title: Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies.
abstract: OBJECTIVE
  Catecholaminergic inotropes have a place in the management of low output syndrome and decompensated heart failure but their effect on mortality is debated. Levosimendan is a calcium sensitizer that enhances myocardial contractility without increasing myocardial oxygen use. A meta-analysis was conducted to determine the impact of levosimendan on mortality and hospital stay.
  
  
  METHODS
  BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials were searched for pertinent studies. International experts and the manufacturer were contacted.
  
  
  METHODS
  Articles were assessed by four trained investigators, with divergences resolved by consensus. Inclusion criteria were random allocation to treatment and comparison of levosimendan vs. control. There were no restrictions on dose or time of levosimendan administration or on language. Exclusion criteria were: duplicate publications, nonadult studies, oral administration of levosimendan, and no data on main outcomes.
  
  
  METHODS
  Study end points, main outcomes, study design, population, clinical setting, levosimendan dosage, and treatment duration were extracted.
  
  
  RESULTS
  Data from 5,480 patients in 45 randomized clinical trials were analyzed. The overall mortality rate was 17.4% (507 of 2,915) among levosimendan-treated patients and 23.3% (598 of 2,565) in the control group (risk ratio 0.80 [0.72; 0.89], p for effect <.001, number needed to treat = 17 with 45 studies included). Reduction in mortality was confirmed in studies with placebo (risk ratio 0.82 [0.69; 0.97], p = .02) or dobutamine (risk ratio 0.68 [0.52-0.88]; p = .003) as comparator and in studies performed in cardiac surgery (risk ratio 0.52 [0.35; 0.76] p = .001) or cardiology (risk ratio 0.75 [0.63; 0.91], p = .003) settings. Length of hospital stay was reduced in the levosimendan group (weighted mean difference = -1.31 [-1.95; -0.31], p for effect = .007, with 17 studies included). A trend toward a higher percentage of patients experiencing hypotension was noted in levosimendan vs. control (risk ratio 1.39 [0.97-1.94], p = .053).
  
  
  CONCLUSIONS
  Levosimendan might reduce mortality in cardiac surgery and cardiology settings of adult patients.
authors.affiliation: Department of Anesthesia and Intensive Care, Università Vita-Salute San Raffaele, Milano, Italy. landoni.giovanni@hsr.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Landoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi-Zoccai
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Greco
authors.forename: Teresa
authors.initials: T
authors.lastname: Greco
authors.forename: Elena
authors.initials: E
authors.lastname: Bignami
authors.forename: Andrea
authors.initials: A
authors.lastname: Morelli
authors.forename: Fabio
authors.initials: F
authors.lastname: Guarracino
authors.forename: Alberto
authors.initials: A
authors.lastname: Zangrillo
mesh_terms: D006348:Cardiac Surgical Procedures / Q000401:mortality; D003422:Critical Care / Q000379:methods; D016638:Critical Illness / Q000401:mortality; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000401:mortality; D017052:Hospital Mortality / Q000639:trends*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D011379:Prognosis; D011724:Pyridazines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D000077464:Simendan; D016896:Treatment Outcome
chemical_list: D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan