Mortality associated with the use of digoxin in the treatment of atrial fibrillation: an integrative review
DOI:
https://doi.org/10.33448/rsd-v10i4.14116Keywords:
Digoxin; Atrial fibrillation; Drug therapy.Abstract
Atrial fibrillation (AF) is the most prevalent arrhythmia, triggering an irregular and fast heart rhythm. Although it is not always the drug of first choice, digoxin is still widely used, although there is a fine line between its therapeutic effects, adverse effects, and mortality. Therefore, the aim of this study is to seek clinical evidence on the correlation between the use of digoxin and mortality in patients with AF. Thus, a literature search was conducted using the descriptors "(Digoxin) AND (Atrial fibrillation) AND (drug therapy)" in the PubMed, Virtual Health Library (VHL), Scientific Electronic Library Online (Scielo) and Cochrane databases. The search was conducted during the month of February 2021. After applying the defined inclusion criteria, 15 studies were selected. After analysis, it was evident the increasing number of studies that relate mortality to digoxin therapy in patients with AF and in association with comorbidities, such as heart failure (HF). Therefore, although there is no consensus, mortality was higher in groups of patients with AF, with or without cardioverter defibrillator, who used digoxin; mortality was even higher in the elderly, in patients with kidney disease, in patients with AF without HF and in the absence of therapeutic monitoring. Given the evidence presented in this review, we can state that the use of digoxin in patients with AF should be avoided or undertaken with caution and close monitoring.
References
Adedinsewo, D., Xu, J., Agasthi, P., Oderinde, A., Adekeye, O., Sachdeva, R., ... & Onwuanyi, A. (2017). Effect of digoxin use among Medicaid enrollees with atrial fibrillation. Circulation: Arrhythmia and Electrophysiology, 10(5), e004573.
Al-Zakwani, I., Panduranga, P., Zubaid, M., Sulaiman, K., Rashed, W. A., Alsheikh-Ali, A. A., ... & Amin, H. (2016). 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. Journal of cardiovascular pharmacology and therapeutics, 21(3), 273-279.
Benjamin, E. J., Muntner, P., Alonso, A., Bittencourt, M. S., Callaway, C. W., Carson, A. P., ... & American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. (2019). Heart disease and stroke statistics—2019 update: a report from the American Heart Association. Circulation, 139(10), e56-e528.
Biteker, M., Başaran, Ö., Dogan, V., Beton, O., Tekinalp, M., Çağrı Aykan, A., ... & Kırma, C. (2016). Real‐life use of digoxin in patients with non‐valvular atrial fibrillation: data from the RAMSES study. Journal of clinical pharmacy and therapeutics, 41(6), 711-717.
Chao, T. F., Liu, C. J., Tuan, T. C., Chen, S. J., Wang, K. L., Lin, Y. J., ... & Chen, S. A. (2015). Rate-control treatment and mortality in atrial fibrillation. Circulation, 132(17), 1604-1612.
Charfi, R., Sassi, M. B., Gaies, E., Jebabli, N., Daghfous, R., & Trabelsi, S. (2020). Digoxin Therapeutic Drug Monitoring: Age Influence and Adverse Events. La Tunisie medicale, 98(1), 35-40.
Charnigo, R., Khairy, P., Guo, J., Shohoudi, A., & Elayi, C. S. (2018). Use of digoxin in atrial fibrillation: One step further in the mortality controversy from the AFFIRM study. Pacing and Clinical Electrophysiology, 41(7), 713-719.
Chugh, S. S., Havmoeller, R., Narayanan, K., Singh, D., Rienstra, M., Benjamin, E. J., ... & Murray, C. J. (2014). Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation, 129(8), 837-847.
de Moraes, E. R. F. L., Cirenza, C., Lopes, R. D., Carvalho, A. C., Guimaraes, P. O., Rodrigues, A. A. E., & de Paola, A. A. V. (2019). Prevalence of atrial fibrillation and stroke risk assessment based on telemedicine screening tools in a primary healthcare setting. European journal of internal medicine, 67, 36-41.
Erath, J. W., Vamos, M., & Hohnloser, S. H. (2016). Effects of digitalis on mortality in a large cohort of implantable cardioverter defibrillator recipients: results of a long-term follow-up study in 1020 patients. European Heart Journal-Cardiovascular Pharmacotherapy, 2(3), 168-174.
Gao, Y., Chang, S., Du, X., Dong, J., Xu, X., Zhou, Y., ... & Ma, C. (2019). Association Between Digoxin Use and Adverse Outcomes Among Patients in the Chinese Atrial Fibrillation Registry. American Journal of Cardiovascular Drugs, 19(6), 579-587.
García-Iranzo, E. M., Rodríguez-Lucena, F. J., Matoses-Chirivella, C., García-Monsalve, A., Murcia-López, A. C., & Navarro-Ruiz, A. (2017). Pharmacokinetic monitoring of chronic treatment with digoxin from Primary Health Care. Farmacia hospitalaria: organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria, 41(4), 527-532.
Go, A. S., Hylek, E. M., Phillips, K. A., Chang, Y., Henault, L. E., Selby, J. V., & Singer, D. E. (2001). Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. Jama, 285(18), 2370-2375.
Goldberger, Z. D., & Alexander, G. C. (2014). Digitalis use in contemporary clinical practice: refitting the foxglove. JAMA internal medicine, 174(1), 151-154.
Gonzalez‐Loyola, F., Abellana, R., Verdú‐Rotellar, J. M., Bustamante Rangel, A., Clua‐Espuny, J. L., & Muñoz, M. A. (2018). Mortality in heart failure with atrial fibrillation: Role of digoxin and diuretics. European journal of clinical investigation, 48(11), e13014.
Hindricks, G., Potpara, T., Dagres, N., Arbelo, E., Bax, J. J., Blomström-Lundqvist, C., Boriani, G., Castella, M., Dan, G. A., Dilaveris, P. E., Fauchier, L., Filippatos, G., Kalman, J. M., La Meir, M., Lane, D. A., Lebeau, J. P., Lettino, M., Lip, G., Pinto, F. J., Thomas, G. N., … ESC Scientific Document Group (2020). 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). European heart journal, ehaa612. Advance online publication. https://doi.org/10.1093/eurheartj/ehaa612
January, C. T., Wann, L. S., Alpert, J. S., Calkins, H., Cigarroa, J. E., Cleveland, J. C., Jr, Conti, J. B., Ellinor, P. T., Ezekowitz, M. D., Field, M. E., Murray, K. T., Sacco, R. L., Stevenson, W. G., Tchou, P. J., Tracy, C. M., Yancy, C. W., & ACC/AHA Task Force Members (2014). 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation, 130(23), 2071–2104. https://doi.org/10.1161/CIR.0000000000000040
January, C. T., Wann, L. S., Calkins, H., Chen, L. Y., Cigarroa, J. E., Cleveland, J. C., ... & Yancy, C. W. (2019). 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. Journal of the American College of Cardiology, 74(1), 104-132.
Kornej, J., Börschel, C. S., Benjamin, E. J., & Schnabel, R. B. (2020). Epidemiology of atrial fibrillation in the 21st century: novel methods and new insights. Circulation Research, 127(1), 4-20.
Lopes, R. D., Rordorf, R., De Ferrari, G. M., Leonardi, S., Thomas, L., Wojdyla, D. M., ... & ARISTOTLE Committees and Investigators. (2018). Digoxin and mortality in patients with atrial fibrillation. Journal of the American College of Cardiology, 71(10), 1063-1074.
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & PRISMA Group (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS medicine, 6(7), e1000097. https://doi.org/10.1371/journal.pmed.1000097
Rahman, F., Kwan, G. F., & Benjamin, E. J. (2014). Global epidemiology of atrial fibrillation. Nature Reviews Cardiology, 11(11), 639.
Okin, P. M., Hille, D. A., Wachtell, K., Kjeldsen, S. E., Boman, K., Dahlöf, B., & Devereux, R. B. (2015). Digoxin use and risk of mortality in hypertensive patients with atrial fibrillation. Journal of hypertension, 33(7), 1480-1486.
Ren, Y., Ribas, H. T., Heath, K., Wu, S., Ren, J., Shriwas, P., ... & Kinghorn, A. D. (2020). Na+/K+-ATPase-Targeted Cytotoxicity of (+)-Digoxin and Several Semisynthetic Derivatives. Journal of natural products, 83(3), 638-648.
Somberg J. C. (2014). Digoxin therapy for atrial fibrillation in the twenty-first century. American journal of therapeutics, 21(5), 325–326. https://doi.org/10.1097/MJT.0000000000000153
Van Gelder, I. C., Rienstra, M., Crijns, H. J., & Olshansky, B. (2016). Rate control in atrial fibrillation. The Lancet, 388(10046), 818-828.
Souza, M. T. D., Silva, M. D. D., & Carvalho, R. D. (2010). Revisão integrativa: o que é e como fazer. Einstein (São Paulo), 8(1), 102-106.
Washam, J. B., Stevens, S. R., Lokhnygina, Y., Halperin, J. L., Breithardt, G., Singer, D. E., ... & Committee, R. A. S. (2015). 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). The Lancet, 385(9985), 2363-2370.
Yu, H. T., Yang, P. S., Lee, H., You, S. C., Kim, T. H., Uhm, J. S., ... & Joung, B. (2017). Outcomes of Rate-Control Treatment in Patients With Atrial Fibrillation and Heart Failure―A Nationwide Cohort Study―. Circulation Journal, CJ-17.
Zoni-Berisso, M., Lercari, F., Carazza, T., & Domenicucci, S. (2014). Epidemiology of atrial fibrillation: European perspective. Clinical epidemiology, 6, 213.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Katarina Venâncio Antunes Romeu Ramos; Vinícius Almeida da Nóbrega; Gabrielly Araújo Vilela; Giovanna Lima Figueiredo da Silva; Letícia Galvão Calafange de Carvalho; Ezymar Gomes Cayana; Saulo Rios Mariz
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.