Supplementation to Improve Anticoagulation Control with Low Dose Vitamin K as an Adjuvant to Warfarin Therapy: A Double-blind, Placebo-controlled Randomized Controlled Trial

Abstract

Vitamin K Antagonists [VKA] are the most frequently used oral anticoagulants in clinical practice; however, many patients fail to achieve adequate anticoagulation control. We conducted a randomized, placebo controlled, double blind study of Vitamin K1 (200mcg per day, Swanson Vitamins) in a population with predominantly venous thromboembolism aimed at evaluating its effectiveness in improving anticoagulation control in unstable patients. This study also aimed to evaluate the impact that clinical variables, patient anticoagulation knowledge, and genetic polymorphisms in genes known to impact warfarin and Vitamin K metabolism [VKORC1, CYP4F2, CYP2C9] had on anticoagulation control and intervention effectiveness. A total of N=54 patients were enrolled in the study over 15 months [January 2009 to June 2010]. Change score analysis and multivariate linear regression modelling of anticoagulation control measures were performed. No statistically significant reduction was observed in the Vitamin K1 arm for percent time in therapeutic range; however, reduction was observed in standard deviation of INRs [Change Score Vitamin K = -0.259, p=0.0261; Regression Model 95% C.I Beta Vitamin K = 0.38 to -0.08] during the intervention period. Adjusting for treatment group allocation, independent predictors of increased INR standard deviation included: >5 alcoholic drinks per week [95% C.I Beta = 0.04 to 0.41], self-reported dosing errors [95% C.I Beta = 0.13 to 0.47], and missed INR appointments [95% C.I Beta = 0.002 to 0.05]