title: Interleukin-1 Blockade in Acute Decompensated Heart Failure: A Randomized, Double-Blinded, Placebo-Controlled Pilot Study.
abstract: BACKGROUND
  Heart failure is an inflammatory disease. Patients with acute decompensated heart failure (ADHF) exhibit significant inflammatory activity on admission. We hypothesized that Interleukin-1 blockade, with anakinra (Kineret, Swedish Orphan Biovitrum), would quench the acute inflammatory response in patients with ADHF.
  
  
  METHODS
  We randomized 30 patients with ADHF, reduced left ventricular ejection fraction (<40%), and elevated C reactive protein (CRP) levels (≥5 mg/L) to either anakinra 100 mg twice daily for 3 days followed by once daily for 11 days or matching placebo, in a 1:1 double blinded fashion. We measured daily CRP plasma levels using a high-sensitivity assay during hospitalization and then again at 14 days and evaluated the area-under-the-curve and interval changes (delta).
  
  
  RESULTS
  Treatment with anakinra was well tolerated. At 72 hours, anakinra reduced CRP by 61% versus baseline, compared with a 6% reduction among patients receiving placebo (P = 0.004 anakinra vs. placebo).
  
  
  CONCLUSIONS
  Interleukin-1 blockade with anakinra reduces the systemic inflammatory response in patients with ADHF. Further studies are warranted to determine whether this anti-inflammatory effect translates into improved clinical outcomes.
authors.affiliation: *Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA;†Pauley Heart Center, School of Medicine, Virginia Commonwealth University, Richmond, VA;‡Division of Infectious Diseases, School of Medicine, University of Colorado, Denver, CO;§Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; and‖Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Van Tassell
authors.forename: Nayef A
authors.initials: NA
authors.lastname: Abouzaki
authors.forename: Claudia
authors.initials: C
authors.lastname: Oddi Erdle
authors.forename: Salvatore
authors.initials: S
authors.lastname: Carbone
authors.forename: Cory R
authors.initials: CR
authors.lastname: Trankle
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Melchior
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Turlington
authors.forename: Clinton J
authors.initials: CJ
authors.lastname: Thurber
authors.forename: Sanah
authors.initials: S
authors.lastname: Christopher
authors.forename: Dave L
authors.initials: DL
authors.lastname: Dixon
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Fronk
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Thomas
authors.forename: Scott W
authors.initials: SW
authors.lastname: Rose
authors.forename: Leo F
authors.initials: LF
authors.lastname: Buckley
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi-Zoccai
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
mesh_terms: D000208:Acute Disease; D015415:Biomarkers; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1