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Systematic Review Article

Digoxin and Outcomes in Patients with Heart Failure and Preserved Ejection Fraction (HFpEF) Patients: A Systematic Review and Meta- Analysis

Author(s): Seyed H. Hashemi-Shahri, Ali Aghajanloo, Vahid Ghavami, Omid Arasteh*, Amir H. Mohammadpour*, Željko Reiner and Amirhossein Sahebkar*

Volume 24, Issue 2, 2023

Published on: 30 September, 2022

Page: [191 - 200] Pages: 10

DOI: 10.2174/1389450123666220906093058

Price: $65

Abstract

Background: One of the major indications for digoxin use is the treatment of heart failure (HF). Although the clinical application of digoxin in long-term outcomes in patients with HF and reduced ejection fraction (HFrEF) patients is well explained, the association between digoxin therapy and outcomes in patients with HF and preserved ejection fraction (HFpEF) is not very clear.

Objectives: The aim of this study was to show the clinical efficacy of digoxin on long-term outcomes in subjects with HFpEF.

Methods: PubMed, Embase, Scopus and Web of Science (ISI) electronic databases were searched until May 2021 to obtain relevant studies. The primary outcome was all-cause mortality attributed to treatment with digoxin. The secondary outcomes were “all-cause hospitalization”, “hospitalization because of HF” and “all-cause mortality or hospitalization of HF”.

Results: Seven studies with more than 23000 patients with HFpEF, of which more than 4900 were treated with digoxin, fulfilled the eligibility criteria and were included in this meta-analysis. Treatment with digoxin was associated with a neutral effect on all-cause mortality (HR 1.04, 95 % CI 0.91-1.20, I2 = 57.9 %), all-cause hospitalization (HR 0.97, 95 % CI 0.88-1.07, I2 = 0.0 %), HFhospitalization (HR 0.96, 95 % CI 0.90-1.02, I2 = 41.4 %), and all-cause mortality or HFhospitalization (HR 1.07, 95 % CI 0.91-1.26, I2 = 81.2 %). In subgroup meta-analyses based on ejection fraction (EF), treatment with digoxin did not significantly alter these outcomes in each subset of patients.

Conclusion: The results of this meta-analysis suggest that digoxin does not have any significant effect on long-term outcomes of HFpEF patients, including “all-cause mortality”, “all-cause hospitalization”, “hospitalization because of HF” and “all-cause mortality or hospitalization of HF”.

Keywords: Digoxin, heart failure with preserved ejection fraction, HFpEF, mortality, hospitalization, symptomatic therapy.

