et al. Digoxin use and subsequent clinical outcomes in patients with atrial fibrillation with or without heart failure in the ENGAGE AF-TIMI 48 Trial. J Am Heart Assoc. 2017;6(7). Eisen A, Ruff CT, Braunwald E, Hamershock RA, Lewis BS, Hassager C et al. Digoxin use and subsequent clinical outcomes in patients with atrial fibrillation with or without heart failure in the ENGAGE AF-TIMI 48 Trial. J Am Heart Assoc. 2017;6(7).
11.
go back to reference • Lopes RD, Rordorf R, De Ferrari GM, Leonardi S, Thomas L, Wojdyla DM, et al. Digoxin and mortality in patients with atrial fibrillation. J Am Coll Cardiol. 2018;71(10):1063–74. This analysis from the ARISTOTLE trial showed in atrial fibrillation patients taking digoxin, the risk of death was independently associated with serum digoxin concentrations. CrossRefPubMedCentral • Lopes RD, Rordorf R, De Ferrari GM, Leonardi S, Thomas L, Wojdyla DM, et al. Digoxin and mortality in patients with atrial fibrillation. J Am Coll Cardiol. 2018;71(10):1063–74. This analysis from the ARISTOTLE trial showed in atrial fibrillation patients taking digoxin, the risk of death was independently associated with serum digoxin concentrations. CrossRefPubMedCentral
12.
go back to reference Mulder BA, Van Veldhuisen DJ, Crijns HJ, Tijssen JG, Hillege HL, Alings M, et al. Digoxin in patients with permanent atrial fibrillation: data from the RACE II study. Heart Rhythm. 2014;11(9):1543–50.CrossRefPubMedCentral Mulder BA, Van Veldhuisen DJ, Crijns HJ, Tijssen JG, Hillege HL, Alings M, et al. Digoxin in patients with permanent atrial fibrillation: data from the RACE II study. Heart Rhythm. 2014;11(9):1543–50.CrossRefPubMedCentral
13.
go back to reference Hallberg P, Lindback J, Lindahl B, Stenestrand U, Melhus H, group R-H. Digoxin and mortality in atrial fibrillation: a prospective cohort study. Eur J Clin Pharmacol. 2007;63(10):959–71.CrossRefPubMedCentral Hallberg P, Lindback J, Lindahl B, Stenestrand U, Melhus H, group R-H. Digoxin and mortality in atrial fibrillation: a prospective cohort study. Eur J Clin Pharmacol. 2007;63(10):959–71.CrossRefPubMedCentral
14.
go back to reference Friberg L, Hammar N, Rosenqvist M. Digoxin in atrial fibrillation: report from the Stockholm Cohort study of Atrial Fibrillation (SCAF). Heart. 2010;96(4):275–80.CrossRefPubMedCentral Friberg L, Hammar N, Rosenqvist M. Digoxin in atrial fibrillation: report from the Stockholm Cohort study of Atrial Fibrillation (SCAF). Heart. 2010;96(4):275–80.CrossRefPubMedCentral
15.
go back to reference Chao TF, Liu CJ, Tuan TC, Chen SJ, Wang KL, Lin YJ, et al. Rate-control treatment and mortality in atrial fibrillation. Circulation. 2015;132(17):1604–12.CrossRefPubMedCentral Chao TF, Liu CJ, Tuan TC, Chen SJ, Wang KL, Lin YJ, et al. Rate-control treatment and mortality in atrial fibrillation. Circulation. 2015;132(17):1604–12.CrossRefPubMedCentral
16.
go back to reference • Turakhia MP, Santangeli P, Winkelmayer WC, Xu X, Ullal AJ, Than CT, et al. Increased mortality associated with digoxin in contemporary patients with atrial fibrillation: findings from the TREAT-AF study. J Am Coll Cardiol. 2014;64(7):660–8. This article represents one of the largest observational studies to date assessing digoxin use in patients with atrial fibrillation. CrossRefPubMedCentral • Turakhia MP, Santangeli P, Winkelmayer WC, Xu X, Ullal AJ, Than CT, et al. Increased mortality associated with digoxin in contemporary patients with atrial fibrillation: findings from the TREAT-AF study. J Am Coll Cardiol. 2014;64(7):660–8. This article represents one of the largest observational studies to date assessing digoxin use in patients with atrial fibrillation. CrossRefPubMedCentral
17.
go back to reference Freeman JV, Reynolds K, Fang M, Udaltsova N, Steimle A, Pomernacki NK, et al. Digoxin and risk of death in adults with atrial fibrillation: the ATRIA-CVRN study. Circ Arrhythm Electrophysiol. 2015;8(1):49–58.CrossRefPubMedCentral Freeman JV, Reynolds K, Fang M, Udaltsova N, Steimle A, Pomernacki NK, et al. Digoxin and risk of death in adults with atrial fibrillation: the ATRIA-CVRN study. Circ Arrhythm Electrophysiol. 2015;8(1):49–58.CrossRefPubMedCentral
18.
go back to reference Allen LA, Fonarow GC, Simon DN, Thomas LE, Marzec LN, Pokorney SD, et al. Digoxin use and subsequent outcomes among patients in a contemporary atrial fibrillation cohort. J Am Coll Cardiol. 2015;65(25):2691–8.CrossRefPubMedCentral Allen LA, Fonarow GC, Simon DN, Thomas LE, Marzec LN, Pokorney SD, et al. Digoxin use and subsequent outcomes among patients in a contemporary atrial fibrillation cohort. J Am Coll Cardiol. 2015;65(25):2691–8.CrossRefPubMedCentral
19.
go back to reference Pastori D, Farcomeni A, Bucci T, Cangemi R, Ciacci P, Vicario T, et al. Digoxin treatment is associated with increased total and cardiovascular mortality in anticoagulated patients with atrial fibrillation. Int J Cardiol. 2015;180:1–5.CrossRefPubMedCentral Pastori D, Farcomeni A, Bucci T, Cangemi R, Ciacci P, Vicario T, et al. Digoxin treatment is associated with increased total and cardiovascular mortality in anticoagulated patients with atrial fibrillation. Int J Cardiol. 2015;180:1–5.CrossRefPubMedCentral
20.
go back to reference Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study. Circulation. 2004;109(12):1509–13.CrossRefPubMedCentral Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study. Circulation. 2004;109(12):1509–13.CrossRefPubMedCentral
21.
go back to reference Hohnloser SH, Halperin JL, Camm AJ, Gao P, Radzik D, Connolly SJ, et al. Interaction between digoxin and dronedarone in the PALLAS trial. Circ Arrhythm Electrophysiol. 2014;7(6):1019–25.CrossRefPubMedCentral Hohnloser SH, Halperin JL, Camm AJ, Gao P, Radzik D, Connolly SJ, et al. Interaction between digoxin and dronedarone in the PALLAS trial. Circ Arrhythm Electrophysiol. 2014;7(6):1019–25.CrossRefPubMedCentral
22.
go back to reference Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003;289(7):871–8.CrossRefPubMedCentral Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003;289(7):871–8.CrossRefPubMedCentral
23.
go back to reference Qureshi W, O'Neal WT, Soliman EZ, Al-Mallah MH. Systematic review and meta-analysis of mortality and digoxin use in atrial fibrillation. Cardiol J. 2016;23(3):333–43.CrossRefPubMedCentral Qureshi W, O'Neal WT, Soliman EZ, Al-Mallah MH. Systematic review and meta-analysis of mortality and digoxin use in atrial fibrillation. Cardiol J. 2016;23(3):333–43.CrossRefPubMedCentral
24.
go back to reference Sethi NJ, Nielsen EE, Safi S, Feinberg J, Gluud C, Jakobsen JC. Digoxin for atrial fibrillation and atrial flutter: a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. PLoS One. 2018;13(3):e0193924.CrossRefPubMedCentral Sethi NJ, Nielsen EE, Safi S, Feinberg J, Gluud C, Jakobsen JC. Digoxin for atrial fibrillation and atrial flutter: a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. PLoS One. 2018;13(3):e0193924.CrossRefPubMedCentral
Metadata
Title
Is There Still a Role for Digoxin in the Management of Atrial Fibrillation?
Authors
Jeffrey B. Washam
Manesh R. Patel
Publication date
01-11-2018
Publisher
Springer US
Published in
Current Cardiology Reports / Issue 11/2018
Print ISSN: 1523-3782
Electronic ISSN: 1534-3170
DOI
https://doi.org/10.1007/s11886-018-1047-y

Other articles of this Issue 11/2018

Current Cardiology Reports 11/2018 Go to the issue

Interventional Cardiology (SR Bailey, Section Editor)

Update on Devices for Diastolic Dysfunction: Options for a No Option Condition?

Diabetes and Cardiovascular Disease (ND Wong, Section Editor)

Prevention of Heart Failure in Patients with Diabetes: Role of Diabetes Medications

Interventional Cardiology (SR Bailey, Section Editor)

Transcatheter Mitral Valve Therapy: Defining the Patient Who Will Benefit