Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure

Background An enhanced inflammatory response predicts worse outcomes in heart failure (HF). We hypothesized that administration of IL-1 (interleukin-1) receptor antagonist (anakinra) could inhibit the inflammatory response and improve peak aerobic exercise capacity in patients with recently decompensated systolic HF. Methods and Results We randomly assigned 60 patients with reduced left ventricular ejection fraction (<50%) and elevated C-reactive protein levels (>2 mg/L), within 14 days of hospital discharge, to daily subcutaneous injections with anakinra 100 mg for 2 weeks, 12 weeks, or placebo. Patients underwent measurement of peak oxygen consumption (V o 2 [mL/kg per minute]) and ventilatory efficiency (the VE/V co 2 slope). Treatment with anakinra did not affect peak V o 2 or VE/V co 2 slope at 2 weeks. At 12 weeks, patients continued on anakinra showed an improvement in peak V o 2 from 14.5 (10.5–16.6) mL/kg per minute to 16.1 (13.2–18.6) mL/kg per minute ( P =0.009 for within-group changes), whereas no significant changes occurred within the anakinra 2-week or placebo groups. The between-groups differences, however, were not statistically significant. The incidence of death or rehospitalization for HF at 24 weeks was 6%, 31%, and 30%, in the anakinra 12-week, anakinra 2-week, and placebo groups, respectively (log-rank test P =0.10). Conclusions No change in peak V o 2 occurred at 2 weeks in patients with recently decompensated systolic HF treated with anakinra, whereas an improvement was seen in those patients in whom anakinra was continued for 12 weeks. Additional larger studies are needed to validate the effects of prolonged anakinra on peak V o 2 and rehospitalization for HF. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01936909.