The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial
Open accessAbstract
Objectives This was a retrospective analysis to determine the effect of diabetes on outcome in patients with advanced heart failure (HF), and to determine the effect of beta-blockade in patients with HF with and without diabetes mellitus.Background In chronic HF the impact on clinical outcomes and therapeutic response of the prevalent comorbid condition diabetes mellitus has not been extensively investigated.Methods We assessed the impact of diabetes on prognosis and effectiveness of beta-blocker therapy with bucindolol in patients with HF enrolled in the Beta-Blocker Evaluation of Survival Trial (BEST). We conducted a retrospective analysis to examine the prognosis of patients with advanced HF with and without diabetes, and the effect of beta-blocker therapy on mortality and HF progression or myocardial infarction (MI). The database was the 2,708 patients with advanced HF (36% with diabetes and 64% without diabetes) who were randomized to the beta-blocker bucindolol or placebo in BEST and followed for mortality, hospitalization, and MI for an average of two years.Results Patients with diabetes had more severe chronic HF and more coronary risk factors than patients without diabetes. Diabetes was independently associated with increased mortality in patients with ischemic cardiomyopathy (adjusted hazard ratio 1.33, 95% confidence interval 1.12 to 1.58, p = 0.001), but not in those with a nonischemic etiology (adjusted hazard ratio 0.98, 95% confidence interval 0.74 to 1.30, p = 0.89). Compared with patients without diabetes, in diabetic patients beta-blocker therapy was at least as effective in reducing death or HF hospitalizations, total hospitalizations, HF hospitalizations, and MI. Ventricular function and physiologic responses to beta-blockade were similar in patients with and without diabetes.Conclusions Diabetes worsens prognosis in patients with advanced HF, but this worsening appears to be limited to patients with ischemic cardiomyopathy. In advanced HF beta-blockade is effective in reducing major clinical end points in patients with and without diabetes.
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In the EMPEROR-Preserved trial, empagliflozin reduced the risk of the primary outcome of cardiovascular death or heart failure hospitalization by 21%, mainly related to a 29% lower risk of heart failure hospitalization.
“Compared with placebo, empagliflozin reduced the risk of the primary outcome, a composite of CV death or hospitalization for HF, by 21%, which was mainly related to a 29% lower risk of hospitalization for HF.530”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [530]
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 [94]
The majority of the available data suggests that T2DM is associated with higher risk of mortality in both patients of ischaemic and non-ischaemic aetiology.
“The majority of the available data suggests that T2DM is associated with higher risk of mortality in both patients of ischaemic and non-ischaemic aetiology (Table 6).29,88,94,96 -99”
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 [94]
In the BEST trial, T2DM was an independent risk factor for death from pump failure.
“In the BEST trial, T2DM was an independent risk factor for death from pump failure.94”
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 [94]
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- Authors
- Domanski, M., Krause-Steinrauf, H., Deedwania, P., Follmann, D., Ghali, J. K., Gilbert, E., Haffner, S., Katz, R., Lindenfeld, J., Lowes, B. D., Martin, W., McGrew, F., & Bristow, M. R.
- Affiliations
- National Institutes of Health (US)
- National Heart, Lung, and Blood Institute (US)
- Fresno VA Medical Center (US)
- University of Utah (US)
- The University of Texas at San Antonio Health Science Center (US)
- George Washington University (US)
- University of Colorado Denver (US)
- St. Louis VA Medical Center (US)
- Baptist Memorial Hospital (US)
- Corresponding author
- Domanski, Michael
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 42
- Issue
- 5
- Pages
- 914-922
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2014986461
- Cited by
- 215
- References
- 34
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 18 · 2019: 10 · 2018: 13 · 2017: 17 · 2016: 12 · 2015: 10 · 2014: 17 · 2013: 9 · 2012: 10
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Heart, Lung, and Blood Institute
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Keywords
- diabetes mellitus, advanced heart failure, beta-blocker therapy, bucindolol, ischemic cardiomyopathy, mortality, heart failure hospitalization, myocardial infarction, prognosis, comorbidities
- MeSH terms
- Adrenergic beta-Antagonists, Adult, Aged, Aged, 80 and over, Cause of Death, Female, Heart Failure, Hospitalization, Humans, Male, Middle Aged, Prognosis, Propanolamines, Retrospective Studies, Risk Factors, Severity of Illness Index, Proportional Hazards Models, Survival Analysis, Heart Transplantation, Ventricular Function, Treatment Outcome, Disease Progression, Diabetes Complications
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