Targeted Anticytokine Therapy in Patients with Chronic Heart Failure: Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)

Douglas L. Mann, John J.V. McMurray, Milton Packer, Karl Swedberg, Jeffrey S. Borer, Wilson S. Colucci, Jacques Djian, Helmut Drexler, Arthur Feldman, Lars Kober, Henry Krum, Peter Liu, Markku Nieminen, Luigi Tavazzi, Dirk Jan Van Veldhuisen, Anders Waldenstrom, Marshelle Warren, Arne Westheim, Faiez Zannad, Thomas Fleming

Research output: Contribution to journalArticle

823 Scopus citations

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.

Original languageEnglish
Pages (from-to)1594-1602
Number of pages9
JournalCirculation
Volume109
Issue number13
DOIs
StatePublished - Apr 6 2004
Externally publishedYes

Keywords

  • Cytokines
  • Etanercept
  • Heart failure
  • Tumor necrosis factor

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    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. (2004). Targeted Anticytokine Therapy in Patients with Chronic Heart Failure: Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation, 109(13), 1594-1602. https://doi.org/10.1161/01.CIR.0000124490.27666.B2