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[1]
Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2016; 37(27): 2129-200.
[http://dx.doi.org/10.1093/eurheartj/ehw128] [PMID: 27206819]
[2]
Yancy CW, Jessup M, Bozkurt B, et al. ACCF/AHA guideline for the management of heart failure. J Am Coll Cardiol 2013; 62(16): e147-239.
[http://dx.doi.org/10.1016/j.jacc.2013.05.019] [PMID: 23747642]
[3]
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. J Am Coll Cardiol 1993; 22(4): 955-62.
[http://dx.doi.org/10.1016/0735-1097(93)90403-N] [PMID: 8409069]
[4]
Packer M, Gheorghiade M, Young JB, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. N Engl J Med 1993; 329(1): 1-7.
[http://dx.doi.org/10.1056/NEJM199307013290101] [PMID: 8505940]
[5]
Group DI. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336(8): 525-33.
[http://dx.doi.org/10.1056/NEJM199702203360801] [PMID: 9036306]
[6]
Ahmed A, Rich M, Fleg J. Effects of digoxin on morbidity and mortality in diastolic heart failure. The ancillary digitalis investigation group trial. Circulation 2006; 114(5): 397-403.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.628347]
[7]
Virgadamo S, Charnigo R, Darrat Y, Morales G, Elayi CS. Digoxin: A systematic review in atrial fibrillation, congestive heart failure and post myocardial infarction. World J Cardiol 2015; 7(11): 808-16.
[http://dx.doi.org/10.4330/wjc.v7.i11.808] [PMID: 26635929]
[8]
Ahmed A, Rich MW, Love TE, et al. Digoxin and reduction in mortality and hospitalization in heart failure: A comprehensive post hoc analysis of the DIG trial. Eur Heart J 2006; 27(2): 178-86.
[http://dx.doi.org/10.1093/eurheartj/ehi687] [PMID: 16339157]
[9]
Ahmed A, Bourge RC, Fonarow GC, et al. Digoxin use and lower 30-day all-cause readmission for Medicare beneficiaries hospitalized for heart failure. Am J Med 2014; 127(1): 61-70.
[http://dx.doi.org/10.1016/j.amjmed.2013.08.027] [PMID: 24257326]
[10]
Lam PH, Bhyan P, Arundel C, et al. Digoxin use and lower risk of 30-day all-cause readmission in older patients with heart failure and reduced ejection fraction receiving β-blockers. Clin Cardiol 2018; 41(3): 406-12.
[http://dx.doi.org/10.1002/clc.22889] [PMID: 29569405]
[11]
Qamer SZ, Malik A, Bayoumi E, et al. Digoxin use and outcomes in patients with heart failure with reduced ejection fraction. Am J Med 2019; 132(11): 1311-9.
[http://dx.doi.org/10.1016/j.amjmed.2019.05.012] [PMID: 31150644]
[12]
Meyer P, White M, Mujib M, et al. Digoxin and reduction of heart failure hospitalization in chronic systolic and diastolic heart failure. Am J Cardiol 2008; 102(12): 1681-6.
[http://dx.doi.org/10.1016/j.amjcard.2008.05.068] [PMID: 19064024]
[13]
Hashim T, Elbaz S, Patel K, et al. Digoxin and 30-day all-cause hospital admission in older patients with chronic diastolic heart failure. Am J Med 2014; 127(2): 132-9.
[http://dx.doi.org/10.1016/j.amjmed.2013.08.006] [PMID: 24067296]
[14]
Phan TT, Shivu GN, Abozguia K, et al. Impaired heart rate recovery and chronotropic incompetence in patients with heart failure with preserved ejection fraction. Circ Heart Fail 2010; 3(1): 29-34.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.109.877720] [PMID: 19917649]
[15]
Borlaug BA, Melenovsky V, Russell SD, et al. Clinical perspective. Circulation 2006; 114(20): 2138-47.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.632745] [PMID: 17088459]
[16]
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009; 6(7): e1000097.
[http://dx.doi.org/10.1371/journal.pmed.1000097] [PMID: 19621072]
[17]
Islam MM, Iqbal U, Walther B, et al. Benzodiazepine use and risk of dementia in the elderly population: A systematic review and meta-analysis. Neuroepidemiology 2016; 47(3-4): 181-91.
[http://dx.doi.org/10.1159/000454881] [PMID: 28013304]
[18]
Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327(7414): 557-60.
[http://dx.doi.org/10.1136/bmj.327.7414.557] [PMID: 12958120]
[19]
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50(4): 1088-101.
[http://dx.doi.org/10.2307/2533446] [PMID: 7786990]
[20]
Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315(7109): 629-34.
[http://dx.doi.org/10.1136/bmj.315.7109.629] [PMID: 9310563]
[21]
Ezekowitz JA, Lee DS, Tu JV, Newman AM, McAlister FA. Comparison of one-year outcome (death and rehospitalization) in hospitalized heart failure patients with left ventricular ejection fraction >50% versus those with ejection fraction <50%. Am J Cardiol 2008; 102(1): 79-83.
