Targeted anticytokine therapy in patients with chronic Heart failure: Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)

• Published in: Circulation (New York, N.Y.) Vol. 109; no. 13; pp. 1594 - 1602
• Main Authors: MANN, Douglas L, MCMURRAY, John J. V, KRUM, Henry, LIU, Peter, NIEMINEN, Markku, TAVAZZI, Luigi, VAN VELDHUISEN, Dirk Jan, WALDENSTROM, Anders, WARREN, Marshelle, WESTHEIM, Arne, ZANNAD, Faiez, FLEMING, Thomas, PACKER, Milton, SWEDBERG, Karl, BORER, Jeffrey S, COLUCCI, Wilson S, DJIAN, Jacques, DREXLER, Helmut, FELDMAN, Arthur, KOBER, Lars
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 06.04.2004
• Subjects: 80 and over; Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blood and lymphatic vessels; Cardiac and Cardiovascular Systems; Cardiology. Vascular system; Congestive/drug therapy/mortality; Disease Susceptibility; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Double-Blind Method; Etanercept; Female; Heart Failure; Heart Failure - drug therapy; Heart Failure - mortality; Hospitalization - statistics & numerical data; Humans; Immunoglobulin G - administration & dosage; Immunoglobulin G - adverse effects; Immunoglobulin G - therapeutic use; Immunoglobulin G/administration & dosage/adverse effects/therapeutic use; Infection - epidemiology; Kardiologi; Life Tables; Male; Medical sciences; Middle Aged; Receptors; Receptors, Tumor Necrosis Factor - administration & dosage; Receptors, Tumor Necrosis Factor - therapeutic use; Survival Analysis; Treatment Failure; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor/administration & dosage/therapeutic use; Human; Heart failure; Treatment; Etanercept; tumor necrosis factor; Heart disease; Cardiovascular disease; cytokines; 80 and over; Heart Failure; Tumor Necrosis Factor/administration & dosage/therapeutic use; Receptors; Aged; Congestive/drug therapy/mortality
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.0000124490.27666.B2

Studies in experimental models and preliminary clinical experience suggested a possible therapeutic role for the soluble tumor necrosis factor antagonist etanercept in heart failure. Patients with New York Heart Association class II to IV chronic heart failure and a left ventricular ejection fraction < or =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). The results of RENEWAL rule out a clinically relevant benefit of etanercept on the rate of death or hospitalization due to chronic heart failure.