Results of targeted anti-tumor necrosis factor therapy with etanercept (ENBREL) in patients with advanced heart failure.
BACKGROUND
Previously, we showed that tumor necrosis factor (TNF) antagonism with etanercept, a soluble TNF receptor, was well tolerated and that it suppressed circulating levels of biologically active TNF for 14 days in patients with moderate heart failure. However, the effects of sustained TNF antagonism in heart failure are not known.


RESULTS
We conducted a randomized, double-blind, placebo-controlled, multidose trial of etanercept in 47 patients with NYHA class III to IV heart failure. Patients were treated with biweekly subcutaneous injections of etanercept 5 mg/m(2) (n=16) or 12 mg/m(2) (n=15) or with placebo (n=16) for 3 months. Doses of 5 and 12 mg/m(2) etanercept were safe and well tolerated for 3 months. Treatment with etanercept led to a significant dose-dependent improvement in left ventricular (LV) ejection fraction and LV remodeling, and there was a trend toward an improvement in patient functional status, as determined by clinical composite score.


CONCLUSIONS
Treatment with etanercept for 3 months was safe and well-tolerated in patients with advanced heart failure, and it resulted in a significant dose-dependent improvement in LV structure and function and a trend toward improvement in patient functional status.
Bozkurt
B
B
Winters Center For Heart Failure Research, Department of Medicine, Veterans Administration Medical Center, Houston, TX 77030, USA.
Torre-Amione
G
G
Warren
M S
MS
Whitmore
J
J
Soran
O Z
OZ
Feldman
A M
AM
Mann
D L
DL
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D004311:Double-Blind Method; D000068800:Etanercept; D005260:Female; D006331:Heart Diseases / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept