Rivaroxaban, a new oral anticoagulant for the prevention of venous thromboembolism after elective hip or knee replacement surgery

摘要

Study objectives: To review the pharmacology, mechanism of action and clinical data on rivaroxaban, a selective, direct Factor Xa inhibitor which has been approved in the EU and several other countries worldwide for the prevention of venous thromboembolism (VTE) after elective hip or knee replacement.Methods: A literature review of the currently available pharmacological and clinical data.Results: Rivaroxaban targets free and clot-bound Factor Xa and the prothrombinase complex. It has a rapid onset of action (k_(on) 1.7 x 107 M1 s~1), inhibiting Factor Xa in a reversible manner (koff 5 x 10~3 S"1). Rivaroxaban is rapidly absorbed, reaching maximum plasma concentration 2-4 hours after oral administration and has a mean terminal half-life of 7-11 hours at the 10 mg dose. The absolute bioavailability of rivaroxaban is high, reaching 80-100%. Rivaroxaban has several potential advantages over conventional anticoagulants, including fixed dosing, minimal clinically relevant drug interactions and no food interactions. No dose adjustment is necessary for age, weight, gender, or mild or moderate renal impairment, and there is no requirement for routine coagulation monitoring because rivaroxaban was found to have predictable and consistent pharmacokinetics and pharmacodynamics. Rivaroxaban regimens have also demonstrated superior efficacy to enoxaparin regimens for the prevention of VTE after total hip or knee replacement surgery, with no statistically significant difference in the incidence of major bleeding. Conclusion: Rivaroxaban could represent an effective and convenient new therapeutic option for the prevention of VTE after elective hip or knee replacement surgery, both in the inpatient and outpatient settings.