Edoxaban for prevention of venous thromboembolism after major orthopedic surgery

Abstract

Hiroyuki Kawaji,1 Masaji Ishii,1 Yasunobu Tamaki,1 Kan Sasaki,2 Michiaki Takagi,21Department of Orthopaedic Surgery, Saiseikai Yamagata Saisei Hospital, 2Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, Yamagata, JapanAbstract: Fatal pulmonary thromboembolism is the most serious complication following surgery. Patients undergoing major orthopedic surgeries, including total hip replacement, total knee replacement, and hip fracture surgery, represent a group at particularly high risk of venous thromboembolism. Therefore, prophylaxis for thromboembolic events has been of great concern to surgeons. Edoxaban is a novel, orally available, and highly specific and direct factor Xa inhibitor. This new agent was approved for the prevention of venous thromboembolism in patients undergoing major orthopedic surgery, including total hip replacement, total knee replacement, and hip fracture surgery, by the Japanese Ministry of Health, Labor, and Welfare in 2011. Preclinical and Phase I clinical trials demonstrated several promising properties. Its rapid absorption and short life-time in blood are known. Edoxaban inhibits factor Xa activity directly and selectively. It also has a strong antithrombotic effect without any influence of food intake. Coagulation monitoring is not required. Edoxaban has predictable linear pharmacokinetic and pharmacodynamic profiles. Phase II and III clinical trials have been completed to examine its efficacy and safety in patients undergoing major orthopedic surgery. In these clinical trials, oral administration of edoxaban showed efficacy superior to that of oral placebo or subcutaneously administered dalteparin or enoxaparin. Edoxaban can be regarded as a first choice to prevent venous thromboembolism after major orthopedic surgery.Keywords: edoxaban, thromboprophylaxis, venous thromboembolism, total hip replacement, total knee replacement, hip fracture surgery