New oral anticoagulants: Considerations of clinical pharmacology

Oral anticoagulant therapy is widely used to prevent and treat thromboembolic events. Traditionally, warfarin has been the drug of choice providing a significant reduction in stroke risk in patients with atrial fibrillation. However, warfarin has several drawbacks, such as a delayed onset of anticoagulant action, a narrow therapeutic index, an unpredictable and variable response. The new oral anticoagulants (NOACs), dabigatran (a reversible direct thrombin inhibitor) and the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban offer fixed dosing, more predictable pharmacokinetics and fewer interactions with drugs and food. Moreover, these drugs seem to provide an improved benefit-risk ratio with respect to thromboembolic events and bleeding complications in a broad patient population. However, significant differences between the four NOACs in terms of pharmacokinetic and safety profile are observed and must be considered to personalize the therapy based on the pathophysiological conditions of the patient. In the present review the pharmacological characteristics of NOACs in relationship to their safety and efficacy profiles will be discussed.