Anticoagulation: oral vitamin K controls a supratherapeutic INR better than placebo and leads to less bleeding

Clinical bottom line (level 1b)

  1. Patients on warfarin with an INR 4.5 to 10.0 who received 1 mg vitamin K orally compared with placebo were more likely to have an INR 1.8 to 3.2 the next day (NNT = 3 at 24 hours) .
  2. Patients given vitamin K were less likely to have a bleeding episode (NNT = 7 at 3 months) .
Crowther et al: Lancet 2000; 356 : 1551-1553
Expires October 2003

The study

Double-blinded unconcealed randomised trial without intention-to-treat
Setting: 5 acute hospitals, Canada

92 patients (aged mean 64, 53% female) on warfarin with INR 4.5 to 10.0

Excluded if
  • known bleeding diathesis or thrombolytic treatment within 48 hours
  • inability to take oral medication
  • platelet count < 50 x 10 9 /l
  • INR determined more than 12 hours before screening
  • predicted life expectancy less than 10 days
  • indication for immediate normalisation of INR (e.g. active bleeding or need for surgery)
  • severe liver disease
  • major bleeding within previous month
  • known allergy to vitamin K
  • therapeutic range not 2.0 to 3.0

    Control Group: (n = 46, 44 analysed): placebo
    Experimental Group: (n = 46, 45 analysed): vitamin K 1mg orally
    Patients had warfarin medication stopped - this was restarted at the discretion of the treating physician.
    97% followed for 3 months

    The evidence

    Outcome Time to outcome CER EER RRR
    (95% CI)    		 ARR
    (95% CI)    		 NN T
    (95% CI)
    INR 1.8 to 3.2 24 hours 9
    (20.5%)    		 25
    (55.6%)    		 170%
    (43% to 410%)    		 35.1%
    (16.3% to 53.9%)    		 3
    (2 to 6)
    bleeding episode 3 months 8
    (18.2%)    		 2
    (4.44%)    		 76%
    (-9% to 95%)    		 13.7%
    (0.848% to 26.6%)    		 7
    (4 to 120)

    Comments

    1. Patients were randomised in blocks of four.
    2. One patient in each group had a venous thromboemoblism over the next 3 months.
    3. All episodes of bleeding were considered to be minor.

    Citation

    1. Crowther MA, Julian J, McCarty D, et al: treatment of warfarin-associated coagulopathy with oral vitamin K: a randomised controlled trial. Lancet 2000; 356 : 1551-1553
    Search Terms: from ACP Journal Club
    Contributor: Chris Ball, October 2001
    Reviewer:

    Clinical Question.
    Patient INR 4.0 to 10.0
    Intervention or Exposure oral vitamin K
    Comparison placebo
    Outcome bleeding, INR after 1 day