New antithrombotic drugs on the horizon

Venous and arterial thromboembolism are a major cause for morbidity and mortality. The list of established drugs for the prevention of thrombus formation and embolisation includes heparins, hirudin and derivatives, aspirin, ADP and glycoprotein IIb/IIIa receptor antagonists, as well as vitamin K antagonists. Several limitations exist for these drugs that have stimulated the search for new and better anticoagulants. A series of selective clotting factor Xa inhibitors and direct factor IIa (thrombin) inhibitors are on the horizon, two of which are getting close to broad clinical application. Additional therapeutics that are still under preclinical and clinical investigation include inhibitors of the tissue factor pathway/factor VII complex, clotting factor VIII and XIII inhibitors and modulators of the protein C pathway or of endogenous fibrinolysis, as well as novel antiplatelet drugs. This review is focused on the current status of development of novel antithrombotics and their clinical potential. Even though only a few of a broad array of antithrombotic agents have reached clinical testing, some hold the potential for significant improvement in efficacy and safety of anticoagulant therapy.