Apixaban

Introduction: Thromboembolic events represent the final common mechanism in the pathogenesis of the most lethal vascular diseases in the developed countries (including acute coronary syndromes, ischemic stroke, deep vein thrombosis, and pulmonary embolism). Anticoagulant drugs, such as vitamin K antagonists (VKAs), heparin, low-molecular-weight heparin (LMWH), and, more recently, fondaparinux, form the cornerstone of prevention and treatment of thromboembolic diseases, and they are among the most widely used drugs in the Western world. However, these agents have important limitations. VKAs have a narrow therapeutic range and unpredictable pharmacokinetics (PK) and pharmacodynamics (PD), which are heavily influenced by genetic factors, drug-drug interactions, and dietary intake of vitamin K. Frequent laboratory monitoring and careful dose adjustment of VKAs are needed to ensure effective anti-thrombotic protection at a reasonably low risk of bleeding. Heparin, LMWH, and fondaparinux require subcutaneous injection, which makes them unsuitable for long-term treatments. Therefore, there is a real need for new, orally active anticoagulants with predictable PK/PD profiles that can be used without laboratory monitoring.
Materials and methods: In this €˜â€˜state of the art'' review, the authors examine literature retrieved from a PubMed Medline search with the keyword apixaban and no limits regarding date or language of publication, type of article, or field.
Results: Apixaban is an oral anticoagulant developed for the prevention and treatment of venous thromboembolism, for stroke prevention in atrial fibrillation, and for secondary prevention in ischemic heart disease. It is a potent, reversible, highly selective, direct inhibitor of free and prothrombinase-bound factor Xa. It is characterized by > 50% oral bioavailability, peak plasma concentrations 1-3 h after administration, and a 12-h terminal half-life. It also has low potential for drug-drug interactions and is eliminated through mixed renal and metabolic pathways (both CYP-mediated and CYP-independent). Apixaban has exhibited promising efficacy and safety profiles in different clinical conditions.
Discussion: Apixaban is a promising new oral anticoagulant. However, additional studies on effectiveness and safety are needed to determine whether it can compete with the coumarins in the prevention and treatment of thromboembolic diseases.