Targeted Anticytokine Therapy in Patients With Chronic Heart Failure: Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)
Abstract
Background— Studies in experimental models and preliminary clinical experience suggested a possible therapeutic role for the soluble tumor necrosis factor antagonist etanercept in heart failure. Methods and Results— Patients with New York Heart Association class II to IV chronic heart failure and a left ventricular ejection fraction ≤0.30 were enrolled in 2 clinical trials that differed only in the doses of etanercept used. In RECOVER, patients received placebo (n=373) or subcutaneous etanercept in doses of 25 mg every week (n=375) or 25 mg twice per week (n=375). In RENAISSANCE, patients received placebo (n=309), etanercept 25 mg twice per week (n=308), or etanercept 25 mg 3 times per week (n=308). The primary end point of each individual trial was clinical status at 24 weeks. Analysis of the effect of the 2 higher doses of etanercept on the combined outcome of death or hospitalization due to chronic heart failure from the 2 studies was also planned (RENEWAL). On the basis of prespecified stopping rules, both trials were terminated prematurely owing to lack of benefit. Etanercept had no effect on clinical status in RENAISSANCE ( P =0.17) or RECOVER ( P =0.34) and had no effect on the death or chronic heart failure hospitalization end point in RENEWAL (etanercept to placebo relative risk=1.1, 95% CI 0.91 to 1.33, P =0.33). Conclusions— The results of RENEWAL rule out a clinically relevant benefit of etanercept on the rate of death or hospitalization due to chronic heart failure.
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Clinical trials of etanercept in congestive heart failure showed no beneficial reduction in mortality or hospitalization.
“clinical trials with the TNF inhibitor etanercept yielded no beneficial reductions in mortality or hospitalization due to congestive heart failure”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [193]
Clinical studies testing the anti-TNF hypothesis revealed negative results and perhaps even increased cardiovascular events in the treatment group.
“In brief, these studies revealed negative results and perhaps even increased cardiovascular events in the treatment group.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [55]
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- Authors
- Mann, D. L., McMurray, J. J. V., Packer, M., Swedberg, K., Borer, J. S., Colucci, W. S., Djian, J., Drexler, H., Feldman, A., Kober, L., Krum, H., Liu, P., Nieminen, M., Tavazzi, L., van Veldhuisen, D. J., Waldenstrom, A., Warren, M., Westheim, A., Zannad, F., & Fleming, T.
- Affiliations
- Baylor College of Medicine (US)
- From the Winters Center for Heart Failure Research (D.L.M.), Baylor College of Medicine and the Houston VA, Houston, Tex; Department of Cardiology, Western Infirmary (J.J.V.M.), Glasgow, United Kingdom; Department of Medicine, University of Texas Dallas Southwestern Medical Center (M.P.), Dallas, Tex; Department of Medicine, Sahlgrenska University Hospital/Östra (K.S.), Göteborg, Sweden; Division of Cardiovascular Pathophysiology, Weill Medical College of Cornell University (J.S.B.), New York, NY;...
- Amgen (United States) (US)
- ORCID
- Venue
- Circulation
- Published
- 2004-04-06
- Volume
- 109
- Issue
- 13
- Pages
- 1594-1602
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2147155927
- Cited by
- 1,240
- References
- 21
- Citations by year
- 2026: 33 · 2025: 60 · 2024: 60 · 2023: 55 · 2022: 58 · 2021: 55 · 2020: 60 · 2019: 59 · 2018: 46 · 2017: 62 · 2016: 43 · 2015: 47 · 2014: 62 · 2013: 56 · 2012: 61
- FWCI
- 38.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Amgen
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- chronic heart failure, etanercept, soluble tumor necrosis factor receptor, anti-cytokine therapy, TNF antagonists, heart failure hospitalization, heart failure mortality, dose comparison
- MeSH terms
- Etanercept, Adolescent, Adult, Aged, Aged, 80 and over, Disease Susceptibility, Double-Blind Method, Female, Heart Failure, Hospitalization, Humans, Immunoglobulin G, Infections, Male, Middle Aged, Tumor Necrosis Factor-alpha, Life Tables, Survival Analysis, Treatment Failure, Receptors, Tumor Necrosis Factor
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