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. Design: 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. Setting: 14 anticoagulant therapy clinics in Canada, the United States, and Italy. Patients: Nonbleeding patients with INR values of 4.5 to 10.0. Intervention: Oral vitamin K, 1.25 mg (355 patients randomly assigned; 347 analyzed), or matching placebo (369 patients randomly assigned; 365 analyzed). Measurements: 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% Cl, -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 [Cl, -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 [Cl, -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). Limitation: Patients who were actively bleeding were not included, and warfarin dosing after enrollment was not mandated or followed. Conclusion: Low-dose oral vitamin K did not reduce bleeding in warfarin recipients with INRs of 4.5 to 10.0. Funding: Canadian Institutes of Health Research and Italian Ministry of Universities and Research.