Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure: Results From REDHART (Recently Decompensated Heart Failure Anakinra Response Trial)

Abstract

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 (Vo₂ [mL/kg per minute]) and ventilatory efficiency (the VE/Vco₂ slope). Treatment with anakinra did not affect peak Vo₂ or VE/Vco₂ slope at 2 weeks. At 12 weeks, patients continued on anakinra showed an improvement in peak Vo₂ 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 Vo₂ 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 Vo₂ and rehospitalization for HF.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936909.

Keywords: heart failure; heart failure, systolic; inflammation; interleukin-1; myocardial infarction.

Figure 1

Screening and enrollment of patients

Figure 2. Effects of Treatment on Peak VO₂ and VE/VCO₂ slope

VO₂ = volume of oxygen consumption; VCO₂ = volume of carbon dioxide production. Columns represent median values (vertical bars represent interquartile ranges).

Figure 3. Effects of Treatment on Plasma C-reactive Protein Levels

CRP = C-reactive protein. Columns represent median values (vertical bars represent interquartile ranges) using a logarithmic scale.

Figure 4. Effects of Treatment on left ventricular volume and systolic and diastolic function

LVEDV = left ventricular end-diastolic volume; LVEF = left ventricular ejection fraction; E = early mitral pulsed-wave Doppler flow velocity; E′ early mitral annulus tissue pulsed-wave Doppler velocity. Columns represent median values (vertical bars represent interquartile ranges).

Figure 5. Effects of Treatment on Quality of Life Measures

DASI = Duke Activity Status Index; MLWHF = Minnesota Living with Heart Failure Questionnaire. Columns represent median values (vertical bars represent interquartile ranges).

Figure 6. Effects of Treatment on Survival Free of Hospital Readmission for HF

The incidence of death or readmission for HF at 24 weeks was 30% in the placebo group, 31% in the group treated with anakinra for 2 weeks, and 6% in the group treated with anakinra 12 weeks (Log-rank P test P=0.10). HF = Heart failure.