The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism

Abstract

Thromboembolic disorders are among the major causes of morbidity and mortality, and anticoagulation remains the cornerstone of prevention and treatment of these disorders. Although effective, the well-established agents have significant drawbacks. Heparin, low molecular weight heparin, and fondaparinux must be given parenterally, which is inconvenient for long-term or home use. The orally administered vitamin K antagonists (such as warfarin) have a slow onset of action, thus requiring bridging therapy with a parenteral agent when immediate anticoagulation is needed (e.g. inpatients with acute deep vein thrombosis). Because vitamin K antagonists produce a variable anticoagulant response as a result of multiple drug-drug and food-drug interactions and genetic polymorphisms, frequent coagulation monitoring and dose adjustment are required to ensure a therapeutic level of anticoagulation, which is inconvenient for both patients and physicians. In the search for new agents to overcome the drawbacks associated with traditional agents, direct Factor Xa inhibitors (e.g. rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitors (e.g. dabigatran etexilate) have been developed and are undergoing late-stage clinical evaluation for the prevention and treatment of thromboembolic disorders. These new oral agents have already shown promise in large-scale clinical studies and data suggest that we have entered a new era with novel drugs that are closer than ever to the 'ideal anticoagulant'. Because these new oral agents have a rapid onset of action and can be given at fixed doses without the need for routine coagulation monitoring, they may simplify treatment paradigms and are expected to improve overall clinical outcome

Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations

“…44 It is eliminated by oxidative metabolism, renal, and intestinal routes. In the ARIS-TOTLE trial, patients with a serum creatinine level of 1.5 mg/dL and atrial fibrillation (AF) received a reduced dose of 2×2.5 mg/d (standard dose 2×5 mg/d).…”

Oral fondaparinux: use of lipid nanocapsules as nanocarriers and in vivo pharmacokinetic study

“…4 For the new oral direct factor Xa inhibitors and direct thrombin inhibitors, 1,5 various challenges still remain such as decreasing the incidence of bleeding side effects. 4,6,7 There is thus a rationale to develop an oral formulation of Fp.…”

Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism

“…[5][6][7][8][9] Recently developed oral anticoagulants that are directed against factor Xa or thrombin overcome some limitations of standard therapy, including the need for injection and for regular dose adjustments on the basis of laboratory monitoring. 5,10,11 Current data suggest that rivaroxaban, an oral direct inhibitor of factor Xa, is effective and safe for the prevention of venous thromboembolism after major orthopedic surgery, for the prevention of stroke in patients with atrial fibrillation, and in the treatment of acute coronary syndromes. [12][13][14] The EINSTEIN program evaluated the concept of using rivaroxaban alone for anticoagulant therapy for acute deep-vein thrombosis and pulmonary embolism, replacing both heparin and vitamin K antagonists.…”