How to RECOVER from RENAISSANCE? The significance of the results of RECOVER, RENAISSANCE, RENEWAL and ATTACH

Two trial programmes testing an anti-cytokine medication in chronic heart failure (CHF) have been halted. In the RENAISSANCE and RECOVER trials (the combined analysis being termed RENEWAL), 2048 CHF patients were randomised to placebo or one of 3 doses of etanercept, a fusion protein directed against TNF. Within RENAISSANCE and RECOVER a clinical composite score was used to assess the clinical effects at 24 weeks (primary endpoint: alpha 0.04). Overall, the number of patients who were classified to have during the trial "improved", remained "unchanged" or "worsened" was similar for patients on placebo or any dose of etanercept (RENAISSANCE: p=0.17, RECOVER: p=0.34). In RENEWAL (combined analysis of medium and high dose etanercept vs. placebo), the primary endpoint (death or CHF hospitalisation, alpha 0.01) was not different between etanercept and placebo (RR 1.10, 95%CI 0.91 to 1.33, p=0.33). In RENEWAL, the secondary endpoint (death for any cause) was not different between etanercept and placebo (RR 1.13, 95%CI 0.86 to 1.50, p=0.39). ATTACH was a phase II, multicentre, randomised, double-blind, placebo-controlled pilot trial that aimed to evaluate the effects of infliximab (an antibody against TNF given in 2 different doses) in 150 CHF patients with stable NYHA class III or IV (in NYHA IV: