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Current Cardiology Reviews

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ISSN (Print): 1573-403X
ISSN (Online): 1875-6557

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Review Article

Digoxin in Atrial Fibrillation: An Old Topic Revisited

Author(s): Filipe Ferrari, Igor R.M.F. Santander and Ricardo Stein*

Volume 16, Issue 2, 2020

Page: [141 - 146] Pages: 6

DOI: 10.2174/1573403X15666190618110941

Price: $65

Abstract

Digoxin has been used for more than 50 years in patients with Atrial Fibrillation (AF), with the goal of Controlling Heart Rate (HR) and restoring sinus rhythm. In the last two decades, several studies have correlated therapeutic use of digoxin with increased mortality. However, such studies have potential biases that cannot be disregarded, mainly because they are cross-sectional experiments or post-hoc analyses of Randomized Controlled Trials (RCTs). Despite uncertainties regarding the safety of digoxin in this setting, it remains one of the most prescribed drugs for AF worldwide. On the other hand, the absence of any RCTs designed to evaluate mortality makes a definitive conclusion more difficult to reach; therefore, this medication must be used with care. In this review, we explored the therapeutic use of digoxin in the context of AF, discussed mortality data by means of critical analysis in the light of the best available evidence, and position ourselves in relation to more rigorous control of serum levels of this drug in daily practice.

Keywords: Digoxin, serum level, toxicity, mortality, heart failure, chronic atrial fibrillation.

