TY - JOUR

T1 - Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)

AU - Mann, Douglas L

AU - McMurray, John J V

AU - Packer, Milton

AU - Swedberg, Karl

AU - Borer, Jeffrey S

AU - Colucci, Wilson S

AU - Djian, Jacques

AU - Drexler, Helmut

AU - Feldman, Arthur

AU - Køber, Lars Valeur

AU - Krum, Henry

AU - Liu, Peter

AU - Nieminen, Markku

AU - Tavazzi, Luigi

AU - van Veldhuisen, Dirk Jan

AU - Waldenstrom, Anders

AU - Warren, Marshelle

AU - Westheim, Arne

AU - Zannad, Faiez

AU - Fleming, Thomas

N1 - Keywords: Adolescent; Adult; Aged; Aged, 80 and over; Disease Susceptibility; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Immunoglobulin G; Infection; Life Tables; Male; Middle Aged; Receptors, Tumor Necrosis Factor; Survival Analysis; Treatment Failure; Tumor Necrosis Factor-alpha

PY - 2004

Y1 - 2004

N2 - 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 < 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). 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.

AB - 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 < 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). 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.

U2 - 10.1161/01.CIR.0000124490.27666.B2

DO - 10.1161/01.CIR.0000124490.27666.B2

M3 - Journal article

C2 - 15023878

VL - 109

SP - 1594

EP - 1602

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 13

ER -