Digoxin discontinuation and outcomes in patients with heart failure with reduced ejection fraction
Open accessAbstract
Background The deleterious effects of discontinuation of digoxin on outcomes in ambulatory patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) receiving angiotensin-converting enzyme inhibitors are well-documented.Objectives The authors sought to determine the relationship between digoxin discontinuation and outcomes in hospitalized patients with HFrEF receiving more contemporary guideline-directed medical therapies including beta-blockers and mineralocorticoid receptor antagonists.Methods Of the 11,900 hospitalized patients with HFrEF (EF ≤45%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 3,499 received pre-admission digoxin, which was discontinued in 721 patients. Using propensity scores for digoxin discontinuation, estimated for each of the 3,499 patients, a matched cohort of 698 pairs of patients, balanced on 50 baseline characteristics (mean age 76 years; mean EF 28%; 41% women; 13% African American; 65% on beta-blockers) was assembled.Results Four-year post-discharge, digoxin discontinuation was associated with significantly higher risks of HF readmission (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.05 to 1.39; p = 0.007), all-cause readmission (HR: 1.16; 95% CI: 1.04 to 1.31; p = 0.010), and the combined endpoint of HF readmission or all-cause mortality (HR: 1.20; 95% CI: 1.07 to 1.34; p = 0.002), but not all-cause mortality (HR: 1.09; 95% CI: 0.97 to 1.24; p = 0.163). Discontinuation of digoxin was associated with a significantly higher risk of all 4 outcomes at 6 months and 1 year post-discharge. At 30 days, digoxin discontinuation was associated with higher risks of all-cause mortality (HR: 1.80; 95% CI: 1.26 to 2.57; p = 0.001) and the combined endpoint (HR: 1.36; 95% CI: 1.09 to 1.71; p = 0.007), but not of HF readmission (HR: 1.19; 95% CI: 0.90 to 1.59; p = 0.226) or all-cause readmission (HR: 1.03; 95% CI: 0.84 to 1.26; p = 0.778).Conclusions Among hospitalized older patients with HFrEF on more contemporary guideline-directed medical therapies, discontinuation of pre-admission digoxin therapy was associated with poor outcomes.
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Among hospitalized older patients with HFrEF who are receiving guideline-directed medical therapies, discontinuation of preadmission digoxin therapy might have deleterious effects.
“Among hospitalized older patients with HFrEF who are receiving guideline-directed medical therapies, discontinuation of preadmission digoxin therapy might have deleterious effects.”
From CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction (2021) · cites this paper as [76]
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- Authors
- Malik, A., Masson, R., Singh, S., Wu, W.-C., Packer, M., Pitt, B., Waagstein, F., Morgan, C. J., Allman, R. M., Fonarow, G. C., & Ahmed, A.
- Affiliations
- Georgetown University (US)
- Brown University (US)
- Baylor University Medical Center (US)
- University of Michigan (US)
- University of Gothenburg (SE)
- Veterans Health Administration (US)
- George Washington University (US)
- University of California, Los Angeles (US)
- Corresponding author
- Ahmed, Ali
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 74
- Issue
- 5
- Pages
- 617-627
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC10465068
- OpenAlex
- W2965239074
- Cited by
- 55
- References
- 45
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 11 · 2023: 5 · 2022: 13 · 2021: 6 · 2020: 10 · 2019: 4
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (R01-HL085561, R01-HL085561-S, R01-HL097047)
- Amgen
- Pfizer
- AstraZeneca
- GlaxoSmithKline (R01-HL085561, R01-HL097047)
- Sanofi
- Gilead Sciences
- University of Pittsburgh
- Daiichi-Sankyo
- National Institutes of Health
- Relypsa
- National Heart, Lung, and Blood Institute (R01-HL085561-S, R01HL097047, R01HL085561)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Keywords
- heart failure with reduced ejection fraction, heart failure readmission, all-cause mortality, guideline-directed medical therapy, beta-blockers, mineralocorticoid receptor antagonists, ACE inhibitors, hospitalized heart failure patients, post-discharge outcomes, propensity score matching, Medicare beneficiaries
- MeSH terms
- Aged, Cardiotonic Agents, Cause of Death, Digoxin, Female, Heart Failure, Humans, Male, Outpatients, Patient Readmission, Registries, Retrospective Studies, Risk Factors, Stroke Volume, United States, Survival Rate, Treatment Outcome, Withholding Treatment, Propensity Score
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