title: Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial.
abstract: BACKGROUND
  Low-dose oral vitamin K decreases the international normalized ratio (INR) in overanticoagulated patients who receive warfarin therapy. Its effects on bleeding events are uncertain.
  
  
  OBJECTIVE
  To see whether low-dose oral vitamin K reduces bleeding events over 90 days in patients with warfarin-associated coagulopathy.
  
  
  METHODS
  Multicenter, randomized, placebo-controlled trial. Randomization was computer-generated, and participants were allocated to trial groups by using sequentially numbered study drug containers. Patients, caregivers, and those who assessed outcomes were blinded to treatment assignment.
  
  
  METHODS
  14 anticoagulant therapy clinics in Canada, the United States, and Italy.
  
  
  METHODS
  Nonbleeding patients with INR values of 4.5 to 10.0.
  
  
  METHODS
  Oral vitamin K, 1.25 mg (355 patients randomly assigned; 347 analyzed), or matching placebo (369 patients randomly assigned; 365 analyzed).
  
  
  METHODS
  Bleeding events (primary outcome), thromboembolism, and death (secondary outcomes).
  
  
  RESULTS
  56 patients (15.8%) in the vitamin K group and 60 patients (16.3%) in the placebo group had at least 1 bleeding complication (absolute difference, -0.5 percentage point [95% CI, -6.1 to 5.1 percentage points]); major bleeding events occurred in 9 patients (2.5%) in the vitamin K group and 4 patients (1.1%) in the placebo group (absolute difference, 1.5 percentage points [CI, -0.8 to 3.7 percentage points]). Thromboembolism occurred in 4 patients (1.1%) in the vitamin K group and 3 patients (0.8%) in the placebo group (absolute difference, 0.3 percentage point [CI, -1.4 to 2.0 percentage points]). Other adverse effects were not assessed. The day after treatment, the INR had decreased by a mean of 1.4 in the placebo group and 2.8 in the vitamin K group (P < 0.001).
  
  
  CONCLUSIONS
  Patients who were actively bleeding were not included, and warfarin dosing after enrollment was not mandated or followed.
  
  
  CONCLUSIONS
  Low-dose oral vitamin K did not reduce bleeding in warfarin recipients with INRs of 4.5 to 10.0.
  
  
  BACKGROUND
  Canadian Institutes of Health Research and Italian Ministry of Universities and Research.
authors.affiliation: McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Crowther
authors.forename: Walter
authors.initials: W
authors.lastname: Ageno
authors.forename: David
authors.initials: D
authors.lastname: Garcia
authors.forename: Luqi
authors.initials: L
authors.lastname: Wang
authors.forename: Dan M
authors.initials: DM
authors.lastname: Witt
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Clark
authors.forename: Mark D
authors.initials: MD
authors.lastname: Blostein
authors.forename: Susan R
authors.initials: SR
authors.lastname: Kahn
authors.forename: Sara K
authors.initials: SK
authors.lastname: Vesely
authors.forename: Sam
authors.initials: S
authors.lastname: Schulman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kovacs
authors.forename: Marc A
authors.initials: MA
authors.lastname: Rodger
authors.forename: Phillip
authors.initials: P
authors.lastname: Wells
authors.forename: David
authors.initials: D
authors.lastname: Anderson
authors.forename: Jeffery
authors.initials: J
authors.lastname: Ginsberg
authors.forename: Rita
authors.initials: R
authors.lastname: Selby
authors.forename: Sergio
authors.initials: S
authors.lastname: Siragusa
authors.forename: Mauro
authors.initials: M
authors.lastname: Silingardi
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Dowd
authors.forename: Clive
authors.initials: C
authors.lastname: Kearon
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013923:Thromboembolism / Q000517:prevention & control; D016896:Treatment Outcome; D014812:Vitamin K / Q000008:administration & dosage*; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D010919:Placebos; D014812:Vitamin K; D014859:Warfarin