title: Comparative safety of interleukin-1 blockade with anakinra in patients with ST-segment elevation acute myocardial infarction (from the VCU-ART and VCU-ART2 pilot studies).
abstract: Two pilot studies of interleukin-1 (IL-1) blockade in ST-segment elevation myocardial infarction (STEMI) showed blunted acute inflammatory response and overall favorable outcomes at 3 months follow-up. We hereby present a patient-level pooled analysis with extended follow-up of 40 patients with clinically stable STEMI randomized to anakinra, a recombinant IL-1 receptor antagonist, 100 mg/day for 14 days or placebo in a double-blinded fashion. End points included death, cardiac death, recurrent acute myocardial infarction (AMI), stroke, unstable angina, and symptomatic heart failure. Median follow-up was 28 (interquartile range 3 to 38) months. Sixteen patients (40%) had a total of 22 adverse cardiovascular events: 1 cardiac death, 4 recurrent AMI, 5 episodes of unstable angina pectoris requiring hospitalization and/or urgent revascularization, and 11 new diagnoses of heart failure. Treatment with anakinra was associated with a hazard ratio of 1.08 (95% confidence interval 0.31 to 3.74, p = 0.90) for the combined end point of death, recurrent AMI, unstable angina pectoris, or stroke and a hazard ratio of 0.16 (95% confidence interval 0.03 to 0.76, p = 0.008) for death or heart failure. In conclusion, IL-1 blockade with anakinra for 2 weeks appears, therefore, to have a neutral effect on recurrent ischemic events, whereas it may prevent new-onset heart failure long term after STEMI.
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia. Electronic address: aabbate@vcu.edu.
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Michael Christopher
authors.initials: MC
authors.lastname: Kontos
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Nayef Antar
authors.initials: NA
authors.lastname: Abouzaki
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Ryan David
authors.initials: RD
authors.lastname: Melchior
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Thomas
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Benjamin Wallace
authors.initials: BW
authors.lastname: Van Tassell
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Claudia
authors.initials: C
authors.lastname: Oddi
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Carbone
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Cory Ross
authors.initials: CR
authors.lastname: Trankle
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Charlotte Susan
authors.initials: CS
authors.lastname: Roberts
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: George Herman
authors.initials: GH
authors.lastname: Mueller
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Michael Lucas
authors.initials: ML
authors.lastname: Gambill
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Sanah
authors.initials: S
authors.lastname: Christopher
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Roshanak
authors.initials: R
authors.lastname: Markley
authors.affiliation: VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: George Wayne
authors.initials: GW
authors.lastname: Vetrovec
authors.affiliation: Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Charles Anthony
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi-Zoccai
mesh_terms: D000368:Aged; D000789:Angina, Unstable; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000276:immunology; D010865:Pilot Projects; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1