Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary 
embolism, is a major cause of morbidity and mortality in patients undergoing 
major orthopedic surgery, and routine thromboprophylaxis has been the standard 
of care over the last 20 years. Currently available options for the prevention 
of VTE in major orthopedic surgery include low-molecular-weight heparins, 
vitamin K antagonists and, more recently, the synthetic pentasaccharide 
fondaparinux. Although effective, these drugs have several limitations, and new 
oral antithrombotics offering predictable, effective and safe anticoagulation 
are strongly needed. This overview focuses on the most advanced oral direct 
inhibitors of factor Xa, rivaroxaban, apixaban, LY517717, YM150 and betrixaban. 
Specifically, the results of phase II and III studies and the designs of ongoing 
clinical trials in patients undergoing elective hip and knee replacement are 
reviewed.