The benefits of VKA are largely dependent upon achieving adequate anticoagulation, ideally an INR of between 2 and 3, for the majority of treatment time. However, achieving and maintaining therapeutic anticoagulation in clinical practice can be quite challenging. Warfarin and other VKA have a variety of limitations in clinical practice. The individual patient's response to warfarin is often unpredictable, with a narrow therapeutic window. The drug has a slow onset and offset of action, with the need for regular INR monitoring and frequent dose adjustments. There are often numerous food and drug interactions with warfarin. Patients may be non-compliant with routine INR monitoring. Physicians may be wary of the risk of bleeding complications, particularly the risk of intracranial haemorrhage, which rises substantially once INR approaches 4 or beyond. Such fear of bleeding may lead physicians to underprescribe warfarin to patients at increased stroke risk. Adverse events with warfarin are common, leading to a high rate of discontinuation. As a result of these limitations, it is estimated that only half of eligible AF patients worldwide receive any VKA at all. In those patients receiving VKA, only 40-60% actually achieve therapeutic anticoagulation. The adequacy of anticoagulation with VKA is often termed "Time in Therapeutic Range (TTR)", which estimates the overall period of time that an individual patient or group of patients spend with an INR between 2 and 3. Numerous practice audits and observational registries suggest that the average TTR globally is roughly 45-55%, whereas it is estimated that a TTR of 65% is required to optimally reduce the risk of AF-related stroke.