title: Levosimendan for the treatment of acute severe heart failure: a meta-analysis of randomised controlled trials.
abstract: BACKGROUND
  The objective of this study was to critically review the literature to evaluate whether levosimendan compared to standard therapy, in patients with acute severe heart failure, is associated with improved clinical outcomes.
  
  
  METHODS
  Medline, EMBASE, and the Cochrane central register of clinical trials were searched. We also searched clinical trials registries, bibliographies of included studies and review articles and contacted the manufacturers of levosimendan to identify unpublished studies. Randomised clinical trials comparing levosimendan to standard therapy or placebo, in adult patients with acute severe heart failure, reporting at least one outcome of interest were included. Data were extracted regarding the characteristics, methodological quality and clinical outcomes, and combined using a fixed-effect meta-analysis.
  
  
  RESULTS
  We identified 19 RCTs enrolling 3650 patients, only two studies fulfilled all of the validity criteria. There was a non-significant reduction in mortality with levosimendan compared with placebo (OR 0.83, 95%CI, 0.62-1.10, p=0.20). Levosimendan was associated with reduced mortality compared to dobutamine (OR 0.75, 95%CI, 0.61-0.92, p=0.005). Levosimendan was associated with improvements in haemodynamic parameters when compared to either placebo or dobutamine.
  
  
  CONCLUSIONS
  Levosimendan improved haemodynamic parameters when compared with placebo, without showing evidence of survival benefit. Levosimendan improved both haemodynamics and survival when compared with dobutamine.
authors.affiliation: Intensive Care Unit, Royal North Shore Hospital, Pacific Highway, St. Leonards, NSW, 2065, Australia. adelaney@med.usyd.edu.au
authors.forename: Anthony
authors.initials: A
authors.lastname: Delaney
authors.forename: Celia
authors.initials: C
authors.lastname: Bradford
authors.forename: John
authors.initials: J
authors.lastname: McCaffrey
authors.forename: Sean M
authors.initials: SM
authors.lastname: Bagshaw
authors.forename: Richard
authors.initials: R
authors.lastname: Lee
mesh_terms: D000208:Acute Disease; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D011724:Pyridazines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D000077464:Simendan
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan