Digoxin-associated mortality: A systematic review and meta-analysis of the literature

European Heart Journal

Volumn 36, Issue 28, 2015, Pages 1831-1838

  Vamos, Mate ^a   Erath, Julia W ^a   Hohnloser, Stefan H ^a  

^a GOETHE UNIVERSITY   (Germany)

Author keywords

Atrial fibrillation; Congestive heart failure; Digoxin; Mortality

Indexed keywords

DIGOXIN; ANTIARRHYTHMIC AGENT;

ARTICLE; ATRIAL FIBRILLATION; CONGESTIVE HEART FAILURE; DRUG INDICATION; DRUG USE; HUMAN; META ANALYSIS; MORTALITY; PRIORITY JOURNAL; RISK ASSESSMENT; SYSTEMATIC REVIEW; EPIDEMIOLOGY; HEART FAILURE;

ANTI-ARRHYTHMIA AGENTS; ATRIAL FIBRILLATION; DIGOXIN; EPIDEMIOLOGIC METHODS; HEART FAILURE; HUMANS;

EID: 84930630710     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehv143     Document Type: Article

References (46)

1. Uretsky BF, Young JB, Shahidi FE, Yellen LG, Harrison MC, Jolly MK. Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group. J Am Coll Cardiol 1993;22:955-962.
2. Packer M, Gheorghiade M, Young JB, Costantini PJ, Adams KF, Cody RJ, Smith LK, Van Voorhees L, Gourley LA, Jolly MK. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study. N Engl J Med 1993;329:1-7.
3. Garg R, Gorlin R, Smith T, Yusuf S, The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525-533.
4. Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, Love TE, Aronow WS, Adams KF Jr, Gheorghiade M. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation 2006;114:397-403.
5. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P, ESC Committee for Practice Guidelines. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Societyof Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012;14:803-869.
6. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P, ESC Committee for Practice Guidelines-CPG; Document Reviewers. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation - developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385-1413.
7. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL, American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147-e239.
8. Hallberg P, Lindbäck J, Lindahl B, Stenestrand U, Melhus H, RIKS-HIA group. Digoxin and mortality in atrial fibrillation: a prospective cohort study. Eur J Clin Pharmacol 2007;63:959-971.
9. Friberg L, Hammar N, Rosenqvist M. Digoxin in atrial fibrillation: report from the Stockholm Cohort study of Atrial Fibrillation (SCAF). Heart 2010;96:275-280.
10. Fauchier L, Grimard C, Pierre B, Nonin E, Gorin L, Rauzy B, Cosnay P, Babuty D, Charbonnier B. Comparison of beta blocker and digoxin alone and in combination for management of patients with atrial fibrillation and heart failure. Am J Cardiol 2009;103:248-254.
11. Dhaliwal AS, Bredikis A, Habib G, Carabello BA, Ramasubbu K, Bozkurt B. Digoxin and clinical outcomes in systolic heart failure patients on contemporary background heart failure therapy. Am J Cardiol 2008;102:1356-1360.
12. Butler J, Anand IS, Kuskowski MA, Rector T, Carson P, Cohn JN, Val-HeFT Investigators. Digoxin use and heart failure outcomes: results from the Valsartan Heart Failure Trial (Val-HeFT). Congest Heart Fail 2010;16:191-195.
13. Freeman JV, Yang J, Sung SH, Hlatky MA, Go AS. Effectiveness and safety of digoxin among contemporary adults with incident systolic heart failure. Circ Cardiovasc Qual Outcomes 2013;6:525-533.
14. Gjesdal K, Feyzi J, Olsson SB. Digitalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data. Heart 2008;94:191-196.
15. Whitbeck MG, Charnigo RJ, Khairy P, Ziada K, Bailey AL, Zegarra MM, Shah J, Morales G, Macaulay T, Sorrell VL, Campbell CL, Gurley J, Anaya P, Nasr H, Bai R, Di Biase L, Booth DC, Jondeau G, Natale A, Roy D, Smyth S, Moliterno DJ, Elayi CS. Increased mortality among patients taking digoxin - analysis from the AFFIRM study. Eur Heart J 2013;34:1481-1488.
16. Turakhia MP, Santangeli P, Winkelmayer WC, Xu X, Ullal AJ, Than CT, Schmitt S, Holmes TH, Frayne SM, Phibbs CS, Yang F, Hoang DD, Ho PM, Heidenreich PA. Increased mortality associated with digoxin in contemporary patients with atrial fibrillation: findings from the TREAT-AF study. J Am Coll Cardiol 2014;64:660-668.
17. Shah M, Avgil Tsadok M, Jackevicius CA, Essebag V, Behlouli H, Pilote L. Relation of digoxin use in atrial fibrillation and the risk of all-cause mortality in patients ≥65 years of age with versus without heart failure. Am J Cardiol 2014;114:401-406.
18. Gamst J, Christiansen CF, Rasmussen BS, Rasmussen LH, Thomsen RW. Pre-existing atrial fibrillation and risk of arterial thromboembolism and death following pneumonia: a population-based cohort study. BMJ Open 2014;4:e006486.
19. Chao TF, Liu CJ, Chen SJ, Wang KL, Lin YJ, Chang SL, Lo LW, Hu YF, Tuan TC, Chen TJ, Chiang CE, Chen SA. Does digoxin increase the risk of ischemic stroke and mortality in atrial fibrillation? A nationwide population-based cohort study. Can J Cardiol 2014;30:1190-1195.
