TY - JOUR
T1 - Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure
T2 - Results From REDHART (Recently Decompensated Heart Failure Anakinra Response Trial)
AU - Van Tassell, Benjamin W.
AU - Canada, Justin
AU - Carbone, Salvatore
AU - Trankle, Cory
AU - Buckley, Leo
AU - Oddi Erdle, Claudia
AU - Abouzaki, Nayef A.
AU - Dixon, Dave
AU - Kadariya, Dinesh
AU - Christopher, Sanah
AU - Schatz, Aaron
AU - Regan, Jessica
AU - Viscusi, Michele
AU - Del Buono, Marco
AU - Melchior, Ryan
AU - Mankad, Pranav
AU - Lu, Juan
AU - Sculthorpe, Robin
AU - Biondi-Zoccai, Giuseppe
AU - Lesnefsky, Edward
AU - Arena, Ross
AU - Abbate, Antonio
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
KW - heart failure
KW - heart failure, systolic
KW - inflammation
KW - interleukin-1
KW - myocardial infarction
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UR - http://www.scopus.com/inward/citedby.url?scp=85038008239&partnerID=8YFLogxK
U2 - 10.1161/CIRCHEARTFAILURE.117.004373
DO - 10.1161/CIRCHEARTFAILURE.117.004373
M3 - Article
C2 - 29141858
AN - SCOPUS:85038008239
VL - 10
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
SN - 1941-3297
IS - 11
ER -