title: Repeated or intermittent levosimendan treatment in advanced heart failure: An updated meta-analysis.
abstract: BACKGROUND
  Advanced heart failure is a malignant disease characterized by a debilitating late course, with increasingly frequent hospitalisations and high rate of mortality. Levosimendan, an inodilator developed for the treatment of acutely decompensated chronic heart failure, has been recently proposed also as a repetitive treatment of advanced heart failure. Several studies on the use of levosimendan in this settings report mortality data. Independent meta-analyses on the effect on mortality of repetitive or intermittent levosimendan administration in advanced heart failure has been published but were criticized in regard to the selection of the studies. Meanwhile new data became available. We therefore updated the selection of studies and re-analyzed all the available data.
  
  
  RESULTS
  Data from seven randomized trial and a total of 438 adult patients using intermittent levosimendan in a cardiological setting were included in the present analysis. The average follow-up period was 8±3.8 months. The use of levosimendan was associated with a significant reduction in mortality at the longest follow-up available [41 of 257 (16%) in the levosimendan group vs. 39 of 181 (21.5%) in the control arm, OR=0.54 (95% CI 0.32-0.91), p for effect=0.02, p for heterogeneity=0.64, I2=0%].
  
  
  CONCLUSIONS
  The updated results suggest that repetitive or intermittent levosimendan administration in advanced heart failure is associated with a significant reduction in mortality at the longest follow-up available. There is therefore a strong rationale for a randomized clinical trial with adequate power on mortality.
authors.affiliation: IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Silvetti
authors.affiliation: Helsinki University Central Hospital, Helsinki, Finland. Electronic address: markku.nieminen@hus.fi.
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
mesh_terms: D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D006333:Heart Failure / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage*; D011724:Pyridazines / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D000077464:Simendan; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan
keywords: Advanced heart failure; Intermittent; Levosimendan; Meta-analysis; Repetitive; Vasoactive treatment