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


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.
Mann
Douglas L
DL
Winters Center for Heart Failure Research, Baylor College of Medicine and the Houston VA, Houston, Tex 77030, USA. dmann@bcm.tmc.edu
McMurray
John J V
JJ
Packer
Milton
M
Swedberg
Karl
K
Borer
Jeffrey S
JS
Colucci
Wilson S
WS
Djian
Jacques
J
Drexler
Helmut
H
Feldman
Arthur
A
Kober
Lars
L
Krum
Henry
H
Liu
Peter
P
Nieminen
Markku
M
Tavazzi
Luigi
L
van Veldhuisen
Dirk Jan
DJ
Waldenstrom
Anders
A
Warren
Marshelle
M
Westheim
Arne
A
Zannad
Faiez
F
Fleming
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004198:Disease Susceptibility; D004311:Double-Blind Method; D000068800:Etanercept; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007239:Infections / Q000453:epidemiology; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D016019:Survival Analysis; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept