Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data
Open accessAbstract
OBJECTIVE: To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods. DATA SOURCES AND STUDY SELECTION: Comprehensive literature search of Medline, Embase, the Cochrane Library, reference lists, and ongoing studies according to a prospectively registered design ( PROSPERO: CRD42014010783), including all studies published from 1960 to July 2014 that examined treatment with digoxin compared with control (placebo or no treatment). DATA EXTRACTION AND SYNTHESIS: Unadjusted and adjusted data pooled according to study design, analysis method, and risk of bias. MAIN OUTCOME MEASURES: Primary outcome (all cause mortality) and secondary outcomes (including admission to hospital) were meta-analysed with random effects modelling. RESULTS: 52 studies were systematically reviewed, comprising 621,845 patients. Digoxin users were 2.4 years older than control (weighted difference 95% confidence interval 1.3 to 3.6), with lower ejection fraction (33% v 42%), more diabetes, and greater use of diuretics and anti-arrhythmic drugs. Meta-analysis included 75 study analyses, with a combined total of 4,006,210 patient years of follow-up. Compared with control, the pooled risk ratio for death with digoxin was 1.76 in unadjusted analyses (1.57 to 1.97), 1.61 in adjusted analyses (1.31 to 1.97), 1.18 in propensity matched studies (1.09 to 1.26), and 0.99 in randomised controlled trials (0.93 to 1.05). Meta-regression confirmed that baseline differences between treatment groups had a significant impact on mortality associated with digoxin, including markers of heart failure severity such as use of diuretics (P=0.004). Studies with better methods and lower risk of bias were more likely to report a neutral association of digoxin with mortality (P<0.001). Across all study types, digoxin led to a small but significant reduction in all cause hospital admission (risk ratio 0.92, 0.89 to 0.95; P<0.001; n=29,525). CONCLUSIONS: Digoxin is associated with a neutral effect on mortality in randomised trials and a lower rate of admissions to hospital across all study types. Regardless of statistical analysis, prescription biases limit the value of observational data.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a meta-analysis of observational studies, digoxin had a neutral effect on mortality in patients with AF and concomitant heart failure (adjusted HR 0.90, 95% CI 0.70-1.16; propensity-matched RR 1.08, 95% CI 0.93-1.26).
“In a meta-analysis of observational studies, digoxin had a neutral effect on mortality in patients with AF and concomitant heart failure (adjusted observational studies HR 0.90, 95% CI 0.70-1.16;propensity-matched observational studies RR 1.08, 95% CI 0.93-1.26).”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [225]
Lower doses of digoxin (≤ 250 μg once daily), corresponding to serum digoxin levels of 0.5-0.9 ng/mL, may be associated with better prognosis.
“Lower doses of digoxin (≤ 250 µg once daily), corresponding to serum digoxin levels of 0.5-0.9ng/mL, may be associated with better prognosis.225”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [225]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & for the PRISMA Group (2009) · BMJ · doi:10.1136/bmj.b2535 · Cited by 83,823 · see citing works
Meta-analysis in clinical trials
DerSimonian, R., & Laird, N. (1986) · Controlled Clinical Trials · doi:10.1016/0197-2456(86)90046-2 · Cited by 39,552 · see citing works
Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & the PRISMA Group* (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-151-4-200908180-00135 · Cited by 37,554 · see citing works
The central role of the propensity score in observational studies for causal effects
ROSENBAUM, P. R., & RUBIN, D. B. (1983) · Biometrika · doi:10.1093/biomet/70.1.41 · Cited by 31,241 · see citing works
Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series
(2008) · doi:10.1002/9780470712184 · Cited by 25,048 · see citing works
McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O. D., et al. (2021) · PubMed · doi:10.1093/eurheartj/ehab670 · Cited by 19,618 · see citing works
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement
Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2009.06.005 · Cited by 19,575 · see citing works
Statistical Aspects of the Analysis of Data From Retrospective Studies of Disease
(1959) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/22.4.719 · Cited by 14,689 · see citing works
2013 ACCF/AHA Guideline for the Management of Heart Failure
Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Drazner, M. H., Fonarow, G. C., Geraci, S. A., Horwich, T., Januzzi, J. L., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.05.019 · Cited by 12,536 · see citing works
Austin, P. C. (2011) · Multivariate Behavioral Research · doi:10.1080/00273171.2011.568786 · Cited by 12,242 · see citing works
Ahmed, A., Jorna, T., & Bhandari, S. (2016) · The Nephron journals/Nephron journals · doi:10.1159/000447068 · Cited by 11,782 · see citing works
Causality: Models, Reasoning, and Inference
Pearl, J. (2009) · doi:10.1017/cbo9780511803161 · Cited by 11,653 · see citing works
The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure
Pitt, B., Zannad, F., Remme, W. J., Cody, R., Castaigne, A., Perez, A., Palensky, J., & Wittes, J. (1999) · New England Journal of Medicine · doi:10.1056/nejm199909023411001 · Cited by 9,214 · see citing works
2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation
January, C. T., Wann, L. S., Alpert, J. S., Calkins, H. G., Cigarroa, J. E., Cleveland, J. C., CONTI, J. B., Ellinor, P. T., Ezekowitz, M. D., Field, M. E., et al. (2014) · Circulation · doi:10.1161/cir.0000000000000041 · Cited by 7,119 · see citing works
ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012
Authors/Task Force Members, McMurray, J. J. V., Adamopoulos, S., Anker, S. D., Auricchio, A., Böhm, M., Dickstein, K., Falk, V., Filippatos, G., Fonseca, C., et al. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs104 · Cited by 6,879 · see citing works
Self-citationGuidelines for the management of atrial fibrillation
Authors/Task Force Members, Camm, A. J., Kirchhof, P. F., Lip, G. Y. H., Schotten, U., Savelieva, I., Ernst, S., Gelder, I. C. V., Al‐Attar, N., Hindricks, G., et al. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq278 · Cited by 5,875 · see citing works
Self-citationZhang, J., & Yu, K. F. (1998) · JAMA · doi:10.1001/jama.280.19.1690 · Cited by 4,138 · see citing works
Causal Diagrams for Epidemiologic Research
Greenland, S., Pearl, J., & Robins, J. M. (1999) · Epidemiology · doi:10.1097/00001648-199901000-00008 · Cited by 3,728 · see citing works
The Central Role of the Propensity Score in Observational Studies for Causal Effects
Rosenbaum, P. R., & Rubin, D. B. (1983) · Biometrika · doi:10.2307/2335942 · Cited by 3,495 · see citing works
Assessing Risk of Bias in Included Studies
Higgins, J. P., & Altman, D. G. (2008) · Cochrane Handbook for Systematic Reviews of Interventions · doi:10.1002/9780470712184.ch8 · Cited by 3,396 · see citing works
Eplerenone in patients with systolic heart failure and mild symptoms
Zannad, F., McMurray, J. J. V., Krum, H., van Veldhuisen, D. J., Swedberg, K., Shi, H., Vincent, J., Pocock, S. J., & Pitt, B. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1009492 · Cited by 3,111 · see citing works
Air Pollution and Hospital Admissions for Heart Disease in Eight U.S. Counties
Schwartz, J. D. (1999) · Epidemiology · doi:10.1097/00001648-199901000-00005 · Cited by 3,044 · see citing works
The effect of digoxin on mortality and morbidity in patients with heart failure
(1997) · New England Journal of Medicine · doi:10.1056/nejm199702203360801 · Cited by 3,016 · see citing works
Antlanger, M., Aschauer, S., Kopecky, C., Hecking, M., Kovarik, J. J., Werzowa, J. M., Mascherbauer, J., Genser, B., Säemann, M. D., & Bonderman, D. (2017) · Kidney & Blood Pressure Research · doi:10.1159/000473868 · Cited by 2,808 · see citing works
ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012
Authors/Task Force Members, McMurray, J. J. V., Adamopoulos, S., Anker, S. D., Auricchio, A., Böhm, M., Dickstein, K., Falk, V., Filippatos, G., Fonseca, C., et al. (2012) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfs105 · Cited by 2,644 · see citing works
Self-citationUsing Propensity Scores to Help Design Observational Studies: Application to the Tobacco Litigation
Rubin, D. B. (2001) · Health Services and Outcomes Research Methodology · doi:10.1023/a:1020363010465 · Cited by 2,228 · see citing works
Epidemiology and risk profile of heart failure
Bui, A. L., Horwich, T. B., & Fonarow, G. C. (2011) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2010.165 · Cited by 2,077 · see citing works
Lifetime Risk for Development of Atrial Fibrillation: The Framingham Heart Study
Lloyd-Jones, D. M., Wang, T. J., Leip, E. P., Larson, M. G., Levy, D., Vasan, R. S., D’Agostino, R. B., Massaro, J. M., Beiser, A., Wolf, P. A., et al. (2004) · Circulation · doi:10.1161/01.cir.0000140263.20897.42 · Cited by 2,041 · see citing works
Flather, M. D., Yusuf, S., Køber, L., Pfeffer, M. A., Hall, A. S., Murray, G. D., Torp-Pedersen, C. T., Ball, S. G., Pogue, J. M., Moyé, L. A., et al. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02212-1 · Cited by 1,580 · see citing works
Causality: Models, Reasoning, and Inference
Shanmugam, R. (2001) · Neurocomputing · doi:10.1016/s0925-2312(01)00330-7 · Cited by 1,377 · see citing works
Controlling the risk of spurious findings from meta-regression
Higgins, J. P. T., & Thompson, S. G. (2004) · Statistics in Medicine · doi:10.1002/sim.1752 · Cited by 1,267 · see citing works
Kim, S. Y., Park, J. E., Lee, Y. J., Seo, H.-J., Sheen, S.-S., Hahn, S., Jang, B.-H., & Son, H.-J. (2013) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2012.09.016 · Cited by 1,165 · see citing works
Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy
Maisel, W. H., & Stevenson, L. W. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)03373-8 · Cited by 967 · see citing works
Molyneux, A., Kerr, R. S. C., STRATTON, I. M., Sandercock, P., Clarke, M. J., Shrimpton, J. A., & Holman, R. R. (2002) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1053/jscd.2002.130390 · Cited by 957 · see citing works
Harbord, R. M., & Higgins, J. P. T. (2008) · The Stata Journal: Promoting communications on statistics and Stata · doi:10.1177/1536867x0800800403 · Cited by 897 · see citing works
Digoxin in Heart Failure with a Reduced Ejection Fraction: A Risk Factor or a Risk Marker?
Konstantinou, D. M., Karvounis, H. I., & Giannakoulas, G. A. (2016) · Cardiology · doi:10.1159/000444078 · Cited by 881 · see citing works
Association of Serum Digoxin Concentration and Outcomes in Patients With Heart Failure
Rathore, S. S., Curtis, J. P., Wang, Y., Bristow, M. R., & Krumholz, H. M. (2003) · JAMA · doi:10.1001/jama.289.7.871 · Cited by 772 · see citing works
Ahmed, A., Rich, M. W., Fleg, J. L., Zile, M. R., Young, J. B., Kitzman, D. W., Love, T. E., Aronow, W. S., Adams, K. F., & Gheorghiade, M. (2006) · Circulation · doi:10.1161/circulationaha.106.628347 · Cited by 605 · see citing works
Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK
Stewart, S., Murphy, N., Walker, A., McGuire, A., & McMurray, J. J. V. (2004) · Heart · doi:10.1136/hrt.2002.008748 · Cited by 590 · see citing works
Cohn, J. N. (1988) · JAMA · doi:10.1001/jama.1988.03720040031022 · Cited by 580 · see citing works
Kotecha, D., Holmes, J., Krum, H., Altman, D. G., Manzano, L., Cleland, J. G. F., Lip, G. Y. H., Coats, A. J. S., Andersson, B., Kirchhof, P., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61373-8 · Cited by 579 · see citing works
Self-citationDiBianco, R., Shabetai, R. W., Kostuk, W. J., Moran, J. F., Schlant, R. C., & Wright, R. (1989) · New England Journal of Medicine · doi:10.1056/nejm198903163201101 · Cited by 549 · see citing works
Goldstein, R. E., Boccuzzi, S. J., Cruess, D., & Nattel, S. (1991) · Circulation · doi:10.1161/01.cir.83.1.52 · Cited by 521 · see citing works
Terrin, N. C., Schmid, C. H., & Lau, J. (2005) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2005.01.006 · Cited by 493 · see citing works
Shrier, I., Boivin, J.-F., Steele, R. J., Platt, R. W., Furlan, A. D., Kakuma, R., Brophy, J. M., & Rossignol, M. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwm189 · Cited by 493 · see citing works
A definition of causal effect for epidemiological research
Hernán, M. Á. (2004) · Journal of Epidemiology & Community Health · doi:10.1136/jech.2002.006361 · Cited by 455 · see citing works
Ahmed, A., Rich, M. W., Love, T. E., Lloyd‐Jones, D. M., Aban, I., Colucci, W. S., Adams, K. F., & Gheorghiade, M. (2005) · European Heart Journal · doi:10.1093/eurheartj/ehi687 · Cited by 408 · see citing works
A Meta-Analysis of the Prognostic Significance of Atrial Fibrillation in Chronic Heart Failure
Mamas, M. A., Caldwell, J. C., Chacko, S., Garratt, C. J., Fath-Ordoubadi, F., & Neyses, L. (2009) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfp085 · Cited by 393 · see citing works
Pereira, C. A. D. B., & de Castilho, E. A. (2009) · American Journal of Epidemiology · doi:10.1093/aje/kwp016 · Cited by 374 · see citing works
Zakeri, R., Chamberlain, A. M., Roger, V. L., & Redfield, M. M. (2013) · Circulation · doi:10.1161/circulationaha.113.001475 · Cited by 370 · see citing works
Using Propensity Scores to Help Design Observational Studies: Application to the Tobacco Litigation
Rubin, D. B. (2006) · Cambridge University Press eBooks · doi:10.1017/cbo9780511810725.030 · Cited by 344 · see citing works
Chiang, C.-E., Naditch-Brûlé, L., Murin, J., Goethals, M., Inoue, H., O’Neill, J., Silva-Cardoso, J., Zharinov, O., Gamra, H., Alam, S., et al. (2012) · Circulation: Arrhythmia and Electrophysiology · doi:10.1161/circep.112.970749 · Cited by 327 · see citing works
Digoxin-associated mortality: a systematic review and meta-analysis of the literature
Vámos, M., Erath, J. W., & Hohnloser, S. H. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv143 · Cited by 302 · see citing works
Adams, K. F., Patterson, J. H., Gattis, W. A., O’Connor, C. M., Lee, C. R., Schwartz, T. A., & Gheorghiade, M. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.02.091 · Cited by 288 · see citing works
Increased mortality among patients taking digoxin—analysis from the AFFIRM study
Whitbeck, M. G., Charnigo, R. J., Khairy, P., Ziada, K., Bailey, A. L., Zegarra, M. M., Shah, J., Morales, G., Macaulay, T., Sorrell, V. L., et al. (2013) · European Heart Journal · doi:10.1093/eurheartj/ehs348 · Cited by 279 · see citing works
International Subarachnoid Aneurysm Trial of Neurosurgical Clipping Versus Endovascular Coiling
Ryttlefors, M., Enblad, P., Kerr, R. S. C., et al. (2008) · Stroke · doi:10.1161/strokeaha.107.506030 · Cited by 216 · see citing works
Digitalis-associated cardiac mortality after myocardial infarction.
Moss, A. J., Davis, H. T., Conard, D. L., et al. (1981) · Circulation · doi:10.1161/01.cir.64.6.1150 · Cited by 214 · see citing works
Increased Mortality Associated With Digoxin in Contemporary Patients With Atrial Fibrillation
Turakhia, M. P., Santangeli, P., Winkelmayer, W. C., Xu, X., Ullal, A. J., Than, C. T., Schmitt, S., Holmes, T. H., Frayne, S. M., Phibbs, C. S., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.03.060 · Cited by 208 · see citing works
Gheorghiade, M., Fonarow, G. C., van Veldhuisen, D. J., Cleland, J. G. F., Butler, J., Epstein, A. E., Patel, K., Aban, I. B., Aronow, W. S., Anker, S. D., et al. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht120 · Cited by 192 · see citing works
van Veldhuisen, D. J., Veld, A. J. M. I., Dunselman, P. H. J. M., Lok, D. J. A., Dohmen, H. J. M., Poortermans, J. C., Withagen, A. J. A. M., Pasteuning, W. H., Brouwer, J., & Lie, K. I. (1993) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(93)90579-p · Cited by 166 · see citing works
Washam, J. B., Stevens, S. R., Lokhnygina, Y. V., Halperin, J. L., BREITHARDT, G. E., Singer, D. E., Mahaffey, K. W., Hankey, G. J., Berkowitz, S. D., Nessel, C. C., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61836-5 · Cited by 145 · see citing works
Effect of digitalis treatment on survival after acute myocardial infarction
Bigger, J. T., Fleiss, J. L., Rolnitzky, L. M., Merab, J. P., & Ferrick, K. J. (1985) · The American Journal of Cardiology · doi:10.1016/0002-9149(85)90125-0 · Cited by 141 · see citing works
Ahmed, A., Pitt, B., Rahimtoola, S. H., Waagstein, F., White, M., Love, T. E., & D, E. B. M. (2007) · International Journal of Cardiology · doi:10.1016/j.ijcard.2006.12.001 · Cited by 119 · see citing works
Digoxin and mortality in atrial fibrillation: a prospective cohort study
Hallberg, P., Lindbäck, J., Lindahl, B., Stenestrand, U., Melhus, H., & for the RIKS-HIA group (2007) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-007-0346-9 · Cited by 113 · see citing works
Digoxin Associates with Mortality in ESRD
Chan, K. E., Lazarus, J. M., & Hakim, R. M. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2009101047 · Cited by 97 · see citing works
Digoxin Use and Subsequent Outcomes Among Patients in a Contemporary Atrial Fibrillation Cohort
Allen, L. A., Fonarow, G. C., Simon, D. N., Thomas, L. E., Marzec, L., Pokorney, S. D., Gersh, B. J., Go, A. S., Hylek, E. M., Kowey, P. R., et al. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.04.045 · Cited by 94 · see citing works
Digoxin Therapy and Mortality after Myocardial Infarction
Muller, J. E., Turi, Z. G., Stone, P. H., et al. (1986) · New England Journal of Medicine · doi:10.1056/nejm198601303140501 · Cited by 94 · see citing works
Ryan, T. J., Bailey, K. R., McCabe, C. H., et al. (1983) · Circulation · doi:10.1161/01.cir.67.4.735 · Cited by 91 · see citing works
Digoxin and Risk of Death in Adults With Atrial Fibrillation
Freeman, J. V., Reynolds, K., Fang, M. C., Udaltsova, N. V., Steimle, A. E., Pomernacki, N. K., Borowsky, L. H., Harrison, T. N., Singer, D. E., & Go, A. S. (2014) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.114.002292 · Cited by 82 · see citing works
Effectiveness and Safety of Digoxin Among Contemporary Adults With Incident Systolic Heart Failure
Freeman, J. V., Yang, J., Sung, S. H., Hlatky, M. A., & Go, A. S. (2013) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.111.000079 · Cited by 79 · see citing works
Fauchier, L., Grimard, C., Pierre, B., Nonin, E., Gorin, L., Rauzy, B., Cosnay, P., Babuty, D., & Charbonnier, B. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.09.064 · Cited by 77 · see citing works
Interaction Between Digoxin and Dronedarone in the PALLAS Trial
Hohnloser, S. H., Halperin, J. L., Camm, A. J., Gao, P., Radzik, D., & Connolly, S. J. (2014) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.114.002046 · Cited by 77 · see citing works
Calcium channel blockers in heart failure
Elkayam, U. (1998) · Cardiology · doi:10.1159/000047278 · Cited by 69 · see citing works
Hood, W. B., Dans, A. L., Guyatt, G. H., Jaeschke, R., & McMurray, J. J. V. (2004) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2003.12.005 · Cited by 69 · see citing works
Digoxin in patients with permanent atrial fibrillation: Data from the RACE II study
Mulder, B. A., van Veldhuisen, D. J., Crijns, H. J. G. M., Tijssen, J. G. P., Hillege, H. L., Alings, M., Rienstra, M., van den Berg, M. P., & Gelder, I. C. V. (2014) · Heart Rhythm · doi:10.1016/j.hrthm.2014.06.007 · Cited by 69 · see citing works
Digoxin Use and Digoxin Toxicity in the Post-DIG Trial Era
Hussain, Z., Swindle, J. P., & Hauptman, P. J. (2006) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2006.02.005 · Cited by 68 · see citing works
Shah, M., Tsadok, M. A., Jackevicius, C. A., Essebag, V., Behlouli, H., & Pilote, L. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2014.05.013 · Cited by 66 · see citing works
Digitalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data
Gjesdal, K., Feyzi, J. M., & Olsson, S. B. (2007) · Heart · doi:10.1136/hrt.2006.108399 · Cited by 65 · see citing works
Digoxin in atrial fibrillation: report from the Stockholm Cohort study of Atrial Fibrillation (SCAF)
Friberg, L., Hammar, N., & Rosenqvist, M. (2009) · Heart · doi:10.1136/hrt.2009.175786 · Cited by 63 · see citing works
Ahmed, A., Bourge, R. C., Fonarow, G. C., Patel, K., Morgan, C. J., Fleg, J. L., Aban, I., Love, T. E., Yancy, C. W., DEEDWANIA, P. C., et al. (2013) · The American Journal of Medicine · doi:10.1016/j.amjmed.2013.08.027 · Cited by 63 · see citing works
Bourge, R. C., Fleg, J. L., Fonarow, G. C., Cleland, J. G. F., McMurray, J. J. V., van Veldhuisen, D. J., Gheorghiade, M., Patel, K., Aban, I., Allman, R. M., et al. (2013) · The American Journal of Medicine · doi:10.1016/j.amjmed.2013.02.001 · Cited by 63 · see citing works
Ahmed, A. (2007) · The Journals of Gerontology Series A · doi:10.1093/gerona/62.3.323 · Cited by 59 · see citing works
Georgiopoulou, V. V., Kalogeropoulos, A. P., Giamouzis, G., Agha, S. A., Rashad, M. A., Waheed, S., Laskar, S. R., Smith, A. L., & Butler, J. (2009) · Circulation Heart Failure · doi:10.1161/circheartfailure.108.807032 · Cited by 59 · see citing works
Prognostic Importance of Digitalis After Acute Myocardial Infarction
Madsen, E. B., Gilpin, E. A., Henning, H., et al. (1984) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(84)80243-0 · Cited by 58 · see citing works
Calcium channel blockers in heart failure
Elkayam, U., Shotan, A., Mehra, A., & Ostrzega, E. (1993) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(93)90478-j · Cited by 58 · see citing works
Kitzman, D. W., Young, J. B., Rich, M. W., Adams, K. F., Zile, M. R., Aronow, W. S., Fleg, J. L., Love, T. E., Ahmed, A., & Gheorghiade, M. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/w1mr-sk27 · Cited by 58 · see citing works
Ward, R. E., Gheorghiade, M., Young, J. B., & Uretsky, B. F. (1995) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)00140-u · Cited by 57 · see citing works
Byington, R. P., & Goldstein, S. (1985) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(85)80297-7 · Cited by 55 · see citing works
Digoxin Use and Heart Failure Outcomes: Results from the Valsartan Heart Failure Trial (Val‐HeFT)
Butler, J., Anand, I. S., Kuskowski, M. A., Rector, T. S., Carson, P. E., Cohn, J. N., & for the Val‐HeFT Investigators (2010) · Congestive Heart Failure · doi:10.1111/j.1751-7133.2010.00161.x · Cited by 50 · see citing works
Declining public health burden of digoxin toxicity from 1991 to 2004
Haynes, K., Heitjan, D., Kanetsky, P., & Hennessy, S. (2008) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100458 · Cited by 49 · see citing works
The Effect of Gender on Outcome in Digitalis-Treated Heart Failure Patients
Domański, M., Fleg, J. L., Bristow, M. R., & Knox, S. (2005) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2004.07.002 · Cited by 47 · see citing works
