Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial.
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.
Crowther
Mark A
MA
McMaster University, Hamilton, Ontario, Canada.
Ageno
Walter
W
Garcia
David
D
Wang
Luqi
L
Witt
Dan M
DM
Clark
Nathan P
NP
Blostein
Mark D
MD
Kahn
Susan R
SR
Vesely
Sara K
SK
Schulman
Sam
S
Kovacs
Michael J
MJ
Rodger
Marc A
MA
Wells
Phillip
P
Anderson
David
D
Ginsberg
Jeffery
J
Selby
Rita
R
Siragusa
Sergio
S
Silingardi
Mauro
M
Dowd
Mary Beth
MB
Kearon
Clive
C
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*
D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D010919:Placebos; D014812:Vitamin K; D014859:Warfarin