Oral anticoagulation with factor Xa and thrombin inhibitors: on the threshold of change

Since the discovery of vitamin K antagonists in the early 1940s, there has been little change in anticoagulation until, in the 1990s, widespread use of low-molecular-weight heparin. Within the next few years, the treatment of arterial and venous thromboembolism is again poised to undergo a major change with the introduction of new oral anticoagulants that are likely to fulfill many of the unmet needs of current warfarin therapy. New drug development has focused on inhibiting specific coagulation factors, with those targeting thrombin and factor Xa being most advanced in development.

Several landmark studies are now available on the direct thrombin inhibitor, dabigatran etexilate, and the two factor Xa inhibitors, rivaroxaban and apixaban. Recently, dabigatran etexilate received European approval for venous thromboembolism prevention following orthopedic surgery. Rivaroxaban is currently also approved in Europe and Canada for venous thromboembolism prevention in orthopedic surgery, with US Food and Drug Administration approval expected in 2009.

New oral anticoagulant approval may provide safer and easier venous thromboembolism prevention and treatment than warfarin. As we stand on this threshold, this article reflects on anticoagulation breakthroughs, summarizes recent studies, and discusses potential drawbacks.