20. Freeman JV, Reynolds K, Fang M, Udaltsova N, Steimle A, Pomernacki NK, Borowsky LH, Harrison TN, Singer DE, Go AS. Digoxin and risk of death in adults with atrial fibrillation: The ATRIA-CVRN Study. Circ Arrhythm Electrophysiol 2015;8:49-58.
21. Pastori D, Farcomeni A, Bucci T, Cangemi R, Ciacci P, Vicario T, Violi F, Pignatelli P. Digoxin treatment is associated with increased total and cardiovascular mortality in anticoagulated patients with atrial fibrillation. Int J Cardiol 2015;180:1-5.
22. Domanski M, Fleg J, Bristow M, Knox S. The effect of gender on outcome in digitalis-treated heart failure patients. J Card Fail 2005;11:83-86.
23. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700.
24. da Costa BR, Jüni P. Systematic reviews and meta-analyses of randomized trials: principles and pitfalls. Eur Heart J 2014;35:3336-3345.
25. Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg 2003;73:712-716.
26. Ghanbari H, Phard WS, Al-Ameri H, Latchamsetty R, Jongnarngsin K, Crawford T, Good E, Chugh A, Oral H, Bogun F, Morady F, Pelosi F Jr. Meta-analysis of safety and efficacy of uninterrupted warfarin compared to heparin-based bridging therapy during implantation of cardiac rhythm devices. Am J Cardiol 2012;110:1482-1488.
27. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539-1558.
28. Borenstein M, Hedges LV, Higgins JP, Rothstein H. A basic introduction to fixed and random effects models for meta-analysis. Res Synth Methods 2010;1:97-111.
29. st ed. Pondicherry/India: John Wiley & Sons, Ltd.; 2009.
30. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088-1101.
31. Gheorghiade M, Patel K, Filippatos G, Anker SD, van Veldhuisen DJ, Cleland JG, Metra M, Aban IB, Greene SJ, Adams KF, McMurray JJ, Ahmed A. Effect of oral digoxin in high-risk heart failure patients: a pre-specified subgroup analysis of the DIG trial. Eur J Heart Fail 2013;15:551-559.
32. Bourge RC, Fleg JL, Fonarow GC, Cleland JG, McMurray JJ, van Veldhuisen DJ, Gheorghiade M, Patel K, Aban IB, Allman RM, White-Williams C, White M, Filippatos GS, Anker SD, Ahmed A. Digoxin reduces 30-day all-cause hospital admission in older patients with chronic systolic heart failure. Am J Med 2013;126:701-708.
33. Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA 2003;289:871-878.
34. Rathore SS, Wang Y, Krumholz HM. Sex-based differences in the effect of digoxin for the treatment of heart failure. N Engl J Med 2002;347:1403-1411.
35. Gheorghiade M, Fonarow GC, van Veldhuisen DJ, Cleland JG, Butler J, Epstein AE, Patel K, Aban IB, Aronow WS, Anker SD, Ahmed A. 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;34:1489-1497.
36. Elayi CS, Whitbeck MG, Charnigo R, Shah J, Macaulay TE, Morales G, Gurley JC, Kakavand B, Thal S, Ching CK, Khaykin Y, Verma A, Barrett C, Bai R, Di Biase L, Patwardhan A, Moliterno DJ, Natale A, AFFIRM Study Investigators. Is there an association between external cardioversions and long-term mortality and morbidity? Insights from the Atrial Fibrillation Follow-up Investigation of Rhythm Management study. Circ Arrhythm Electrophysiol 2011;4:465-469.
37. Murphy SA. When 'digoxin use' is not the same as 'digoxin use': lessons from the AFFIRM trial. Eur Heart J 2013;34:1465-1467.
38. Rodríguez-Mañero M, Otero-Raviña F, García-Seara J, Zugaza-Gurruchaga L, Rodríguez-García JM, Blanco-Rodríguez R, Turrado Turrado V, Fernández-Villaverde JM, Vidal-Pérez RC, González-Juanatey JR, Barbanza Group Researchers. Outcomes of a Contemporary Sample of Patients With Atrial Fibrillation Taking Digoxin: Results From the AFBAR Study. Rev Esp Cardiol (Engl Ed) 2014;67:890-897.
39. Mulder BA, Van Veldhuisen DJ, Crijns HJ, Tijssen JG, Hillege HL, Alings M, Rienstra M, Van den Berg MP, Van Gelder IC, RACE II Investigators. Digoxin in patients with permanent atrial fibrillation: data from the RACE II study. Heart Rhythm 2014;11:1543-1550.
40. Opie LH. Digitalis, yesterday and today, but not forever. Circ Cardiovasc Qual Outcomes 2013;6:511-513.
41. Gheorghiade M, van Veldhuisen DJ, Colucci WS. Contemporary use of digoxin in the management of cardiovascular disorders. Circulation 2006;113:2556-2564.
42. Holmqvist F, Stridh M, Waktare JE, Sörnmo L, Olsson SB, Meurling CJ. Atrial fibrillatory rate and sinus rhythm maintenance in patients undergoing cardioversion of persistent atrial fibrillation. Eur Heart J 2006;27:2201-2207.
43. th ed. Philadelphia: Elsevier Saunders; 2014. p1001-1008.
44. Fromm MF, Kim RB, Stein M, Wilkinson GR, Roden DM. Inhibition of P-glycoprotein-mediated drug transport. A unifying mechanism to explain the interaction between digoxin and quinidine. Circulation 1999;99:552-557.
45. Hohnloser SH, Halperin JL, Camm AJ, Gao P, Radzik D, Connolly SJ. Interaction between digoxin and dronedarone in the PALLAS Trial. Circ Arrhythm Electrophysiol 2014;7:1019-1025.
46. Wyse DG. Death and digoxin: stop me if you've heard this one before. Can J Cardiol 2014;30:1145-1147.