(Circulation. 2001;103:1044.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
Results of Targeted Anti–Tumor Necrosis Factor Therapy With Etanercept (ENBREL) in Patients With Advanced Heart Failure
From the Winters Center For Heart Failure Research, Department of Medicine, Veterans Administration Medical Center, and the Methodist Hospital, and Baylor College of Medicine, Houston, Tex (B.B., G.T.-A., D.L.M.); the Cardiovascular Institute of the University of Pittsburgh Medical Center Health System, Pittsburgh, Pa (O.Z.S., A.M.F.); and Immunex Corporation, Seattle, Wash (M.S.W., J.W.).
Correspondence to Douglas L. Mann, MD, Winters Center for Heart Failure Research (151C), Houston VA Medical Center, 2002 Holcombe Blvd, Houston, TX 77030. E-mail dmann{at}bcm.tmc.edu
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.
Methods and 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/m2 (n=16) or 12 mg/m2 (n=15) or with placebo (n=16) for 3 months. Doses of 5 and 12 mg/m2 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.
Conclusion—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.
Key Words: heart failure • myocardial contraction • growth substances • cytokines • tumor necrosis factor
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