[http://dx.doi.org/10.1016/j.amjcard.2008.02.102] [PMID: 18572040]
[22]
Lam PH, Packer M, Gill GS, et al. Digoxin initiation and outcomes in patients with heart failure with preserved ejection fraction. Am J Med 2020; 133(10): 1187-94.
[http://dx.doi.org/10.1016/j.amjmed.2020.02.040] [PMID: 32272101]
[23]
Llàcer P, Núñez J, Bayés-Genís A, et al. Digoxin and prognosis of heart failure in older patients with preserved ejection fraction: Importance of heart rate. Results from an observational and multicenter study. Eur J Intern Med 2019; 60: 18-23.
[http://dx.doi.org/10.1016/j.ejim.2018.10.010] [PMID: 30360944]
[24]
Migaj J. Kałużny-Oleksy M, Nessler J, et al. Impact of digoxin on risk of death in heart failure patients treated with\beta-blockers: results from Polish part of ESC heart failure long-term registry. Kardiol Pol 2018; 76(7): 1064-72.
[http://dx.doi.org/10.5603/KP.a2018.0059]
[25]
Savarese G, Rosano GMC, Hage C, Hauptman PJ, Perrone-Filardi P, Lund LH. Mortality and morbidity in heart failure patients exposed to Digoxin: Comprehensive data according to ejection fraction and atrial fibrillation in 41881 patients from the Swedish heart failure register. Eur Heart J 2016; 37: 795.
[26]
Tran RH, Aldemerdash A, Chang P, et al. Guideline-directed medical therapy and survival following hospitalization in patients with heart failure. Pharmacotherapy 2018; 38(4): 406-16.
[http://dx.doi.org/10.1002/phar.2091] [PMID: 29423950]
[27]
Ahmed A, Pitt B, Rahimtoola SH, et al. Effects of digoxin at low serum concentrations on mortality and hospitalization in heart failure: A propensity-matched study of the DIG trial. Int J Cardiol 2008; 123(2): 138-46.
[http://dx.doi.org/10.1016/j.ijcard.2006.12.001] [PMID: 17382417]
[28]
Ahmed A, Waagstein F, Pitt B, et al. Effectiveness of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group trial. Am J Cardiol 2009; 103(1): 82-7.
[http://dx.doi.org/10.1016/j.amjcard.2008.06.068] [PMID: 19101235]
[29]
Abdul-Rahim AH, Shen L, Rush CJ, Jhund PS, Lees KR, McMurray JJV. Effect of digoxin in patients with heart failure and mid-range (borderline) left ventricular ejection fraction. Eur J Heart Fail 2018; 20(7): 1139-45.
[http://dx.doi.org/10.1002/ejhf.1160] [PMID: 29493058]
[30]
Weerakoon S, Tsimploulis A, Arundel C, et al. Clinical effectiveness of digoxin in hospitalized older patients with heart failure and preserved ejection fraction: A propensity-matched study of medicare-linked OPTIMIZE-HF Circulation 2016; 134(suppl_1): A20752-A.
[31]
Singh S, Moore H, Karasik PE, et al. Digoxin initiation and outcomes in patients with heart failure (HFrEF and HFpEF) and atrial fibrillation. Am J Med 2020; 133(12): 1460-70.
[http://dx.doi.org/10.1016/j.amjmed.2020.05.030] [PMID: 32603789]
[32]
Gorelik O, Almoznino-Sarafian D, Shteinshnaider M, et al. Clinical variables affecting survival in patients with decompensated diastolic versus systolic heart failure. Clin Res Cardiol 2009; 98(4): 224-32.
[http://dx.doi.org/10.1007/s00392-009-0746-1] [PMID: 19219395]
[33]
Macía-Rodríguez C, Páez-Guillán E, Alende-Castro V, et al. Five-year outcomes of heart failure with preserved ejection fraction. Open Cardiovasc Med J 2020; 14(1): 18-26.
[http://dx.doi.org/10.2174/18741924020140100018]
[34]
Tehrani F, Phan A, Chien CV, Morrissey RP, Rafique AM, Schwarz ER. Value of medical therapy in patients >80 years of age with heart failure and preserved ejection fraction. Am J Cardiol 2009; 103(6): 829-33.
[http://dx.doi.org/10.1016/j.amjcard.2008.11.047] [PMID: 19268740]
[35]
Shotan A, Gottlieb S, Behar S, et al. Late mortality and determinants in patients with heart failure and preserved systolic left ventricular function: The Israel Nationwide Heart Failure Survey. Isr Med Assoc J 2007; 9(4): 234-8.
[36]
Group DI. Rationale, design, implementation, and baseline characteristics of patients in the dig trial: A large, simple, long-term trial to evaluate the effect of digitalis on mortality in heart failure. Control Clin Trials 1996; 17(1): 77-97.
[http://dx.doi.org/10.1016/0197-2456(95)00065-8] [PMID: 8721804]
[37]
Yang Y, Guo S, Huang Z, et al. Decreased mortality with Beta-blocker therapy in HFpEF patients associated with atrial fibrillation. Cardiol Res Pract 2020; 2020: 3059864.
[http://dx.doi.org/10.1155/2020/3059864]

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