Vitamin K antagonist use: evidence of the difficulty of achieving and maintaining target INR range and subsequent consequences

Vitamin K antagonists (VKAs) are effective oral anticoagulants that are titrated to a narrow therapeutic international normalized ratio (INR) range. We reviewed published literature assessing the impact of INR stability - getting into and staying in target INR range - on outcomes including thrombotic events, major bleeding, and treatment costs, as well as key factors that impact INR stability. A time in therapeutic range (TTR) of ≥65 % is commonly accepted as the definition of INR stability. In the real-world setting, this is seldom achieved with standard-of-care management, thus increasing the patients' risks of thrombotic or major bleeding events. There are many factors associated with poor INR control. Being treated in community settings, newly initiated on a VKA, younger in age, or nonadherent to therapy, as well as having polymorphisms of CYP2C9 or VKORC1, or multiple physical or mental co-morbid disease states have been associated with lower TTR. Clinical prediction tools are available, though they can only explain <10 % of the variance behind poor INR control. Clinicians caring for patients who require anticoagulation are encouraged to intensify diligence in INR management when using VKAs and to consider appropriate use of newer anticoagulants as a therapeutic option.