Chao, T., Liu, C., Chen, S., Wang, K.-L., Lin, Y., Chang, S., Lo, L., Hu, Y., Tuan, T., Chen, T., et al. (2014) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2014.05.009 · Cited by 45 · see citing works
Exercise capacity and quality of life in the treatment of heart failure
Blackwood, R., Mayou, R., Garnham, J. C., et al. (1990) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1990.156 · Cited by 42 · see citing works
Chrome congestive heart failure
Køber, L., Torp-Pedersen, C. T., Gadsbøll, N., et al. (1994) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a060507 · Cited by 40 · see citing works
Digoxin in patients with atrial fibrillation and heart failure: A meta-analysis
Bavishi, C., Khan, A. R., & Ather, S. (2015) · International Journal of Cardiology · doi:10.1016/j.ijcard.2015.04.031 · Cited by 39 · see citing works
Pastori, D., Farcomeni, A., Bucci, T., Cangemi, R., Ciacci, P., Vicario, T., Violi, F., & Pignatelli, P. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.11.112 · Cited by 38 · see citing works
Ahmed, A., Aban, I., Weaver, M. T., Aronow, W. S., & Fleg, J. L. (2005) · European Journal of Heart Failure · doi:10.1016/j.ejheart.2005.10.002 · Cited by 34 · see citing works
When 'digoxin use' is not the same as 'digoxin use': lessons from the AFFIRM trial
Murphy, S. A. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht087 · Cited by 34 · see citing works
Patel, N., Hoosien, M., Deshmukh, A. J., Badheka, A. O., Grover, P. M., Shah, N. N., Singh, V., Mehta, K. D., Chothani, A., Savani, G. T., et al. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.10.040 · Cited by 31 · see citing works
Digitalis Use in Contemporary Clinical Practice
Goldberger, Z. D., & Alexander, G. C. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.10432 · Cited by 29 · see citing works
Dhaliwal, A. S., Brėdikis, A. J., Habib, G. B., Carabello, B. A., Ramasubbu, K., & Bozkurt, B. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.07.014 · Cited by 29 · see citing works
Eichhorn, E. J., Lukas, M. A., Wu, B., & Shusterman, N. H. (2000) · The American Journal of Cardiology · doi:10.1016/s0002-9149(00)01146-2 · Cited by 28 · see citing works
Individual patient data meta-analysis of beta-blockers in heart failure: rationale and design
Beta-Blockers in Heart Failure Collaborative Group, Kotecha, D., Manzano, L., Altman, D. G., Krum, H., Erdem, G., Williams, N., & Flather, M. D. (2013) · Systematic Reviews · doi:10.1186/2046-4053-2-7 · Cited by 28 · see citing works
Self-citationAndrey, J. L., Romero, S., García-Egido, A., Escobar, M. A., Corzo, R., Garcia-Dominguez, G., Lechuga, V., & Gómez, F. (2011) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2011.02771.x · Cited by 27 · see citing works
Observational cohort study of the safety of digoxin use in women with heart failure
Flory, J. H., Ky, B., Haynes, K., M Brunelli, S., Munson, J., Rowan, C., Strom, B. L., & Hennessy, S. (2012) · BMJ Open · doi:10.1136/bmjopen-2012-000888 · Cited by 27 · see citing works
Hashim, T., Elbaz, S., Patel, K., Morgan, C. J., Fonarow, G. C., Fleg, J. L., McGwin, G., Cutter, G., Allman, R. M., Prabhu, S. D., et al. (2013) · The American Journal of Medicine · doi:10.1016/j.amjmed.2013.08.006 · Cited by 27 · see citing works
Meyer, P., White, M., Mujib, M. U., Nozza, A., Love, T. E., Aban, I., Young, J. B., Wehrmacher, W. H., & Ahmed, A. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.05.068 · Cited by 26 · see citing works
A cohort study of digoxin exposure and mortality in men with prostate cancer
Flahavan, E. M., Sharp, L., Bennett, K., & Barron, T. I. (2013) · British Journal of Urology · doi:10.1111/bju.12287 · Cited by 25 · see citing works
Prophylaxis against respiratory syncytial virus in premature infants
Bont, L., van Vught, A., & Kimpen, J. (1999) · The Lancet · doi:10.1016/s0140-6736(99)02368-5 · Cited by 23 · see citing works
Digoxin and mortality in chronic heart failure
Lindsay, S. J., Kearney, M. T., Prescott, R. J., Fox, K. A. A., & Nolan, J. (1999) · The Lancet · doi:10.1016/s0140-6736(99)03815-5 · Cited by 20 · see citing works
Leor, J., Goldbourt, U., Behar, S., et al. (1995) · Cardiovascular Drugs and Therapy · doi:10.1007/bf00878094 · Cited by 20 · see citing works
Gamst, J., Christiansen, C. F., Rasmussen, B. S., Rasmussen, L. H., & Thomsen, R. W. (2014) · BMJ Open · doi:10.1136/bmjopen-2014-006486 · Cited by 20 · see citing works
Rodríguez‐Mañero, M., Otero-Raviña, F., García‐Seara, J., Zugaza-Gurruchaga, L., Rodríguez-García, J. M., Blanco-Rodríguez, R., Turrado, V. T., Fernández-Villaverde, J. M., Vidal-Pérez, R., & González‐Juanatey, J. R. (2014) · Revista Española de Cardiología · doi:10.1016/j.recesp.2014.01.015 · Cited by 18 · see citing works
The mortality risk associated with digitalis treatment after myocardial infarction
Moss, A. J., Bigger, J. T., Carleen, E., et al. (1987) · Cardiovascular Drugs and Therapy · doi:10.1007/bf02125465 · Cited by 17 · see citing works
Digoxin use and risk of mortality in hypertensive patients with atrial fibrillation
Okin, P. M., Hille, D. A., Wachtell, K., Kjeldsen, S. E., Boman, K., Dahlöf, B., & Devereux, R. B. (2015) · Journal of Hypertension · doi:10.1097/hjh.0000000000000559 · Cited by 16 · see citing works
Rodríguez‐Mañero, M., Otero-Raviña, F., García‐Seara, J., Zugaza-Gurruchaga, L., Rodríguez-García, J. M., Blanco-Rodríguez, R., Turrado, V. T., Fernández-Villaverde, J. M., Vidal-Pérez, R., & González‐Juanatey, J. R. (2014) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2014.01.014 · Cited by 16 · see citing works
Digoxin in advanced heart failure patients: A question of rhythm
Jorge, E., Baptista, R., Martins, H., et al. (2013) · Revista Portuguesa de Cardiologia · doi:10.1016/j.repc.2012.11.007 · Cited by 15 · see citing works
DIGOXIN AND RISK OF DEATH IN ADULTS WITH ATRIAL FIBRILLATION: THE ATRIA-CVRN STUDY
Freeman, J. V., Reynolds, K., Fang, M. C., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(13)60262-4 · Cited by 14 · see citing works
Does CMV infection play a role in myocarditis? New aspects from in-situ hybridization
Schönian, U., Crombach, M., & Maisch, B. (1991) · European Heart Journal · doi:10.1093/eurheartj/12.suppl_d.65 · Cited by 14 · see citing works
Adams, K. F., Patterson, J. H., & Gattis, W. A. (2005) · ACC Current Journal Review · doi:10.1016/j.accreview.2005.10.061 · Cited by 14 · see citing works
Digitoxin-associated mortality in acute myocardial infarction
Mølstad, P., & Abdelnoor, M. (1991) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a059827 · Cited by 13 · see citing works
García-Rubira, J. C., Calvo-Taracido, M., Francisco-Aparicio, F., et al. (2013) · Internal and Emergency Medicine · doi:10.1007/s11739-013-1032-9 · Cited by 12 · see citing works
Casiglia, E., Tikhonoff, V., PIZZIOL, A., et al. (1998) · Japanese Heart Journal · doi:10.1536/ihj.39.639 · Cited by 10 · see citing works
Eisenstein, E. L., Yusuf, S., Bindal, V., Bourassa, M. G., Horney, A., Collins, J. F., & Mark, D. B. (2006) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2006.04.002 · Cited by 10 · see citing works
Are coronary patients at higher risk with digoxin therapy? An ongoing controversy
Reicher-Reiss, H., Jonas, M., Boyko, V., et al. (1999) · International Journal of Cardiology · doi:10.1016/s0167-5273(98)00364-7 · Cited by 7 · see citing works
Ghali, J. K., Dunselman, P., Waagstein, F., Goldstein, S., Gottlieb, S. S., DEEDWANIA, P. C., & Wikstrand, J. (2004) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2004.02.008 · Cited by 7 · see citing works
Effect of digitalis treatment on survival after acute myocardial infarction
(1985) · The American Journal of Cardiology · doi:10.1016/0002-9149(85)90137-7 · Cited by 6 · see citing works
Digoxin therapy and survival in heart failure in sinus rhythm
Banerjee, A. K., & Campbell, R. W. F. (1996) · International Journal of Cardiology · doi:10.1016/0167-5273(96)02580-6 · Cited by 4 · see citing works
Cheitlin, M. D. (2010) · Yearbook of Cardiology · doi:10.1016/s0145-4145(09)79632-7 · Cited by 2 · see citing works
Digoxin in advanced heart failure patients: A question of rhythm
