Targeted Anticytokine Therapy in Patients With Chronic Heart Failure

TLDR

Studies in experimental models and early clinical work suggested that the soluble tumor necrosis factor antagonist etanercept might benefit heart failure patients. The study aimed to evaluate whether higher doses of etanercept reduce death or hospitalization in patients with chronic heart failure. Patients with NYHA class II–IV heart failure and left ventricular ejection fraction ≤30 % were enrolled in two trials (RECOVER and RENAISSANCE) that compared placebo to etanercept at 25 mg weekly, twice weekly, or thrice weekly, with clinical status at 24 weeks as the primary endpoint; a planned analysis of higher doses on death/hospitalization (RENEWAL) was also included. Both trials were stopped early for lack of benefit, and etanercept showed no effect on clinical status or on the death/hospitalization endpoint (relative risk 1.1, 95 % CI 0.91–1.33, P = 0.33), ruling out a clinically relevant benefit.

Abstract

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. Methods and Results— Patients with New York Heart Association class II to IV chronic heart failure and a left ventricular ejection fraction ≤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.