Graphical Abstract

[1]
Virgadamo S, Charnigo R, Darrat Y, Morales G, Elayi CS. Digoxin: A systematic review in atrial fibrillation, congestive heart failure and post myocardial infarction. World J Cardiol 2015; 7(11): 808-16.
[http://dx.doi.org/10.4330/wjc.v7.i11.808] [PMID: 26635929]
[2]
Tamargo J, Delpón E, Caballero R. The safety of digoxin as a pharmacological treatment of atrial fibrillation. Expert Opin Drug Saf 2006; 5(3): 453-67.
[http://dx.doi.org/10.1517/14740338.5.3.453] [PMID: 16610972]
[3]
Scalese MJ, Salvatore DJ. Role of digoxin in atrial fibrillation. J Pharm Pract 2017; 30(4): 434-40.
[http://dx.doi.org/10.1177/0897190016642361] [PMID: 27067743]
[4]
Hallberg P, Lindbäck J, Lindahl B, Stenestrand U, Melhus H. Digoxin and mortality in atrial fibrillation: a prospective cohort study. Eur J Clin Pharmacol 2007; 63(10): 959-71.
[http://dx.doi.org/10.1007/s00228-007-0346-9] [PMID: 17684738]
[5]
Pastori D, Farcomeni A, Bucci 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.
[http://dx.doi.org/10.1016/j.ijcard.2014.11.112] [PMID: 25460369]
[6]
Chao TF, Liu CJ, Chen SJ, et al. Does digoxin increase the risk of ischemic stroke and mortality in atrial fibrillation? A nationwide population-based cohort study. Can J Cardiol 2014; 30(10): 1190-5.
[http://dx.doi.org/10.1016/j.cjca.2014.05.009] [PMID: 25262860]
[7]
Wang ZQ, Zhang R, Chen MT, et al. Digoxin Is associated with increased all-cause mortality in patients with atrial fibrillation regardless of concomitant heart failure: A meta-analysis. J Cardiovasc Pharmacol 2015; 66(3): 270-5.
[http://dx.doi.org/10.1097/FJC.0000000000000274] [PMID: 26348825]
[8]
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.
[http://dx.doi.org/10.5603/CJ.a2016.0016] [PMID: 27064796]
[9]
Al-Zakwani I, Panduranga P, Zubaid M, et al. Impact of digoxin on mortality in patients with atrial fibrillation stratified by heart failure: Findings from gulf survey of atrial fibrillation events in the middle east. J Cardiovasc Pharmacol Ther 2016; 21(3): 273-9.
[http://dx.doi.org/10.1177/1074248415603505] [PMID: 26341119]
[10]
Gheorghiade M, Fonarow GC, van Veldhuisen DJ, 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.
[http://dx.doi.org/10.1093/eurheartj/eht120] [PMID: 23592708]
[11]
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.
[http://dx.doi.org/10.1136/hrt.2009.175786] [PMID: 19710030]
[12]
Rodríguez-Mañero M, Otero-Raviña F, García-Seara J, et al. Outcomes of a contemporary sample of patients with atrial fibrillation taking digoxin: results from the AFBAR study. Rev Esp Cardiol (Engl Ed) 2014; 67(11): 890-7.
[http://dx.doi.org/10.1016/j.rec.2014.01.014] [PMID: 25443813]
[13]
Lopes RD, Rordorf R, De Ferrari GM, et al. Digoxin and mortality in patients with atrial fibrillation. J Am Coll Cardiol 2018; 71(10): 1063-74.
[http://dx.doi.org/10.1016/j.jacc.2017.12.060] [PMID: 29519345]
[14]
Currie GM, Wheat JM, Kiat H. Pharmacokinetic considerations for digoxin in older people. Open Cardiovasc Med J 2011; 5: 130-5.
[http://dx.doi.org/10.2174/1874192401105010130] [PMID: 21769303]
[15]
Bauman JL, Didomenico RJ, Galanter WL. Mechanisms, manifestations, and management of digoxin toxicity in the modern era. Am J Cardiovasc Drugs 2006; 6(2): 77-86.
[http://dx.doi.org/10.2165/00129784-200606020-00002] [PMID: 16555861]
[16]
Bhatia SJ, Smith TW. Digitalis toxicity: mechanisms, diagnosis, and management. J Card Surg 1987; 2(4): 453-65.
[http://dx.doi.org/10.1111/j.1540-8191.1987.tb00204.x] [PMID: 2979993]
[17]
Rebagay WR, Caldwell RW. Different patterns of autonomic nerve activity produced by a polar vs. a neutral cardiac glycoside. J Pharmacol Exp Ther 1990; 253(1): 180-4.
[PMID: 2329504]
[18]
Watanabe AM. Digitalis and the autonomic nervous system. J Am Coll Cardiol 1985; 5(5)(Suppl. A): 35A-42A.
[http://dx.doi.org/10.1016/S0735-1097(85)80461-7] [PMID: 3886751]
[19]
Cheng JW, Rybak I. Use of digoxin for heart failure and atrial fibrillation in elderly patients. Am J Geriatr Pharmacother 2010; 8(5): 419-27.
[http://dx.doi.org/10.1016/j.amjopharm.2010.10.001] [PMID: 21335295]
[20]
Ehle M, Patel C, Giugliano RP. Digoxin: clinical highlights: a review of digoxin and its use in contemporary medicine. Crit Pathw Cardiol 2011; 10(2): 93-8.
[http://dx.doi.org/10.1097/HPC.0b013e318221e7dd] [PMID: 21988950]
[21]
Ziff OJ, Kotecha D. Digoxin: The good and the bad. Trends Cardiovasc Med 2016; 26(7): 585-95.
[http://dx.doi.org/10.1016/j.tcm.2016.03.011] [PMID: 27156593]
[22]
Greenblatt DJ, Duhme DW, Koch-Weser J. Pain and CPX elevation after intramuscular digoxin. N Engl J Med 1973; 288(13): 689.
[http://dx.doi.org/10.1056/NEJM197303292881317] [PMID: 4687265]
[23]
MacLeod-Glover N, Mink M, Yarema M, Chuang R. Digoxin toxicity: Case for retiring its use in elderly patients? Can Fam Physician 2016; 62(3): 223-8.
[PMID: 26975913]
[24]
Zeng WT, Liu ZH, Li ZY, Zhang M, Cheng YJ. Digoxin use and adverse outcomes in patients with atrial fibrillation. Medicine (Baltimore) 2016; 95(12): e2949
[http://dx.doi.org/10.1097/MD.0000000000002949] [PMID: 27015169]
[25]
Renard D, Rubli E, Voide N, Borruat FX, Rothuizen LE. Spectrum of digoxin-induced ocular toxicity: a case report and literature review. BMC Res Notes 2015; 8: 368.
[http://dx.doi.org/10.1186/s13104-015-1367-6] [PMID: 26298392]
[26]
Amjad W, Qureshi W, Farooq A, et al. Gastrointestinal side effects of antiarrhythmic medications: A review of current literature. Cureus 2017; 9(9): e1646
[http://dx.doi.org/10.7759/cureus.1646] [PMID: 29142794]
[27]
The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336(8): 525-33.
[http://dx.doi.org/10.1056/NEJM199702203360801] [PMID: 9036306]
[28]
Turakhia MP, Santangeli P, Winkelmayer WC, 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.
[http://dx.doi.org/10.1016/j.jacc.2014.03.060] [PMID: 25125296]
[29]
Allen LA, Fonarow GC, Simon DN, et al. Digoxin use and subsequent outcomes among patients in a contemporary atrial fibrillation cohort. J Am Coll Cardiol 2015; 65(25): 2691-8.
[http://dx.doi.org/10.1016/j.jacc.2015.04.045] [PMID: 26112191]
[30]
Whitbeck MG, Charnigo RJ, Khairy P, et al. Increased mortality among patients taking digoxin--analysis from the AFFIRM study. Eur Heart J 2013; 34(20): 1481-8.
[http://dx.doi.org/10.1093/eurheartj/ehs348] [PMID: 23186806]
[31]
Vamos M, Erath JW, Hohnloser SH. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. Eur Heart J 2015; 36(28): 1831-8.
[http://dx.doi.org/10.1093/eurheartj/ehv143] [PMID: 25939649]
[32]
Freeman JV, Reynolds K, Fang M, et al. Digoxin and risk of death in adults with atrial fibrillation: the ATRIA-CVRN study. Circ Arrhythm Electrophysiol 2015; 8(1): 49-58.
[http://dx.doi.org/10.1161/CIRCEP.114.002292] [PMID: 25414270]
[33]
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
[http://dx.doi.org/10.1371/journal.pone.0193924] [PMID: 29518134]
[34]
Vamos M, Erath JW, Benz AP, Lopes RD, Hohnloser SH. Meta-analysis of effects of digoxin on survival in patients with atrial fibrillation or heart failure: An update. Am J Cardiol 2019; 123(1): 69-74.
[http://dx.doi.org/10.1016/j.amjcard.2018.09.036] [PMID: 30539748]
[35]
Magalhães LP, Figueiredo MJO, Cintra FD, et al. II diretrizes brasileiras de fibrilação atrial. Arq Bras Cardiol 2016; 106(4)(Suppl. 2): 1-22.
[http://dx.doi.org/10.5935/abc.20160055] [PMID: 27487201]
[36]
Tariq S, Aronow WS. Use of inotropic agents in treatment of systolic heart failure. Int J Mol Sci 2015; 16(12): 29060-8.
[http://dx.doi.org/10.3390/ijms161226147] [PMID: 26690127]
[37]
Goldberger ZD, Alexander GC. Digitalis use in contemporary clinical practice: refitting the foxglove. JAMA Intern Med 2014; 174(1): 151-4.
[http://dx.doi.org/10.1001/jamainternmed.2013.10432] [PMID: 24217624]
[38]
Washam JB, Stevens SR, Lokhnygina Y, 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.
[http://dx.doi.org/10.1016/S0140-6736(14)61836-5] [PMID: 25749644]
[39]
Ahmed A, Gambassi G, Weaver MT, Young JB, Wehrmacher WH, Rich MW. Effects of discontinuation of digoxin vs. continuation at low serum digoxin concentrations in chronic heart failure. Am J Cardiol 2007; 100(2): 280-4.
[http://dx.doi.org/10.1016/j.amjcard.2007.02.099] [PMID: 17631083]
[40]
Pastori D, Carnevale R, Nocella C, et al. Digoxin and platelet activation in patients with atrial fibrillation: In vivo and in vitro study. J Am Heart Assoc 2018; 7(22): e009509
[http://dx.doi.org/10.1161/JAHA.118.009509] [PMID: 30571484]
[41]
Chan KE, Lazarus JM, Hakim RM. Digoxin associates with mortality in ESRD. J Am Soc Nephrol 2010; 21(9): 1550-9.
[http://dx.doi.org/10.1681/ASN.2009101047] [PMID: 20576808]
[42]
Papadakis MA, Wexman MP, Fraser C, Sedlacek SM. Hyperkalemia complicating digoxin toxicity in a patient with renal failure. Am J Kidney Dis 1985; 5(1): 64-6.
[http://dx.doi.org/10.1016/S0272-6386(85)80139-6] [PMID: 3966471]
[43]
Lindenfeld J, Albert NM, Boehmer JP, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010; 16(6)
[44]
January CT, Wann LS, Alpert JS, 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-e76.
[http://dx.doi.org/10.1016/j.jacc.2014.03.022] [PMID: 24685669]
[45]
Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37(38): 2893-962.
[http://dx.doi.org/10.1093/eurheartj/ehw210] [PMID: 27567408]
[46]
Rohde LEP, Montera MW, Bocchi EA, et al. Diretriz brasileira de insuficiência cardíaca crônica e aguda. Arq Bras Cardiol 2018; 111(3): 436-539.
[http://dx.doi.org/10.5935/abc.20180190] [PMID: 30379264]

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