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

Benjamin W. Van Tassell, Justin Canada, Salvatore Carbone, Cory Trankle, Leo Buckley, Claudia Oddi Erdle, Nayef A. Abouzaki, Dave Dixon, Dinesh Kadariya, Sanah Christopher, Aaron Schatz, Jessica Regan, Michele Viscusi, Marco Del Buono, Ryan Melchior, Pranav Mankad, Juan Lu, Robin Sculthorpe, Giuseppe Biondi-Zoccai, Edward LesnefskyRoss Arena, Antonio Abbate

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalCirculation. Heart failure
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 1 2017

Keywords

  • heart failure
  • heart failure, systolic
  • inflammation
  • interleukin-1
  • myocardial infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Van Tassell, B. W., Canada, J., Carbone, S., Trankle, C., Buckley, L., Oddi Erdle, C., Abouzaki, N. A., Dixon, D., Kadariya, D., Christopher, S., Schatz, A., Regan, J., Viscusi, M., Del Buono, M., Melchior, R., Mankad, P., Lu, J., Sculthorpe, R., Biondi-Zoccai, G., ... Abbate, A. (2017). Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure: Results From REDHART (Recently Decompensated Heart Failure Anakinra Response Trial). Circulation. Heart failure, 10(11). https://doi.org/10.1161/CIRCHEARTFAILURE.117.004373