Novel factor Xa inhibitors for prevention and treatment of thromboembolic diseases.
Novel anticoagulants to replace unfractionated heparins, low molecular weight heparins and vitamin K antagonists, are needed urgently. Coagulation factor Xa is an attractive target for drug development because of its position at the convergence of the intrinsic and extrinsic clotting pathways. There are two differing strategies of inhibiting factor Xa that are being pursued: indirect inhibition by compounds such as fondaparinux and idraparinux, requiring antithrombin as a cofactor; and direct inhibition by compounds such as rivaroxaban (BAY 597939), DX-9065a, otamixaban, LY517717 and YM150. Of these compounds, fondaparinux is approved for the prevention and treatment of venous thromboembolism, and idraparinux is in Phase III for venous thromboembolism treatment and stroke prevention in patients with atrial fibrillation. Rivaroxaban has undergone extensive Phase II studies for venous thromboembolism prevention after orthopaedic surgery, and Phase III studies have begun. In this review, we will discuss the pharmacological effects of factor Xa inhibitors and the latest clinical developments.
Kubitza
Dagmar
D
Bayer HealthCare AG, Clinical Pharmacology, Aprather Weg 18a, Wuppertal, Germany. dagmar.kubitza@bayerhealthcare.com
Haas
Sylvia
S
D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D000077425:Fondaparinux; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use; D009281:Naphthalenes / Q000008:administration & dosage / Q000627:therapeutic use; D009844:Oligosaccharides / Q000008:administration & dosage / Q000627:therapeutic use; D011134:Polysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D011422:Propionates / Q000008:administration & dosage / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use; D013923:Thromboembolism / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D009281:Naphthalenes; D009844:Oligosaccharides; D011134:Polysaccharides; D011422:Propionates; D013876:Thiophenes; C479958:idraparinux; D000069552:Rivaroxaban; D015951:Factor Xa; D000077425:Fondaparinux