Adverse events associated with the use of direct-acting oral anticoagulants in clinical practice: beyond bleeding complications.

Abstract

Non-vitamin K oral anticoagulants, also known as direct oral anticoagulants (DOACs), have entered themarket in 2008 with the expected breakthrough potential of circumventing limitations related to treatmentwith vitamin K antagonists (eg, warfarin) by virtue of their pharmacological properties. Although dataderived from premarketing randomized clinical trials have largely demonstrated the clinical benefit ofDOACs, especially in terms of reduced risk of intracranial bleeding, it is important to monitor the safetyin the postmarketing phase, which better reflects real-world patients with comorbidities and polypharmacotherapy,in order to assess the actual risk-benefit profile. In this critical review, we aimed to evaluatethe evidence on the latest debated safety issues. In the first section, we will discuss: 1) the need forpharmacovigilance (ie, the science and activities relating to the detection, assessment, understanding,and prevention of adverse effects or any other drug-related problems in the real-world setting), and 2) theimportance of properly interpreting postmarketing data to avoid unnecessary alarm. In the second section,emerging and debated safety issues potentially associated with the use of DOACs in the postmarketingsetting will be assessed: 1) the potential coronary risk (which emerged during the preapproval period);2) the occurrence of liver injury (a risk undetected in clinical trials and highlighted by case reports orseries); and 3) the potential for renal damage (a still unclear safety issue). It is anticipated that hepaticand renal issues still require dedicated postauthorization safety studies to ultimately assess causality.