Pharmacological characteristics of novel oral anticoagulant drugs for thromboprophylaxis in atrial fibrillation

Atrial fibrillation (AF ) is associated with increased risk of thromboembolic complications that are frequently fatal or associated with permanent disability. The most effective prevention of AF -related thromboembolism is achieved with oral anticoagulant therapy. Until recently, the only available option for chronic oral anticoagulant therapy was treatment with vitamin K antagonists which is limited by the numerous food and drug interactions and a narrow therapeutic window that requires frequent monitoring of anticoagulation intensity. Lately, significant progress has been made in AF thromboprophylaxis with the arrival of novel oral anticoagulant medications (NOAC s) that act as reversible direct inhibitors of activated factor II (dabigatran) or activated factor X (rivaroxaban, apixaban, edoxaban) in the blood. All NOAC s have a predictable, dose-dependent pharmacological effect with a rapid onset (~1 to 4 h after oral intake) and offset (~12 to 24 h after the last dose) of action, without requirements for routine monitoring of anticoagulation intensity. Food has no impact on NOAC s absorption, with the exception of rivaroxaban that has improved bioavailability when taken with food. Unlike vitamin K antagonist, clinically relevant drug-drug interactions of NOAC s are rare and mostly related to concomitant therapy with strong cytochrome P450 inducers/ inhibitors or p-glycoprotein inhibitors. All NOAC s are renally excreted (particularly dabigatran), therefore caution is advised in patients with renal impairment. NOAC s are contraindicated in advanced renal or hepatic insufficiency, in patients on dialysis and in subjects with mechanical heart valves. The purpose of this review article is to provide the most important information on pharmacological characteristics of NOAC s, with an overview of the established drug-drug interactions and current options for the monitoring of anticoagulation intensity, if requred in special clinical circumstances.