Efficacy and safety of digoxin in patients with heart failure and reduced ejection fraction according to diabetes status: an analysis of the Digitalis Investigation Group (DIG) trial
Abstract
Background Digoxin is recommended in symptomatic heart failure patients with reduced ejection fraction (HF-REF) in sinus rhythm and refractory to other evidence-based therapy. Although HF-REF patients with diabetes have worse functional status than those without, the effects of digoxin have not been specifically evaluated according to diabetes status.Methods We examined the efficacy and safety of digoxin in HF-REF patients with and without diabetes in the Digitalis Investigation Group trial. Mortality from all-cause, cardiovascular (CV) causes and heart failure (HF), along with HF hospitalisation and suspected digoxin toxicity were analyzed according to diabetes status and randomised treatment assignment.Results Of the 6800 patients, those with diabetes (n=1933) were older, more often women, had worse clinical status and more co-morbidity than those without diabetes. All-cause and CV mortality were higher in patients with diabetes than in those without and digoxin did not reduce mortality in either sub-group. The rate of HF hospitalization (per 100 person-years) in patients with diabetes was higher than in those without and was reduced by digoxin in both patient groups: diabetes - placebo 20.5 and digoxin 16.0 (HR 0.79, 95% CI: 0.68-0.91); no diabetes - placebo 12.7 and digoxin 8.7 (HR 0.69, 0.62-0.77); interaction p=0.14. Suspected digoxin toxicity in patients randomised to digoxin was more common among patients with diabetes than without (6.5% versus 5.8%), as was hospitalisation for digoxin toxicity (1.4% versus 0.8%).Conclusion Added to an ACE inhibitor, digoxin reduced HF hospitalisation in HF-REF patients with and without diabetes without a substantial risk of toxicity.
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In three early clinical trials (SOLVD, BEST, and DIG), the risk appeared to be confined to those with an ischaemic aetiology.
“In three early clinical trials (SOLVD, 98 BEST, 94 and DIG 102 )t h er i s k appeared to be confined to those with an ischaemic aetiology.”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [102]
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- Authors
- Abdul-Rahim, A. H., MacIsaac, R. L., Jhund, P. S., Petrie, M. C., Lees, K. R., & McMurray, J. J. V.
- Affiliations
- University of Glasgow (GB)
- Golden Jubilee National Hospital (GB)
- Corresponding author
- McMurray, John J.V.
- Venue
- International Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 209
- Pages
- 310-316
- ISSN
- 0167-5273 (ISSN-L)
- OpenAlex
- W2290401299
- Cited by
- 29
- References
- 17
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 1
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Funders
- Medical Research Council (MR/N003403/1)
- 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 › Cardiovascular Function and Risk Factors
- Keywords
- digoxin, heart failure with reduced ejection fraction, diabetes mellitus, Digitalis Investigation Group trial, heart failure hospitalization, digoxin toxicity, all-cause mortality, cardiovascular mortality, ACE inhibitors, subgroup analysis
- MeSH terms
- Aged, Cardiotonic Agents, Diabetes Mellitus, Digitalis, Digoxin, Female, Heart Failure, Hospitalization, Humans, Hyperkalemia, Male, Middle Aged, Retrospective Studies, Risk Factors, Stroke Volume, Treatment Outcome
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