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) antagonis m with etanercept, a soluble TNF receptor, was well tolerated and that it s uppressed circulating levels of biologically active TNF for 14 days in pati ents with moderate heart failure. However, the effects of sustained TNF ant agonism in heart failure are not known. Methods and Results-We conducted a randomized, double-blind, placebo-contro lled, multidose trial of etanercept in 47 patients with NYHA class III to I V heart failure. Patients were treated with biweekly subcutaneous injection s 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 tol erated for 3 months. Treatment with etanercept led to a significant dose-de pendent improvement in left ventricular (LV) ejection fraction and LV remod eling, and there was a trend toward an improvement in patient functional st atus, as determined by clinical composite score. Conclusion-Treatment with etanercept for 3 months was safe and well-tolerat ed in patients with advanced heart failure, and it resulted in a significan t dose-dependent improvement in LV structure and function and a trend towar d improvement in patient functional status.