title: Systematic review: benefits and harms of in-hospital use of recombinant factor VIIa for off-label indications.
abstract: BACKGROUND
  Recombinant factor VIIa (rFVIIa), a hemostatic agent approved for hemophilia, is increasingly used for off-label indications.
  
  
  OBJECTIVE
  To evaluate the benefits and harms of rFVIIa use for 5 off-label, in-hospital indications: intracranial hemorrhage, cardiac surgery, trauma, liver transplantation, and prostatectomy.
  
  
  METHODS
  Ten databases (including PubMed, EMBASE, and the Cochrane Library) queried from inception through December 2010. Articles published in English were analyzed.
  
  
  METHODS
  Two reviewers independently screened titles and abstracts to identify clinical use of rFVIIa for the selected indications and identified all randomized, controlled trials (RCTs) and observational studies for full-text review.
  
  
  METHODS
  Two reviewers independently assessed study characteristics and rated study quality and indication-wide strength of evidence.
  
  
  RESULTS
  16 RCTs, 26 comparative observational studies, and 22 noncomparative observational studies met inclusion criteria. Identified comparators were limited to placebo (RCTs) or usual care (observational studies). For intracranial hemorrhage, mortality was not improved with rFVIIa use across a range of doses. Arterial thromboembolism was increased with medium-dose rFVIIa use (risk difference [RD], 0.03 [95% CI, 0.01 to 0.06]) and high-dose rFVIIa use (RD, 0.06 [CI, 0.01 to 0.11]). For adult cardiac surgery, there was no mortality difference, but there was an increased risk for thromboembolism (RD, 0.05 [CI, 0.01 to 0.10]) with rFVIIa. For body trauma, there were no differences in mortality or thromboembolism, but there was a reduced risk for the acute respiratory distress syndrome (RD, -0.05 [CI, -0.02 to -0.08]). Mortality was higher in observational studies than in RCTs.
  
  
  CONCLUSIONS
  The amount and strength of evidence were low for most outcomes and indications. Publication bias could not be excluded.
  
  
  CONCLUSIONS
  Limited available evidence for 5 off-label indications suggests no mortality reduction with rFVIIa use. For some indications, it increases thromboembolism.
authors.affiliation: Stanford University, Stanford, CA, USA. vyank@stanford.edu
authors.forename: Veronica
authors.initials: V
authors.lastname: Yank
authors.forename: C Vaughan
authors.initials: CV
authors.lastname: Tuohy
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Logan
authors.forename: Dena M
authors.initials: DM
authors.lastname: Bravata
authors.forename: Kristan
authors.initials: K
authors.lastname: Staudenmayer
authors.forename: Robin
authors.initials: R
authors.lastname: Eisenhut
authors.forename: Vandana
authors.initials: V
authors.lastname: Sundaram
authors.forename: Donal
authors.initials: D
authors.lastname: McMahon
authors.forename: Ingram
authors.initials: I
authors.lastname: Olkin
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: McDonald
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Owens
authors.forename: Randall S
authors.initials: RS
authors.lastname: Stafford
mesh_terms: D013504:Cardiovascular Surgical Procedures / Q000009:adverse effects; D002423:Cause of Death; D057186:Comparative Effectiveness Research; D015942:Factor VIIa / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006490:Hemostatics / Q000009:adverse effects / Q000627:therapeutic use*; D006753:Hospital Records; D006761:Hospitals; D006801:Humans; D020300:Intracranial Hemorrhages / Q000188:drug therapy; D016031:Liver Transplantation / Q000009:adverse effects; D056687:Off-Label Use; D019106:Postoperative Hemorrhage / Q000188:drug therapy; D011468:Prostatectomy / Q000009:adverse effects; D012107:Research Design; D012307:Risk Factors; D013923:Thromboembolism / Q000209:etiology; D014481:United States; D014947:Wounds and Injuries / Q000150:complications
chemical_list: D006490:Hemostatics; D015942:Factor VIIa