title: Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism.
abstract: BACKGROUND
  Standard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio (INR) between 2.0 and 3.0. However, for long-term management, no therapeutic agent has shown an acceptable benefit-to-risk ratio.
  
  
  METHODS
  Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5 to 2.0). Participants were followed for recurrent venous thromboembolism, major hemorrhage, and death.
  
  
  RESULTS
  The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of 255 patients assigned to low-intensity warfarin (2.6 per 100 person-years), a risk reduction of 64 percent (hazard ratio, 0.36 [95 percent confidence interval, 0.19 to 0.67]; P<0.001). Risk reductions were similar for all subgroups, including those with and those without inherited thrombophilia. Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin (P=0.25). Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died (P=0.26). Low-intensity warfarin was thus associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism, major hemorrhage, or death. According to per-protocol and as-treated analyses, the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent.
  
  
  CONCLUSIONS
  Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism.
authors.affiliation: Center for Cardiovascular Disease Prevention and the Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston 02215, USA. pridker@partners.org
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.forename: Ellie
authors.initials: E
authors.lastname: Danielson
authors.forename: Yves
authors.initials: Y
authors.lastname: Rosenberg
authors.forename: Charles S
authors.initials: CS
authors.lastname: Eby
authors.forename: Steven R
authors.initials: SR
authors.lastname: Deitcher
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: Stephan
authors.initials: S
authors.lastname: Moll
authors.forename: Craig M
authors.initials: CM
authors.lastname: Kessler
authors.forename: C Gregory
authors.initials: CG
authors.lastname: Elliott
authors.forename: Rolf
authors.initials: R
authors.lastname: Paulson
authors.forename: Turnly
authors.initials: T
authors.lastname: Wong
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Bauer
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Schwartz
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Miletich
authors.forename: Henri
authors.initials: H
authors.lastname: Bounameaux
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000401:mortality / Q000517:prevention & control; D012306:Risk; D055502:Secondary Prevention; D020521:Stroke / Q000401:mortality; D013923:Thromboembolism / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin