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 Յ0.30 were enrolled in 2 clinical trials that differed only in the doses of etanercept used. In RECOVER, patients received placebo (nϭ373) or subcutaneous etanercept in doses of 25 mg every week (nϭ375) or 25 mg twice per week (nϭ375). In RENAISSANCE, patients received placebo (nϭ309), etanercept 25 mg twice per week (nϭ308), or etanercept 25 mg 3 times per week (nϭ308). 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 (Pϭ0.17) or RECOVER (Pϭ0.34) and had no effect on the death or chronic heart failure hospitalization end point in RENEWAL (etanercept to placebo relative riskϭ1.1, 95% CI 0.91 to 1.33, Pϭ0.33). 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.

Background-Anemia is often observed in patients with chronic heart failure (CHF), but its implications for patient outcomes are not well understood. The goal of this study was to investigate the relationship between anemia, severity of CHF, and clinical outcomes. Methods and Results-Hemoglobin concentration (Hb) was measured in 912 subjects with CHF enrolled in the Randomized Etanercept North American Strategy to Study Antagonism of Cytokines (RENAISSANCE) trial. In a subgroup of 69 subjects, cardiac MRI was performed at randomization and 24 weeks later. Anemia (Hb Յ12.0 g/dL) was present in 12% of subjects. Cox regression analysis indicated that for every 1-g/dL-higher baseline Hb, the risk of mortality was 15.8% lower (Pϭ0.0009) and the risk of mortality or hospitalization for heart failure was 14.2% lower (PϽ0.0001). Greater CHF severity was associated with significantly lower Hb concentrations. An increase in Hb over time was associated with a decrease in left ventricular mass and lower mortality, whereas a decrease in Hb over time was associated with an increase in left ventricular mass and higher mortality. In multivariate analysis, anemia remained a significant, independent predictor of death or hospitalization for heart failure, with both outcomes being significantly higher in all NYHA classes. Conclusions-Anemia is frequently present in patients with CHF. Lower Hb is associated with greater disease severity, a greater left ventricular mass index, and higher hospitalization and mortality rates.