New anticoagulants - towards the development of an "ideal" anticoagulant

Currently available anticoagulants, such as unfractionated heparin, low molecular weight heparins and vitamin K antagonists, have proved effective in the prevention and treatment of thromboembolic disorders. However, these drugs have some drawbacks, such as unpredictability (in the case of unfractionated heparin), non-specificity and parenteral mode of administration, which limit their use in the clinical setting. There is a need for new agents with efficacy similar to that of these classes of anticoagulants and none of their associated drawbacks. Advances are being made in the development of more convenient and more specific drugs, with the aim to improve substantially the prevention and management of thromboembolic disorders. This review will emphasize how the development of an ideal anticoagulant, with potential benefits including high efficacy, safety, low levels of bleeding, fixed dosing, rapid onset of action, ability to bind clot-bound coagulation factors and no requirement for therapeutic monitoring, is a considerable challenge. This review will present the most relevant preclinical data, as well as the clinical studies performed to date, for several drug classes. Direct thrombin inhibitors, such as dabigatran etexilate, will be reviewed, as well as indirect (fondaparinux and idraparinux) and direct (rivaroxaban, apixaban, among others) Factor Xa inhibitors, Factor IXa inhibitors and monoclonal antibodies against Factor IX/IXa.