Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: Experiences from MERIT-HF
Abstract
Background The objective of the current study was to examine the efficacy and tolerability of the beta-blocker metoprolol succinate controlled release/extended release (CR/XL) in patients with diabetes in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF).Methods The Cox proportional hazards model was used to calculate hazard ratios (HR) for convenience expressed as relative risks (risk reduction = 1-HR), and 95% confidence intervals (CI).Results The risk of hospitalization for heart failure was 76% higher in diabetics compared to non-diabetics (95% CI 38% to 123%). Metoprolol CR/XL was well tolerated and reduced the risk of hospitalization for heart failure by 37% in the diabetic group (95% CI 53% to 15%), and by 35% in the non-diabetic group (95% CI 48% to 19%). Pooling of mortality data from the Cardiac Insufficiency Bisoprolol Study II (CIBIS II), MERIT-HF, and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) showed similar survival benefits in patients with diabetes (25%; 95% CI 40% to 4%) and without diabetes (36%; 95% CI 44% to 27%); test of diabetes by treatment interaction was non-significant. Adverse events were reported more often on placebo than on metoprolol CR/XL.Conclusions Patients with heart failure and diabetes have a much higher risk of hospitalization than patients without diabetes. Regardless of diabetic status, a highly significant reduction in hospitalizations for heart failure was observed with metoprolol CR/XL therapy, which was very well tolerated also by patients with diabetes. Furthermore, the pooled data showed a statistically significant survival benefit in patients with diabetes.
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The coexistence of type 2 diabetes mellitus and heart failure, either with reduced or preserved ejection fraction, is frequent, affecting 30-40% of patients.
“The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients)”
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 [37]
The highest prevalence of T2DM was seen in trials of acute HF, around 40%.
“The highest prevalence of T2DM was seen in trials of acute HF (around 40%).”
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 [37]
In clinical trials of chronic HF patients, the prevalence of T2DM was around 30%, irrespective of HF phenotype.
“In clinical trials of chronic HF patients, the prevalence of T2DM was around 30%, irrespective of HF phenotype (i.e.HFrEF and HFpEF) (Table 3).31 -48”
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 [37]
Clinical trial results are somewhat conflicting regarding the risk of all-cause and cardiovascular mortality attributed to T2DM in HF patients, but most clinical trials reported an increased risk of death in patients with concurrent T2DM and HF.
“Clinical trial results are somewhat conflicting regarding the risk of all-cause and CV mortality attributed to T2DM in HF patients, but most clinical trials reported an increased risk of death in patients with concurrent T2DM and HF (Table 5).1,31 -35,37,40,42,44,45,69,88-92”
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 [37]
Subgroup analyses of large HF trials show that beta-blockers reduce mortality and hospitalization and improve symptoms in moderate to severe HF, irrespective of T2DM.
“Subgroup analyses of large HF trials show that beta-blockers reduce mortality and hospitalization and improve symptoms in moderate to severe HF, irrespectively of T2DM.37,152,153”
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 [37]
The MERIT-HF trial reported similar efficacy and safety of metoprolol succinate in patients with and without T2DM.
“The MERIT-HF trial reported similar efficacy and safety of metoprolol succinate in patients with and ©2018 The Authors European Journal of Heart Failure ©2018 European Society of Cardiology without T2DM.37”
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 [37]
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- Authors
- Deedwania, P. C., Giles, T. D., Klibaner, M., Ghali, J. K., Herlitz, J., Hildebrandt, P., Kjekshus, J., Spinar, J., Vitovec, J., Stanbrook, H., & Wikstrand, J.
- Affiliations
- Veterans Health Administration (US)
- Louisiana State University (US)
- AstraZeneca (United States) (US)
- Sahlgrenska University Hospital (SE)
- Oslo University Hospital (NO)
- Corresponding author
- Deedwania, Prakash C.
- Venue
- American Heart Journal
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 149
- Issue
- 1
- Pages
- 159-167
- ISSN
- 0002-8703 (ISSN-L)
- OpenAlex
- W1980524591
- Cited by
- 143
- References
- 21
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 7 · 2020: 8 · 2019: 10 · 2018: 6 · 2017: 7 · 2016: 10 · 2015: 7 · 2014: 11 · 2013: 2 · 2012: 2
- FWCI
- 9.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Borås Academic Digital Archive (University of Borås) (submittedVersion)
- 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
- metoprolol succinate, beta-blockers, chronic heart failure, diabetes mellitus, heart failure hospitalization, survival benefit, drug tolerability, adverse events, Copernicus
- MeSH terms
- Adrenergic beta-Antagonists, Adult, Aged, Delayed-Action Preparations, Diabetes Mellitus, Double-Blind Method, Female, Heart Failure, Hospitalization, Humans, Male, Metoprolol, Middle Aged, Risk, Proportional Hazards Models, Survival Analysis, Diabetes Complications
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