title: Arterial antithrombotic activity of rivaroxaban, an orally active factor Xa inhibitor, in a rat electrolytic carotid artery injury model of thrombosis.
abstract: Rivaroxaban, an oral, direct factor Xa inhibitor, has been approved in several countries for thromboprophylaxis after elective hip or knee arthroplasty based on favorable benefit-risk profile and improved efficacy compared to enoxaparin in reducing the composite of symptomatic and asymptomatic deep vein thrombosis, nonfatal pulmonary embolism, and all-cause mortality. Given the potential therapeutic utility of factor Xa inhibition in arterial thrombosis, we evaluated the antithrombotic activity of rivaroxaban in a model of arterial thrombosis in anesthetized rats in which thrombotic occlusion was induced by electrolytic injury of the carotid artery. Rivaroxaban, 0.3, 1 or 3 mg/kg, enoxaparin, 10 mg/kg, or vehicle were infused intravenously to anesthetized rats and time to occlusion as well as coagulation parameters monitored following carotid electrolytic injury. Although the lowest dose of rivaroxaban (0.3 mg/kg) did not prolong occlusion time compared to vehicle, rivaroxaban at 1 or 3 mg/kg prevented occlusion in all vessels during the 30-min observation period (median occlusion time >30 min), which was greater than that following a single dose of enoxaparin infused at a dose of 10 mg/kg (median time to occlusion = 21.6 min). Rivaroxaban was also effective following oral dosing at 3 mg/kg. Rivaroxaban's antithrombotic activity was paralleled by dose-dependent increases in prothrombin time (PT) and activated clotting time (ACT) without significant changes in activated partial thromboplastin time. Rivaroxaban also markedly increased Russell's viper venom time (RVVT) and decreased thrombin-antithrombin complex concentrations at all doses. These findings support the potential utility of rivaroxaban in arterial thrombotic disorders such as acute coronary syndrome, stroke and peripheral arterial disease.
authors: Johnson & Johnson Pharmaceutical Research & Development, Welsh and McKean Roads, Spring House, Pennsylvania 19477-0776, USA.
authors: Tom J
authors: TJ
authors: Parry
authors: Zhihong
authors: Z
authors: Huang
authors: Cailin
authors: C
authors: Chen
authors: Margery A
authors: MA
authors: Connelly
authors: Elisabeth
authors: E
authors: Perzborn
authors: Patricia
authors: P
authors: Andrade-Gordon
authors: Bruce P
authors: BP
authors: Damiano
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D020212:Carotid Artery Injuries / Q000097:blood* / Q000139:chemically induced; D054059:Coronary Occlusion / Q000097:blood* / Q000139:chemically induced; D003328:Coronary Thrombosis / Q000097:blood* / Q000139:chemically induced; D004195:Disease Models, Animal; D004573:Electrolytes / Q000009:adverse effects; D017984:Enoxaparin / Q000008:administration & dosage / Q000627:therapeutic use; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D009025:Morpholines / Q000008:administration & dosage* / Q000627:therapeutic use; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D051381:Rats; D017207:Rats, Sprague-Dawley; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D004573:Electrolytes; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban; D015951:Factor Xa