title: Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism.
abstract: BACKGROUND
  When unfractionated heparin is used to treat acute venous thromboembolism, it is usually administered by intravenous infusion with coagulation monitoring, which requires hospitalization. However, subcutaneous administration of fixed-dose, weight-adjusted, unfractionated heparin may be suitable for inpatient and outpatient treatment of venous thromboembolism.
  
  
  OBJECTIVE
  To determine if fixed-dose, weight-adjusted, subcutaneous unfractionated heparin is as effective and safe as low-molecular-weight heparin for treatment of venous thromboembolism.
  
  
  METHODS
  Randomized, open-label, adjudicator-blinded, noninferiority trial of 708 patients aged 18 years or older with acute venous thromboembolism from 6 university-affiliated clinical centers in Canada and New Zealand conducted from September 1998 through February 2004. Of the randomized patients, 11 were subsequently excluded from the analysis of efficacy and 8 from the analysis of safety.
  
  
  METHODS
  Unfractionated heparin was administered subcutaneously as an initial dose of 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours (n = 345). Low-molecular-weight heparin (dalteparin or enoxaparin) was administered subcutaneously at a dose of 100 IU/kg every 12 hours (n = 352). Both treatments could be administered out of hospital and both were overlapped with 3 months of warfarin therapy.
  
  
  METHODS
  Recurrent venous thromboembolism within 3 months and major bleeding within 10 days of randomization.
  
  
  RESULTS
  Recurrent venous thromboembolism occurred in 13 patients in the unfractionated heparin group (3.8%) compared with 12 patients in the low-molecular-weight heparin group (3.4%; absolute difference, 0.4%; 95% confidence interval, -2.6% to 3.3%). Major bleeding during the first 10 days of treatment occurred in 4 patients in the unfractionated heparin group (1.1%) compared with 5 patients in the low-molecular-weight heparin group (1.4%; absolute difference, -0.3%; 95% confidence interval, -2.3% to 1.7%). Treatment was administered entirely out of hospital in 72% of the unfractionated heparin group and 68% of the low-molecular-weight heparin group.
  
  
  CONCLUSIONS
  Fixed-dose subcutaneous unfractionated heparin is as effective and safe as low-molecular-weight heparin in patients with acute venous thromboembolism and is suitable for outpatient treatment.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00182403.
authors.affiliation: McMaster University and the Henderson Research Centre, Hamilton, Ontario.
authors.forename: Clive
authors.initials: C
authors.lastname: Kearon
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ginsberg
authors.forename: Jim A
authors.initials: JA
authors.lastname: Julian
authors.forename: James
authors.initials: J
authors.lastname: Douketis
authors.forename: Susan
authors.initials: S
authors.lastname: Solymoss
authors.forename: Paul
authors.initials: P
authors.lastname: Ockelford
authors.forename: Sharon
authors.initials: S
authors.lastname: Jackson
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Turpie
authors.forename: Betsy
authors.initials: B
authors.lastname: MacKinnon
authors.forename: Jack
authors.initials: J
authors.lastname: Hirsh
authors.forename: Michael
authors.initials: M
authors.lastname: Gent
mesh_terms: D000368:Aged; D000553:Ambulatory Care; D000925:Anticoagulants / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006493:Heparin / Q000008:administration & dosage*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011655:Pulmonary Embolism / Q000188:drug therapy*; D020246:Venous Thrombosis / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin