New Oral Anticoagulants
Now that the four new oral anticoagulants—dabigatran, rivaroxaban, apixaban, and edoxaban—have completed phase 3 trials for the treatment of acute venous thromboembolism (VTE),1-5 all with positive outcomes compared with unfractionated heparin (UFH)/low–molecular-weight heparin (LMWH)/warfarin, are these drugs to be considered the go-to agents for these conditions? All agents showed noninferiority to standard therapy with regard to efficacy, and three showed superiority in reducing major and clinically relevant nonmajor bleeding (see table below).
While these agents have great advantages over warfarin, such as limited drug interactions, no dietary interactions, no need for monitoring and, for two drugs, no need for a lead-in phase as with UFH/LMWH, there still are questions to be resolved: Are these drugs appropriate for all causes of VTE (eg, cancer-associated VTE, thrombophilia)? Is a fixed dose appropriate for all patients? How best to manage therapy when there are no sensitive and readily available plasma assays to measure drug effect? How to manage major bleeding without a proven reversal agent? And how to manage therapy in the setting of liver or renal failure?
These are just a few questions requiring further study and real-world experience before these new agents automatically become the preferred treatment for all patients. Until then, UFH/LMWH and well-managed warfarin still are effective therapies with decades of experience behind them. However, the new agents have compelling advantages for the patient with what might be considered the average case of deep vein thrombosis or pulmonary embolism, and physicians must consider with each case what’s best for a particular patient.
— Jack E. Ansell, MD, MACP, is past chair of medicine at Lenox Hill Hospital in New York City and a professor of medicine at Hofstra North Shore-LIJ School of Medicine. A clinical investigator with a principal focus on the clinical problems of thrombosis, antithrombotic therapy, and the application of new modes of delivering and monitoring anticoagulants, he has helped to identify and provide an understanding of the problems related to warfarin therapy management and was one of the first investigators to identify and show that patients can manage their own therapy through home monitoring.
Hazard Ratio, Relative Risk, or Odds Ratio of Selected Outcomes for the Novel Oral Anticoagulants in Comparison to a Vitamin K Antagonist
— Table adapted from Mantha S, Ansell J. Indirect comparison of dabigatran, rivaroxaban, apixaban, and edoxaban for the treatment of acute venous thromboembolism. J Thromb Thrombolysis. In press. Used with permission.
2. Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499-2510.
3. Buller HR, Prins MH, Lensin AW, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287-1297.
4. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799-808.
5. Buller HR, Decousus H, Grosso MA, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406-1415.