title: Off-label use of recombinant activated factor VII in surgical and non-surgical patients at 16 Canadian hospitals from 2007 to 2010 (Canadian Registry Report).
abstract: OBJECTIVE
  Recombinant activated factor VII (rFVIIa) is a pro-hemostatic drug that is approved for treatment of bleeding in hemophilia patients, but it is frequently used off-label in non-hemophiliacs. The purpose of this study was to determine if the off-label use of rFVIIa is expanding and whether this poses a net harm to patients.
  
  
  METHODS
  For this historical cohort study, data were collected on all non-hemophilia patients who received rFVIIa from 2007 to 2010 at 16 Canadian centres, and the pattern of use was examined. Logistic regression was used to determine the prognostic importance of severity of bleeding and the presence of an rFVIIa dose-effect relationship with major adverse events.
  
  
  RESULTS
  One thousand three hundred seventy-eight patients received rFVIIa off-label, and 987 (72%) of these patients underwent cardiac surgery. The median [interquartile range] dose was 57 [36-85] µg·kg(-1). Usage increased from 2007 to 2008 (n = 341 and 380, respectively) but decreased in 2009 and 2010 (n = 350 and 307, respectively). Dose of rFVIIa and bleeding severity were associated with measured adverse events (P < 0.05). After adjusting for bleeding severity, dose was not associated with any of the adverse events.
  
  
  CONCLUSIONS
  The off-label use of rFVIIa in Canada remains stable. Since severity of bleeding is prognostically important, the benefits of rapidly gaining control of bleeding that is non-responsive to conventional therapies may at times warrant the use of potent hemostatic drugs with established risk profiles, such as rFVIIa.
authors.affiliation: Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, 200 Elizabeth Street, 3EN, Toronto, ON, M5G 2C4, Canada, keyvan.karkouti@uhn.ca.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Karkouti
authors.forename: Ramiro
authors.initials: R
authors.lastname: Arellano
authors.forename: Tim
authors.initials: T
authors.lastname: Aye
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Dupuis
authors.forename: Blaine
authors.initials: B
authors.lastname: Kent
authors.forename: Trevor W R
authors.initials: TW
authors.lastname: Lee
authors.forename: Yulia
authors.initials: Y
authors.lastname: Lin
authors.forename: Fiona
authors.initials: F
authors.lastname: Ralley
authors.forename: Charles
authors.initials: C
authors.lastname: MacAdams
authors.forename: C David
authors.initials: CD
authors.lastname: Mazer
authors.forename: Brian
authors.initials: B
authors.lastname: Muirhead
authors.forename: Michel R
authors.initials: MR
authors.lastname: Rheault
authors.forename: Antoine
authors.initials: A
authors.lastname: Rochon
authors.forename: Summer
authors.initials: S
authors.lastname: Syed
authors.forename: Terrence
authors.initials: T
authors.lastname: Waters
authors.forename: Bill
authors.initials: B
authors.lastname: Wong
mesh_terms: D000368:Aged; D002170:Canada; D015331:Cohort Studies; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy*; D006490:Hemostatics / Q000627:therapeutic use; D006761:Hospitals / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D056687:Off-Label Use / Q000706:statistics & numerical data*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012042:Registries
chemical_list: D006490:Hemostatics; D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa