n period. Rates of the composite of PE and death were lower for rivaroxaban compared with enoxaparin in the planned treatment period and follow up . Future research needs to assess whether changing the timing of the first dose could improve the safety GDC-0449 Vismodegib profile without significantly affecting efficacy. In theory, the earlier Thrombosis 7 an anticoagulant is given, the better the efficacy, but at a cost of increased bleeding. Conversely, the longer anticoagulation is delayed, the lower the risk of bleeding, but efficacy may decrease too. 3. Summary and Conclusions Among the numerous oral anticoagulants currently in phase II and III development, three of the oral agents apixaban, dabigatran and rivaroxaban hold considerable potential benefits for improving thromboprophylaxis strategies.
In light of recent promising findings, more studies on direct E7080 thrombin inhibitors and Factor Xa inhibitors are likely. In addition, reports from daily clinical practice will indicate whether the new agents will change current practice. A phase III TKA study has shown that apixaban is significantly more effective than the once daily enoxaparin regimen, without an increase in bleeding. The phase III studies comparing dabigatran with enoxaparin were designed to show the noninferiority of dabigatran. It was found that dabigatran has similar efficacy and safety compared with the once daily enoxaparin regimen in THA and TKA. In addition, phase III studies have shown significantly improved efficacy and similar safety for rivaroxaban compared with both once daily and twice daily enoxaparin regimens in THA and TKA.
All of these agents provide the benefit of oral dosing without the need for monitoring or dose adjustment, thereby improving the convenience of prophylaxis. Disclosures The author has received research or institutional support from Boehringer Ingelheim and Astellas US and has been a paid consultant for Astellas US, Boehringer Ingelheim, Johnson & Johnson, and DJO Surgical. Acknowledgments The author would like to acknowledge LiWan who provided medical writing services with funding from Bayer Schering Pharma AG and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. The history of antithrombotics Anticoagulants are recommended for the prevention and treatment of venous thromboembolism, and the prevention of thromboembolic events in patients with chronic conditions such as atrial fi brillation , or in patients with mechanical heart valves.
For the prevention of VTE, the American College of Chest Physician guidelines recommend that extended thromboprophylaxis should be given to patients for up to 35 days following total hip replacement and for at least 10 days after total knee replacement . Currently available anticoagulants comprise the heparins unfractionated heparin and the low molecular weight heparins, eg enoxaparin, tinzaparin, dalteparin the vitamin K antagonists, including warfarin, and the synthetic pentasaccharide fondaparinux. Although effective, these agents have signifi cant limitations. UFH, developed more than 60 years ago, requires parenteral administration, making it inconvenient for use outside the hospital setting. It also requires coagulation monitoring and is associated with heparin induced thrombocytopenia and osteopenia. The LMWHs, developed in the 1980s, overcame some of the drawbacks associated with UFH: they do not require monitoring and have a substantially lower risk of HIT compared with UFH. However, LMWHs are admini