Safety and efficacy of a soluble P75 tumor necrosis factor receptor (enbrel, etanercept) in patients with advanced heart failure

Background-Although previous studies suggested that TNF may contribute to h eart failure progression, it is unclear whether antagonizing TNF is benefic ial in heart failure patients. Methods and Results-Eighteen NYHA class III heart failure patients were ran domized into a double-blind dose-escalation study to examine the safety and potential efficacy of etanercept, a specific TNF antagonist (Enbrel). Pati ents received placebo (6 patients) or an escalating dose (1, 4, or 10 mg/m( 2)) of etanercept (12 patients) given as a single intravenous infusion. Saf ety parameters and patient functional status were assessed at baseline and at days 1, 2, 7, and 14. There were no significant side effects or clinical ly significant changes in laboratory indices. Then was, however, a decrease in TNF bioactivity and a significant overall increase in quality-of-life s cores, 6-minute walk distance, and ejection fraction in the cohort that rec eived 4 or 10 mg/m(2) of etanercept; there was no significant change in the se parameters in the placebo group. Conclusions-A single intravenous infusi on of etanercept was safe and well tolerated in patients with NYHA class II I heart failure. These studies provide provisional evidence that suggests t hat etanercept is sufficient to lower levels of biologically active TNF and may lead to improvement in the functional status of patients with heart fa ilure.