title: Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure.
abstract: BACKGROUND
  This study evaluated the efficacy and safety of levosimendan, a positive inotropic drug with vasodilator effects, given intravenously to patients with acutely decompensated heart failure (ADHF).
  
  
  METHODS
  We performed 2 sequential trials, the first to develop a new measure of efficacy in 100 patients, and the second to use this measure to evaluate levosimendan in an additional 600 patients. Patients admitted with ADHF received placebo or intravenous levosimendan for 24 h in addition to standard treatment. The primary endpoint was a composite that evaluated changes in clinical status during the first 5 days after randomization.
  
  
  RESULTS
  In the 600-patient trial, more levosimendan than placebo patients (58 vs. 44) were improved at all 3 pre-specified time points (6 h, 24 h, and 5 days), whereas fewer levosimendan patients (58 vs. 82) experienced clinical worsening (p = 0.015 for the difference between the groups). These differences were apparent, despite more frequent intensification of adjunctive therapy in the placebo group (79 vs. 45 patients). Improvements in patient self-assessment and declines in B-type natriuretic peptide levels with levosimendan persisted for 5 days and were associated with reduced length of stay (p = 0.009). Similar findings were present in the 100-patient pilot trial. Levosimendan was associated with more frequent hypotension and cardiac arrhythmias during the infusion period and a numerically higher risk of death across the 2 trials (49 of 350 on a regimen of levosimendan vs. 40 of 350 on a regimen of placebo at 90 days, p = 0.29).
  
  
  CONCLUSIONS
  In patients with ADHF, intravenous levosimendan provided rapid and durable symptomatic relief. As dosed in this trial, levosimendan was associated with an increased risk of adverse cardiovascular events. (Evaluation of Intravenous Levosimendan Efficacy in the Short Term Treatment of Decompensated Chronic Heart Failure; NCT00048425).
authors.affiliation: Department of Clinical Sciences, University of Texas Medical Center at Dallas, Dallas, Texas. Electronic address: Milton.Packer@UTSouthwestern.edu.
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Wilson
authors.initials: W
authors.lastname: Colucci
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Fisher
authors.affiliation: Department of Medicine, University of California at San Francisco and VA Medical Center, San Francisco, California.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Massie
authors.affiliation: Department of Medicine, University of California at San Francisco and VA Medical Center, San Francisco, California.
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
authors.affiliation: Department of Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: James
authors.initials: J
authors.lastname: Young
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Padley
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois.
authors.forename: Roopal
authors.initials: R
authors.lastname: Thakkar
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois.
authors.forename: Leticia
authors.initials: L
authors.lastname: Delgado-Herrera
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Salon
authors.affiliation: Orion Corporation, Orion Pharma, Espoo, Finland.
authors.forename: Chris
authors.initials: C
authors.lastname: Garratt
authors.affiliation: Abbott Laboratories, Abbott Park, Illinois.
authors.forename: Bidan
authors.initials: B
authors.lastname: Huang
authors.affiliation: Orion Corporation, Orion Pharma, Espoo, Finland.
authors.forename: Toni
authors.initials: T
authors.lastname: Sarapohja
mesh_terms: D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011724:Pyridazines / Q000627:therapeutic use*; D000077464:Simendan
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan
keywords: heart failure; inotropic agents; trials