Anticoagulant therapy with direct oral anticoagulants in the context of polypragmasy: a course to safety

Cardiovascular disease is the most common cause of death in the world. For almost 60 years vitamin K antagonists (VKAs) have been the mainstay of anticoagulant therapy, but in recent years direct oral anticoagulants (DAACs) have become the anticoagulant of choice, as they have many well-known advantages: more predictable anticoagulant effect, no need for dose selection (there is a need for dose adjustment only for renal dysfunction), routine laboratory monitoring of pharmacodynamic effect (except in special clinical situations), less frequency of clinically significant drug interactions compared with warfarin, and less dependence on patient genetic characteristics. The main indications for POAC are: prevention of venous thromboembolism in patients who have undergone endoprosthesis of lower limbs, prevention of stroke and systemic embolism in patients with atrial fibrillation, treatment and prevention of recurrent deep vein thrombosis (DVT) and pulmonary embolism. The administration of direct oral anticoagulants (DOACs) has long been considered a major therapeutic advance, mainly because they do not require therapeutic monitoring. Despite this, POACs, like vitamin K antagonists, can still cause major and clinically significant minor bleeding, even when used correctly. Considering that POAC patients are often older and have multiple comorbidities, polypragmasy is widespread. Drug interactions involving POACs are important contributors to the increased risk of bleeding. Awareness of these drug interactions and how to address them is critical to optimizing treatment while reducing the risk of bleeding. This review provides an overview of POAC metabolism, the most common drugs that may interact with POACs, and ways to eliminate these interactions.