Pharmacokinetics and drug interaction of new anticoagulants: Direct thrombin inhibitor and factor Xa inhibitors

Vitamin K antagonists (VKA) such as warfarin are highly effective in preventing recurrent ischemic stroke of cardiac origin due to atrial fibrillation. During the last five decades, little progress has been made in the development of oral anticoagulants, and warfarin is the only oral anticoagulant currently recommended for the prevention of stroke in patients with moderate to high risk of stroke. Although effective, VKA have unpredictable pharmacologic effects, requiring regular coagulation monitoring and dose adjustment to maintain effects within the therapeutic range. These limitations increase the complexity of VKA use in the clinical setting, creating a burden for patients, physicians, and pharmacists. Therefore, the current focus of clinical development is on new oral anticoagulants that directly target thrombin or activated factor X(FXa). These new anticoagulants are more convenient than VKA, with predictable anticoagulant response, low potential of drug-drug interactions, and using fixed doses without coagulation monitoring. Recently, some of these drugs have been approved in the EU, Canada, and Japan for the prevention of thromboembolism in patients undergoing hip- and knee-replacement surgery, prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation, or prevention of cardiac events in patients with acute coronary syndromes. This review summarizes the pharmacokinetic properties and drug interactions of new anticoagulants (dabigatran etexilate, edoxaban, rivaroxaban, apixaban, idrabiotaparinux).