Factor Xa or thrombin: is thrombin a better target?

The limitations of the vitamin K antagonists have prompted the development of new oral anticoagulants that target specific clotting enzymes. Most of the novel agents currently under development target either thrombin or factor Xa. As the final effector of blood coagulation and the most potent platelet agonist, thrombin is a logical target for new oral anticoagulants. Clinical trials with parenteral direct thrombin inhibitors revealed that the therapeutic window is wider with reversible inhibitors than with irreversible inhibitors. The results of clinical trials with ximelagatran, an orally active prodrug of melagatran, a reversible direct thrombin inhibitor, validate thrombin as a target. Although ximelagatran was withdrawn from the market because of hepatotoxicity, newer oral thrombin inhibitors, such as dabigatran etexilate, are filling the void. Several oral factor Xa inhibitors also are being tested. Is thrombin a better target for new oral anticoagulants than factor Xa? Only time will tell!