Summary
Heparins, either unfractionated or low-molecular-weight (UFH and LMWHs), and vitamin
K antagonists (VKAs) are currently the anticoagulants of choice for the prevention
of post-operative venous thromboembolism (VTE) and for the treatment of acute venous
and arterial thromboembolism. While VKAs are widely used in the US, LMWHs are the
standard of care in the EU. Although efficacious, these agents are associated with
a number of drawbacks, such as the risk of heparin-induced thrombocytopenia, the need
for frequent coagulation monitoring in the case of UFH and VKAs, and the parenteral
mode of administration in the case of heparins, which can lead to problems associated
with patient compliance. There is a need for new anticoagulants that overcome these
limitations. Direct, small-molecule inhibitors of coagulation proteins targeting a
single enzyme in the coagulation cascade – particularly thrombin or Factor Xa – have
been developed in recent years. Two agents, the direct thrombin inhibitor dabigatran
and the direct Factor Xa inhibitor rivaroxaban, have recently been approved in the
EU and several other countries for the prevention of VTE after total hip or knee replacement
surgery. Here we will review data that suggest that the antithrombin-independent mechanism
of action of these agents, particularly that of direct Factor Xa inhibitors, leads
to increased efficacy with similar safety profiles compared with the antithrombin-dependent
heparins. Although the end of the heparins era is not to be expected, the new anticoagulants
presented in this review potentially represent the future of anticoagulation.
Keywords
Factor Xa - direct thrombin inhibitors - antithrombin-dependent inhibitors - rivaroxaban
- heparin