Jorge, E., Baptista, R., Martins, H., et al. (2013) · Revista Portuguesa de Cardiologia (English Edition) · doi:10.1016/j.repce.2012.11.020 · Cited by 1 · see citing works
Digoxin therapy and survival in heart failure in sinus rhythm
Banerjee, A. (1997) · International Journal of Cardiology · doi:10.1016/s0167-5273(96)02580-6 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab368 · Cited by 13,344 · see citing works
Self-citation2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure
Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G. F., Coats, A. J. S., Falk, V., González-Juanatey, J. R., Harjola, V.-P., Jankowska, E. A., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw128 · Cited by 11,429 · see citing works
Self-citation2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw210 · Cited by 6,418 · see citing works
Self-citation2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure
Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G. F., Coats, A. J. S., Falk, V., González-Juanatey, J. R., Harjola, V.-P., Jankowska, E. A., et al. (2016) · European Journal of Heart Failure · doi:10.1002/ejhf.592 · Cited by 5,866 · see citing works
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezw313 · Cited by 1,403 · see citing works
Self-citationHuang, Y., Cai, X., Mai, W., Li, M., & Hu, Y. (2016) · BMJ · doi:10.1136/bmj.i5953 · Cited by 1,012 · see citing works
2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation
Joglar, J. A., Chung, M. K., Armbruster, A. L., Benjamin, E. J., Chyou, J. Y., Cronin, E. M., Deswal, A., Eckhardt, L. L., Goldberger, Z. D., Gopinathannair, R., et al. (2024) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.08.017 · Cited by 933 · see citing works
McMurray, J. J. V., DeMets, D. L., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Langkilde, A. M., Martinez, F. A., Bengtsson, O., Ponikowski, P., Sabatine, M. S., et al. (2019) · European Journal of Heart Failure · doi:10.1002/ejhf.1548 · Cited by 222 · see citing works
Clinical Use of Digitalis: A State of the Art Review
Whayne, T. F. (2018) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-018-0292-1 · Cited by 99 · see citing works
Toews, I., Anglemyer, A., Nyirenda, J. L., Alsaid, D., Balduzzi, S., Grummich, K., Schwingshackl, L., & Bero, L. (2024) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.mr000034.pub3 · Cited by 60 · see citing works
Abdul-Rahim, A. H., MacIsaac, R. L., Jhund, P. S., Petrie, M. C., Lees, K. R., & McMurray, J. J. V. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.02.074 · Cited by 29 · see citing works
- Authors
- Ziff, O. J., Lane, D. A., Samra, M., Griffith, M., Kirchhof, P., Lip, G. Y. H., Steeds, R. P., Townend, J., & Kotecha, D.
- Affiliations
- Royal Free London NHS Foundation Trust (GB)
- Sandwell & West Birmingham Hospitals NHS Trust (GB)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Corresponding author
- Kotecha, Dipak
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2015-08-30
- Volume
- 351
- Pages
- h4451
- ISSN
- 1756-1833 (ISSN-L)
- PMC
- PMC4553205
- OpenAlex
- W2160601239
- Cited by
- 341
- References
- 134
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 29 · 2023: 35 · 2022: 28 · 2021: 40 · 2020: 35 · 2019: 27 · 2018: 33 · 2017: 34 · 2016: 31 · 2015: 9
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-09-15)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- BMJ (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (acceptedVersion, cc-by-nc)
- Funders
- National Institute for Health and Care Research (CL-2012-09-001)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Keywords
- digoxin, all-cause mortality, hospitalization, heart failure, diuretics, risk of bias, propensity score matching, observational studies, randomized controlled trials, baseline differences, heart failure severity, antiarrhythmic drugs, ejection fraction, diabetes mellitus, treatment efficacy and safety, meta-regression
- MeSH terms
- Atrial Fibrillation, Cardiotonic Agents, Digoxin, Heart Failure, Hospitalization, Humans, Treatment Outcome, Outcome Assessment, Health Care
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
