Main Article Content

Sharmila Shamugam
Nur Syazwani Taridi
Adyani Md Redzuan


Atrial fibrillation, Digoxin, Pharmacokinetics


Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke and heart failure. Digoxin, a cardiac glycoside, has been a cornerstone in the management of AF for decades. This literature review explores the utilization of digoxin in atrial fibrillation, with a specific focus on its pharmacokinetic properties. Additionally, it discusses the challenges and concerns associated with digoxin's pharmacokinetics, including its narrow therapeutic window and the impact of patient-specific factors such as age, renal function, and drug interactions. This review highlights the importance of precise dosing and therapeutic drug monitoring to ensure both safety and efficacy in AF patients treated with digoxin. It also underscores the need for further research and clinical guidelines to optimize digoxin's use in the contemporary management of atrial fibrillation.

Abstract 459 | PDF Downloads 249


1. AH., M. Therapeutic Drug Monitoring. Appleton & Lange.1995;pp. 461-491 Digoxin. In S. GE (Ed.)
2. Allen, L. A., Fonarow, G. C., et al. Digoxin Use and Subsequent Outcomes Among Patients in a Contemporary Atrial Fibrillation Cohort. J Am Coll Cardiol.2015;65(25): 2691-2698 [ScienceDirect]
3. Association, A. A. P. Lexicomp Drug Information Handbook with International Trades Name Index. Wolters Kluwer Health,2014
4. Assurance, N. C. f. Q. The state of healthcare quality: reform, the quality agenda and resource use, 2010
5. AW, H. Monitoring drug therapy. Medicine 44, 2016:427-432
6. Chan, K. E., Lazarus, J. M., & Hakim, R. M. Digoxin associates with mortality in ESRD. J Am Soc Nephrol. 2010;21(9):1550-1559 [JASN]
7. Chao, T. F., Liu, C. J., Tuan, et al. Rate-control treatment and mortality in atrial fibrillation. Circulation. 2015; 132(17):1604-1612 [AHA]
8. Colilla, S., Crow, A., Petkun, et al. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013;112(8):1142-1147 [ScienceDirect]
9. Committee, C. P. W. Clinical Pharmacokinetics Pharmacy Handbook (Vol. 2nd). Pharmacy Practice & Development Division, 2019
10. DiDomenico, J. L. B. R. J., Viana, M., & Fitch, M. A Method of Determining the Dose of Digoxin for Heart Failure in the Modern Era. Arch Intern Med. 2006;16: 2539-2545
11. DiDomenico, R. J., Bress, A. P. et al.. Use of a simplified nomogram to individualize digoxin dosing versus standard dosing practices in patients with heart failure. Pharmacotherapy. 2014;34(11):1121-1131[accp]
12. Ferrari, F., Santander, I., & Stein, R. Digoxin in Atrial Fibrillation: An Old Topic Revisited. Curr Cardiol Rev. 2020;16(2):141-146
13. Freeman, J. V., Reynolds, K., Fang, et al.Digoxin and risk of death in adults with atrial fibrillation: the ATRIA-CVRN study. Circ Arrhythm Electrophysiol.2015;8(1): 49-58
14. Freestone, B., Rajaratnam, R., Hussain, N., & Lip, G. Y. Admissions with atrial fibrillation in a multiracial population in Kuala Lumpur, Malaysia. Int J Cardiol. 2003; 91(2-3):233-238 [ScienceDirect]
15. Friberg, L., Hammar, N., & Rosenqvist, M. Digoxin in atrial fibrillation: report from the Stockholm Cohort study of Atrial Fibrillation (SCAF). Heart. 2010;96(4):275-280
16. Hindricks, G., Potpara, T., Dagres, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42(5):373-498 [OXFORD]
17. Hirai, T., Kasai, Naganuma, et al. Population pharmacokinetic analysis and dosage recommendations for digoxin in Japanese patients with atrial fibrillation and heart failure using real-world data. BMC Pharmacol Toxicol. 2022;23(1):14 [SPRINGER NATURE]
18. Hirata S, I. S., Furukubo T, et al. Interactions between clarithromycin and digoxin in patients with end-stage renal disease. . Int J Clin Pharmacol Ther. 2005;43:30-36.
19. J E Doherty, W. H. P., M C Wilson. Studies With Tritiated Digoxin In Renal Failure. American Journal of Medicine, 1964:37
20. January, C. T., Wann, L. S., Calkins, H., et al. 2019 AHA/ACC/HRS Focused Update of the 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 Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019;140(2): e125-e151
21. Jessup M, A. W., Casey DE, et al. . (2009). ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the International Society for Heart and Lung Transplantation., 19(14), 1977-2016.
22. Juan Tamargo, E. D., Ricardo Caballero. The safety of digoxin as a pharmacological treatment of atrial fibrillation. Expert Opinion on Drug Safety. 2006;5(3):453-467
23. KF, A. Clinical benefits of low serum Digoxin concentrations in heart failure. Journal American College of Cardiology. 2002; 39(6):946-953
24. KF, A. Relationship of serum Digoxin concentration to mortality and morbidity in women in the Digitalis Investigation Group Trial: a retrospective analysis. Journal American College of Cardiology. 2005;46(3):497-504
25. Kirchhof, P., Benussi, Kotecha, Ahlsson et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-2962 [OXFORD]
26. KM., P. Deadly drug interactions in emergency medicine. Emerg Med Clin North Am.2004;22:845-863
27. Koh, K. T., Law, W. C., et al. Preliminary Results of Smartphone Electrocardiogram for Detecting Atrial Fibrillation After A Cerebral Ischemic Event: A Multi-center Randomised Controlled Trial. International Journal of Cardiology. 2019;297:1-2 [ScienceDirect]
28. Lang, R., Klein, H. O et al. Superiority of oral verapamil therapy to digoxin in treatment of chronic atrial fibrillation. Chest. 1983;83(3);491-499 [ScienceDirect]
29. Lopes, R. D., Rordorf, R., et al. Digoxin and Mortality in Patients With Atrial Fibrillation. J Am Coll Cardiol. 2018; 71(10):1063-1074 [ScienceDirect]
30. Malaysia, A. o. M. Clinical Practice Guidelines Atrial Fibrillation 2012 (N. H. A. o. Malaysia, Ed. 1st ed.) Ministry of Health malaysia, 2012
31. Mordasini MR, K. S., Schlienger RG. Appropriateness of digoxin level monitoring. . Swiss Med Wkly. 2002;132(35-36):506-12, 132(35-36):506-512
32. Mordasinia, M. R., , S. K., & , R. G. S. Appropriateness of digoxin level monitoring. EMH Swiss Medical Publishers Ltd. 2002;506-512
33. Parker RB, P. J., Johnson JA. Heart failure. In T. R. DiPiro JT, Yee GC, et al. (Ed.), Pharmacotherapy: A Pathophysiologic Approach (6th ed., pp. 219-260). McGraw-Hill; 2005:219-260
34. Peduzzi, P., Concato, J., Kemper, E., Holford, T.R. et al. A simulation study of the number of events per variable in logistic regression analysis. . Journal of Clinical Epidemiology. 1996;49(12): 1373–1379 [ScienceDirect]
35. Rang HP, D. M., Ritter JM, et al. Pharmacology. Churchill Livingstone, 1995
36. Rekha Garg, Thomas Smith, Salim Yusuf. The Effect Of Digoxin On Mortality And Morbidity In Patients With Heart Failure, 1997;336
37. Scalese, M. J., & Salvatore, D. J. Role of Digoxin in Atrial Fibrillation. Journal of Pharmacy Practice .2016;30(4):434-440
38. Shenasa, M., & Camm, A. J. Management of Atrial Fibrillation, 2014
39. Snow, V. e. a. Management of newly detected atrial fibrillation: a clinical practice guideline from American Academy of Family Physician and The American College of Physician. Annals Internal Medicine. 2003;139:1009-1017
40. Taggart, A. J., McDevitt, D. G., & Johnston, G. D. A Simple Aid To Digoxin Prescribing. European Journal of Pharmacology. 1987;33:441-445
41. Turakhia, Santangeli, Winkelmayer, 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):660-668 [ScienceDirect]
42. Vamos, M., Erath, & Hohnloser, S. H. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. European Heart Journal. 2015;36(28):1831-1838 [OXFORD]
43. Van Veldhuisen, Van Gelder, Ahmed, et al. Digoxin for patients with atrial fibrillation and heart failure: paradise lost or not? Eur Heart J. 2013;34(20):1468-1470 [OXFORD]
44. Wang, Zhang, Chen, et al. Digoxin Is Associated With Increased All-cause Mortality in Patients With Atrial Fibrillation Regardless of Concomitant Heart Failure: A Meta-analysis. Journal of Cardiovascular Pharmacology. 2015;66(3):6
45. Whitbeck, Charnigo, Khairy, et al.Increased mortality among patients taking digoxin--analysis from the AFFIRM study. Eur Heart J. 2013;34(20):1481-1488 [OXFORD]