Off-label use of recombinant factor VIIa in U.S. hospitals: analysis of hospital records

Ann Intern Med. 2011 Apr 19;154(8):516-22. doi: 10.7326/0003-4819-154-8-201104190-00002.

Abstract

Background: Recombinant factor VIIa (rFVIIa) is approved for treatment of bleeding in patients who have hemophilia with inhibitors but has been applied to a wide range of off-label indications.

Objective: To estimate patterns of off-label rFVIIa use in U.S. hospitals.

Design: Retrospective database analysis.

Setting: Data were extracted from the Premier Perspectives database (Premier, Charlotte, North Carolina), which contains discharge records from a sample of academic and nonacademic U.S. hospitals.

Patients: 12 644 hospitalizations for patients who received rFVIIa during a hospital stay.

Measurements: Hospital diagnoses and patient dispositions from 1 January 2000 to 31 December 2008. Statistical weights for each hospital were used to provide national estimates of rFVIIa use.

Results: From 2000 to 2008, off-label use of rFVIIa in hospitals increased more than 140-fold, such that in 2008, 97% (95% CI, 96% to 98%) of 18 311 in-hospital uses were off-label. In contrast, in-hospital use for hemophilia increased less than 4-fold and accounted for 2.7% (CI, 1.9% to 3.5%) of use in 2008. Adult and pediatric cardiovascular surgery (29% [CI, 21% to 33%]), body and brain trauma (29% [CI, 19% to 38%]), and intracranial hemorrhage (11% [CI, 7.7% to 14%]) were the most common indications for rFVIIa use. Across all indications, in-hospital mortality was 27% (CI, 19% to 34%) and 43% (CI, 26% to 59%) of patients were discharged to home.

Limitation: Accuracy and completeness of the discharge diagnoses and patient medication records in the database sample cannot be verified.

Conclusion: Off-label use of rFVIIa in the hospital setting far exceeds use for approved indications. These patterns raise concern about the application of rFVIIa to conditions for which strong supporting evidence is lacking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Cardiovascular Surgical Procedures / adverse effects
  • Child
  • Child, Preschool
  • Factor VIIa / therapeutic use*
  • Hemophilia A / drug therapy
  • Hemorrhage / drug therapy*
  • Hemorrhage / etiology
  • Hemostatics / therapeutic use*
  • Hospital Mortality
  • Hospital Records
  • Hospitals*
  • Humans
  • Intracranial Hemorrhages / drug therapy
  • Liver Diseases / complications
  • Liver Diseases / surgery
  • Middle Aged
  • Off-Label Use*
  • Retrospective Studies
  • United States
  • Wounds and Injuries / complications
  • Young Adult

Substances

  • Hemostatics
  • Factor VIIa