Practical issues with vitamin K antagonists: elevated INRs, low time-in-therapeutic range, and warfarin failure

Abstract

Millions of patients worldwide are prescribed vitamin K antagonists for a variety of medical conditions annually. Despite widespread and long-standing experience with these medications, medical care providers are often confronted with challenging clinical situations. Vitamin K antagonists have a narrow therapeutic index secondary to intrinsic patient characteristics and extrinsic factors including a propensity for drug-drug interactions. Clinicians are required to titrate doses according to the measured international normalized ratio for each individual, balancing the risk of bleeding with preventing thrombosis. The risk of major bleeding associated with vitamin K antagonists has been reported to range from 1 to 3% per year. This narrative review will provide an overview of the most commonly used vitamin K antagonists and discuss the importance of assessing quality of anticoagulation with respect to clinical outcomes. Practical approaches to managing excessive anticoagulation, variable anticoagulation, and anticoagulation failure will be provided, drawing on evidence where applicable and expert opinion where evidence is limited.

Appropriateness of Dabigatran and Rivaroxaban Prescribing for Hospital Inpatients

“…[12][13][14] Despite its recent approval (in 2008), dabigatran surpassed warfarin in terms of the number of postmarketing surveillance reports to the FDA in 2011 and 2012. 15,16 Because of these safety concerns with dabigatran use, the Institute for Safe Medication Practices Canada considers it an important priority to make the use of anticoagulants, especially dabigatran, safer.…”

Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin

“…3 Patients with higher TTR tend to have fewer thromboembolic and major bleeding events. 43 Higher % TTR in the current metaanalysis translated into lower risks of major bleeding at .…”

“…1 Because warfarin has a narrow therapeutic range as measured by international normalized ratio (INR), 2 and being outside of the therapeutic range in either direction can have devastating eff ects, appropriate dosing is a major clinical issue; a subtherapeutic INR increases risk of thrombosis, whereas a supratherapeutic INR increases bleeding risk with associated morbidity and mortality. 3 Of note, warfarin toxicity has been reported to account for . 10% of all adverse drug reactions leading to hospital admission.…”

Impact of GGCX polymorphisms on warfarin doserequirements in atrial fibrillation patients

“…Due to interindividual differences in drug responses, warfarin has a narrow therapeutic range and inadequate or excessive warfarin may result in thromboembolism or bleeding (8). Therefore, it is essential to monitor and control the warfarin dose within this therapeutic window in clinical application.…”