title: Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism.
abstract: BACKGROUND
  Warfarin is very effective in preventing recurrent venous thromboembolism but is also associated with a substantial risk of bleeding. After three months of conventional warfarin therapy, a lower dose of anticoagulant medication may result in less bleeding and still prevent recurrent venous thromboembolism.
  
  
  METHODS
  We conducted a randomized, double-blind study, in which 738 patients who had completed three or more months of warfarin therapy for unprovoked venous thromboembolism were randomly assigned to continue warfarin therapy with a target international normalized ratio (INR) of 2.0 to 3.0 (conventional intensity) or a target INR of 1.5 to 1.9 (low intensity). Patients were followed for an average of 2.4 years.
  
  
  RESULTS
  Of 369 patients assigned to low-intensity therapy, 16 had recurrent venous thromboembolism (1.9 per 100 person-years), as compared with 6 of 369 assigned to conventional-intensity therapy (0.7 per 100 person-years; hazard ratio, 2.8; 95 percent confidence interval, 1.1 to 7.0). A major bleeding episode occurred in nine patients assigned to low-intensity therapy (1.1 events per 100 person-years) and eight patients assigned to conventional-intensity therapy (0.9 event per 100 person-years; hazard ratio, 1.2; 95 percent confidence interval, 0.4 to 3.0). There was no significant difference in the frequency of overall bleeding between the two groups (hazard ratio, 1.3; 95 percent confidence interval, 0.8 to 2.1).
  
  
  CONCLUSIONS
  Conventional-intensity warfarin therapy is more effective than low-intensity warfarin therapy for the long-term prevention of recurrent venous thromboembolism. The low-intensity warfarin regimen does not reduce the risk of clinically important bleeding.
authors.affiliation: McMaster University, Hamilton, Ont.
authors.forename: Clive
authors.initials: C
authors.lastname: Kearon
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ginsberg
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kovacs
authors.forename: David R
authors.initials: DR
authors.lastname: Anderson
authors.forename: Philip
authors.initials: P
authors.lastname: Wells
authors.forename: Jim A
authors.initials: JA
authors.lastname: Julian
authors.forename: Betsy
authors.initials: B
authors.lastname: MacKinnon
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
authors.forename: Mark A
authors.initials: MA
authors.lastname: Crowther
authors.forename: Sean
authors.initials: S
authors.lastname: Dolan
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Turpie
authors.forename: William
authors.initials: W
authors.lastname: Geerts
authors.forename: Susan
authors.initials: S
authors.lastname: Solymoss
authors.forename: Paul
authors.initials: P
authors.lastname: van Nguyen
authors.forename: Christine
authors.initials: C
authors.lastname: Demers
authors.forename: Susan R
authors.initials: SR
authors.lastname: Kahn
authors.forename: Jeannine
authors.initials: J
authors.lastname: Kassis
authors.forename: Marc
authors.initials: M
authors.lastname: Rodger
authors.forename: Julie
authors.initials: J
authors.lastname: Hambleton
authors.forename: Michael
authors.initials: M
authors.lastname: Gent
mesh_terms: D000367:Age Factors; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000401:mortality / Q000517:prevention & control*; D012307:Risk Factors; D055502:Secondary Prevention; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D014859:Warfarin