Systematic Reviews
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Nov 26, 2015; 7(11): 808-816
Published online Nov 26, 2015. doi: 10.4330/wjc.v7.i11.808
Digoxin: A systematic review in atrial fibrillation, congestive heart failure and post myocardial infarction
Sebastiano Virgadamo, Richard Charnigo, Yousef Darrat, Gustavo Morales, Claude S Elayi
Sebastiano Virgadamo, Richard Charnigo, Yousef Darrat, Gustavo Morales, Claude S Elayi, Department of Cardiology, University of Kentucky Gill Heart Institute and Veterans Affairs Medical Center, Lexington, KY 40536, United States
Author contributions: Virgadamo S and Elayi CS designed the research; Virgadamo S performed the research; Charnigo R, Darrat Y and Morales G reviewed the data; Virgadamo S wrote the paper; Charnigo R edited the paper; Darrat Y, Morales G and Elayi CS supervised the paper; all authors approved the final manuscript.
Conflict-of-interest statement: All authors declare that they have no competing interests.
Data sharing statement: The table is available from the corresponding author at samy-claude.elayi@uky.edu.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Claude S Elayi, MD, Department of Cardiology, University of Kentucky Gill Heart Institute and Veterans Affairs Medical Center, 326 C.T. Wethington Bldg. 900 South Limestone Street, Lexington, KY 40536, United States. samy-claude.elayi@uky.edu
Telephone: +1-859-3235479 Fax: +1-859-3236475
Received: May 28, 2015
Peer-review started: June 1, 2015
First decision: July 3, 2015
Revised: August 21, 2015
Accepted: September 16, 2015
Article in press: September 18, 2015
Published online: November 26, 2015
Processing time: 186 Days and 3.1 Hours
Abstract

AIM: To review digoxin use in systolic congestive heart failure, atrial fibrillation, and after myocardial infarction.

METHODS: A comprehensive PubMed search was performed using the key words “digoxin and congestive heart failure”, “digoxin and atrial fibrillation”, “digoxin, atrial fibrillation and systolic congestive heart failure”, and “digoxin and myocardial infarction”. Only articles written in English were included in this study. We retained studies originating from randomized controlled trials, registries and included at least 500 patients. The studies included patients with atrial fibrillation or heart failure or myocardial infarction and had a significant proportion of patients (at least 5%) on digoxin. A table reviewing the different hazard ratios was developed based on the articles selected. Our primary endpoint was the overall mortality in the patients on digoxin vs those without digoxin, among patients with atrial fibrillation and also among patients with atrial fibrillation and systolic heart failure. We reviewed the most recent international guidelines to discuss current recommendations.

RESULTS: A total of 18 studies were found that evaluated digoxin and overall mortality in different clinical settings including systolic congestive heart failure and normal sinus rhythm (n = 5), atrial fibrillation with and without systolic congestive heart failure (n = 9), and myocardial infarction (n = 4). Overall, patients with systolic congestive heart failure with normal sinus rhythm, digoxin appears to have a neutral effect on mortality especially if close digoxin level monitoring is employed. However, most of the observational studies evaluating digoxin use in atrial fibrillation without systolic congestive heart failure showed an increase in overall mortality when taking digoxin. In the studies evaluated in this systematic review, the data among patients with atrial fibrillation and systolic congestive heart failure, as well as post myocardial infarction were more controversial. The extent to which discrepancies among studies are based on statistical methods is currently unclear, as these studies’ findings are generated by retrospective analyses that employed different techniques to address confounding.

CONCLUSION: Based on the potential risks and benefits, as well as the presence of alternative drugs, there is a limited role for digoxin in the management of patients with normal sinus rhythm and congestive heart failure. Based on the retrospective studies reviewed there is a growing volume of data showing increased mortality in those with only atrial fibrillation. The proper role of digoxin is, however, less certain in other subgroups of patients, such as those with both atrial fibrillation and systolic congestive heart failure or after a myocardial infarction. Further studies may provide helpful information for such subgroups of patients.

Keywords: Digoxin, Atrial fibrillation, Heart failure, Myocardial infarction, Mortality

Core tip: This systematic review evaluates mortality with the use of digoxin in congestive heart failure (CHF) with sinus rhythm, atrial fibrillation with and without CHF, and post myocardial infarction. In patients with CHF with sinus rhythm, there continues to be a niche for digoxin use as an adjunctive therapy for symptomatic control with the understanding that there is no effect on mortality. The role for digoxin among patients who only have atrial fibrillation seems very limited; however, those with atrial fibrillation and systolic congestive heart failure or post myocardial infarction need further assessment as many questions remain regarding the benefit of digoxin in this population.