Oral Vitamin K Versus Placebo to Correct Excessive Anticoagulation in Patients Receiving Warfarin

Abstract

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. To see whether low-dose oral vitamin K reduces bleeding events over 90 days in patients with warfarin-associated coagulopathy. 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. 14 anticoagulant therapy clinics in Canada, the United States, and Italy. Nonbleeding patients with INR values of 4.5 to 10.0. Oral vitamin K, 1.25 mg (355 patients randomly assigned; 347 analyzed), or matching placebo (369 patients randomly assigned; 365 analyzed). Bleeding events (primary outcome), thromboembolism, and death (secondary outcomes). 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). Patients who were actively bleeding were not included, and warfarin dosing after enrollment was not mandated or followed. Low-dose oral vitamin K did not reduce bleeding in warfarin recipients with INRs of 4.5 to 10.0. Canadian Institutes of Health Research and Italian Ministry of Universities and Research.