Review of Direct Oral Anticoagulants and Guide for Effective Drug Utilization

Tigran Khachatryan; Christopher Hauschild; Jason Hoff; Tahmeed Contractor; Arthur Khachatryan; Huyentran Tran; Bert Matsuo; Alan Jacobson; Anthony Hilliard


Am J Cardiovasc Drugs. 2019;19(6):525-539. 

In This Article

Abstract and Introduction


Direct oral anticoagulants (DOACs) have been developed as a viable and in some cases superior alternative to warfarin. These agents have overcome some of the limitations of warfarin, which has a narrow therapeutic window and many food and drug interactions. DOACs have been demonstrated to have a more predictable and reliable pharmacology and, unlike warfarin, do not require frequent monitoring of anticoagulant effect. For these reasons, the use of DOACs is increasing. Despite the many positive attributes of these agents, limitations and contraindications do exist. An understanding of the pharmacology, indications, and contraindications is therefore crucial for effective patient management. We review the available agents to aid in effective drug utilization.


For decades, warfarin has been used as an anticoagulant for a variety of indications. Initially developed as a rodenticide, it found its way into medical use in the twentieth century. Warfarin acts by inhibiting vitamin K-dependent coagulation factor synthesis in the liver (Figure 1). However, it has a narrow therapeutic window, interacts with various foods and medications, and requires frequent monitoring of the international normalized ratio (INR). The development of direct oral anticoagulants (DOACs) has overcome these shortcomings, and DOACs have generally proven at least as efficacious and well-tolerated as warfarin for most indications, with the notable exception of mechanical valves and mitral stenosis.[1–6] DOACs are broadly classified as direct thrombin or direct Factor Xa inhibitors. The European Society of Cardiology (ESC) and the American College of Cardiology (ACC) recommend that, when oral anticoagulation is initiated in a patient with nonvalvular atrial fibrillation (NVAF), a DOAC is preferred to a vitamin K antagonist.[7,8] In addition, the CHEST guideline for antithrombotic therapy for venous thromboembolism (VTE) recommends DOACs over vitamin K antagonist therapy in patients without an associated cancer diagnosis.[9] The use of DOACs has rapidly increased in the USA, with an equal number of patients receiving warfarin or DOACs for like indications in the year 2014.[10] It is imperative that prescribing physicians are familiar with the pharmacology of these agents and know the differences amongst them so the appropriate agent at the optimal dose can be selected for each patient (Table 1 and Table 2). In this article, we provide a general review of DOACs and a guide for the optimal use of these agents (Table 3 and Table 4).

Figure 1.

Coagulation cascade demonstrating the sites of action for the various anticoagulants