Published online before print March 15, 2004, doi: 10.1161/01.CIR.0000124490.27666.B2
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(Circulation. 2004;109:1594-1602.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Targeted Anticytokine Therapy in Patients With Chronic Heart Failure
Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)
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; Division of Cardiology, Boston Medical Center (W.S.C.), Boston, Mass; Wyeth Research (J.D.), Paris, France; Medizinische Hochschule (H.D.), Hannover, Germany; Division of Cardiology, University of Pittsburgh Medical Center (A.F.), Pittsburgh, Pa; Gentofte Hospital/University of Copenhagen (L.K.), Department of Cardiology, Niels Andersens Vej, Denmark; Clinical Pharmacology Unit, Alfred Hospital (H.K.), Prahran, Victoria, Australia; The Toronto Hospital (P.L.), Cardiology Research, Toronto, Ontario, Canada; Division of Cardiology, Helsinki University Central Hospital (M.N.), Haartmaninkatu, Helsinki, Finland; Divisione di Cardiologia, Policlinico San Matteo-IRCCS (L.T.), Pavia, Italy; Academisch Ziekenhuis Groningen (D.J.v.V.), Cardio Research, GZ Groningen, The Netherlands; Department of Medicine, Umea University Hospital (A.W.), Umea, Sweden; Amgen Inc (M.W.), Thousand Oaks, Calif; Medicinsk Klinikk (A.W.), Hjertemedisinsk Avd, Ullevål Sykehus, Oslo, Norway; Centre d’Investigation Clinique (F.Z.), Hopital Jeanne d’Arc, Dommartin Les Toul Cedex, France; and Department of Biostatistics (T.F.), University of Washington, Seattle, Wash.
Correspondence to Douglas L Mann, MD, Winters Center for Heart Failure Research, MS 524, 6565 Fannin, Houston, TX 77030. E-mail dmann{at}bcm.tmc.edu
Received December 20, 2003; revision received January 26, 2004; accepted January 26, 2004.
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.
Key Words: heart failure • tumor necrosis factor • etanercept • cytokines
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