Introduction

Abstract

Warfarin and other coumarin derivatives have long been the mainstays of oral anticoagulant therapy. While evidence has proven them effective for treating and decreasing the risk of thromboembolism, these agents also have many burdensome traits for use for both the clinician and patient. As narrow therapeutic index drugs, the therapeutic window between efficacy and toxicity is small with little correlation between dose and therapeutic effect. Genetic factors and other interpatient variability, such as diet and drug-drug interactions, also contribute to the wide dose range and need for frequent monitoring of the international normalized ratio (INR). The alternatives to oral anticoagulants used to only include injectable anticoagulants which were often utilized in place of or in addition to warfarin until a therapeutic INR was obtained. These injectable agents limitations were mainly in cost and route of administration, and thus lack of patient acceptance. Fortunately, we have entered an era where several viable oral anticoagulant alternatives exist. These direct oral anticoagulants have much more predictable dose-response profiles thus eliminating the need for frequent monitoring. In addition, they have few dietary precautions and much less drug-drug interactions. However, these agents are not benign, not interchangeable, and not entirely characterized in regards to drug-drug interactions, reversibility, or use in populations outside of those in the pivotal clinical trials. Dosing, although more predictable in response, does have limitations including various doses and renal doses based on indication. As such, management of all the anticoagulants, whether warfarin, injectable, or the direct acting oral anticoagulants, is complicated and very patient specific. A need for extensive education of health care professionals is required.