title: Levosimendan meta-analyses: Is there a pattern in the effect on mortality?
abstract: BACKGROUND
  Levosimendan is an inodilator developed for treatment of acute heart failure and other cardiac conditions where the use of an inodilator is considered appropriate. Levosimendan has been studied in different therapeutic settings including acutely decompensated chronic heart failure, advanced heart failure, right ventricular failure, cardiogenic shock, septic shock, and cardiac and non-cardiac surgery. This variety of data has been re-analysed in 25 meta-analyses from 15 different international research groups, based on different rationales to select the studies included.
  
  
  METHODS
  We here review all previously published meta-analyses on levosimendan to determine any common denominators for its effects on patient mortality. In addition, we also perform a comparative meta-analysis of the six phase II and III randomized double-blind trials which were taken into consideration by the regulatory authorities for the purpose of introducing levosimendan into the market.
  
  
  RESULTS
  Irrespective of clinical setting or comparator, all meta-analyses consistently show benefits for levosimendan, with lower relative risk (or odds ratio) for patient mortality. In 3/25 of the meta-analyses these beneficial trends did not reach statistical significance, while in 22/25 significance was reached. The relative risk is consistent overall, and very similar to that obtained in our own meta-analysis that considered only the 'regulatory' studies.
  
  
  CONCLUSIONS
  The existing meta-analyses, now based on a population of over 6000 patients, provide the general message of significant benefits for levosimendan in terms of patient mortality. The weight of evidence is now clearly in favour of usefulness/efficacy of levosimendan, with data from multiple randomized trials and meta-analyses.
authors.affiliation: Critical Care Proprietary Products, Orion Pharma, Espoo, Finland. Electronic address: piero.pollesello@orionpharma.com.
authors.forename: P
authors.initials: P
authors.lastname: Pollesello
authors.affiliation: Second Department of Cardiology and Heart Failure Unit, University of Athens Medical School, Attikon University Hospital, Athens, Greece.
authors.forename: J
authors.initials: J
authors.lastname: Parissis
authors.affiliation: Critical Care Proprietary Products, Orion Pharma, Espoo, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Kivikko
authors.affiliation: Emergency Medicine, Helsinki University, Helsinki University Hospital, Helsinki, Finland.
authors.forename: V-P
authors.initials: VP
authors.lastname: Harjola
mesh_terms: D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002423:Cause of Death; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004311:Double-Blind Method; D006331:Heart Diseases / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D015201:Meta-Analysis as Topic; D011724:Pyridazines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000077464:Simendan; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan
keywords: Acute cardiac care; Cardiac surgery; Heart failure; Inodilator; Meta-analysis; Mortality