Emerging anticoagulants for venous thromboembolism prevention

Abstract

To discuss the advantages and disadvantages of currently available anticoagulants, describe the characteristics of the ideal anticoagulant, and compare and contrast the mechanisms of action, pharmacokinetics, administration, efficacy, safety, and potential for drug interactions of currently available and emerging anticoagulants for prevention of venous thromboembolism (VTE). Despite the proven efficacy of currently available agents for VTE prevention, several shortcomings exist that may prevent their use under various circumstances. These include administration by injection, narrow therapeutic index, unpredictable pharmacokinetics and pharmacodynamics, need for laboratory monitoring, risk for bleeding, and drug interactions. The ideal anticoagulant would overcome many of these issues; in particular, it would be available as an oral formulation. Dabigatran, an oral direct thrombin (factor IIa) inhibitor, and apixaban and rivaroxaban, oral direct factor Xa inhibitors, represent new agents for anticoagulation that may address many of these issues. While not available as an oral agent, desirudin is an additional option and offers increased flexibility when a non-heparin-based injectable anticoagulant is desired. Current literature indicates that these agents generally do not require laboratory monitoring and are safe and effective for VTE prevention in clinical studies of patients undergoing major orthopedic surgery. The development of new anticoagulants that may overcome limitations of existing agents represents an opportunity to further improve outcomes in patients at risk for VTE in orthopedic surgery.