Breakthroughs in Anticoagulation: Advent of the Oral Direct Factor Xa Inhibitors

Abstract

The oral direct factor Xa inhibitors include rivaroxaban and apixaban that recently have been evaluated comprehensively in multiple randomized clinical trials. Based on the efficacy and safety data from these trials, these novel anticoagulants are disseminating throughout clinical practice for thromboprophylaxis in major lower-extremity joint replacement, acute medical illness, atrial fibrillation, and acute coronary syndromes. The advantages of the xabans over vitamin K antagonists include no requirement for routine anticoagulation monitoring as well as a fast and reliable onset of action. The first perioperative limitation of the xabans is the lack of a routine coagulation test for monitoring their anticoagulant effect in scenarios, such as the timing of surgical procedures, the reversal of xaban-related bleeding, and the conduct of regional anesthesia. A second perioperative limitation is the lack of fully validated clinical reversal agents although prothrombin complex concentrate, recombinant factor VIIa, and factor X concentrate are options for xaban reversal in life-threatening bleeding scenarios. Given their clinical efficacy and advantages, further xabans are in clinical development, with edoxaban already in phase III clinical trials. Although the xabans have ushered in a new paradigm for clinical anticoagulation, further clinical trials are indicated to refine their clinical indications even further, such as anticoagulation for patients with mechanical heart valves.