Stephan Moll, MD writes…
An important study (called AMPLIFY trial) was published today in the New England Journal of Medicine [ref 1]. In a large study of patients with acute DVT or PE, Eliquis (apixaban) was as effective as warfarin and caused less major bleeding.
Eliquis is one of the big 4 new oral anticoagulants that do not need routine monitoring of their blood thinning effect and are not influenced by dietary vitamin K intake. This makes them more convenient to take. The 4 major drugs are:
- Xarelto (rivaroxaban): At this point this is the only one of the new oral anticoagulants that is FDA-approved in the U.S. for the treatment of DVT and PE.
- Pradaxa (dabigatran): Only FDA-approved for atrial fibrillation. In other countries it is also approved for DVT and PE treatment.
- Eliquis (apixaban): Also only FDA-approved for atrial fibrillation.
- Edoxaban: At this point not approved for any indication in the U.S.; approved in Japan for the prevention of DVT and PE after orthopedic surgeries.
- Today’s published study was a good quality (randomized, double-blind) large trial – 5395 patients with acute DVT (65 %), PE (25 %) or both (ca. 10 %) were enrolled.
- Patients either received (a) apixaban (10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months) without initial heparin or low molecular weight (LMWH) injections, or (b) conventional therapy with warfarin with the appropriate bridging injections of LMWH.
- Patients were followed for 6 months.
- Endpoints: (a) Rate of recurrent DVT or PE and (b) major and clinically relevant bleeding.
Apixaban was as effective as warfarin, and safer.
a) Effectiveness: In the apixaban group, 2.5 % of patients had a new DVT or PE, compared to 2.7 % in the warfarin group. Thus, it was as effective as warfarin.
- Major bleeding occurred in 0.6% of patients on apixaban and in 1.8% of warfarin treated patients. This indicates that apixaban was safer than warfarin.
- The combined outcome of major bleeding and clinically relevant non-major bleeding occurred in 4.3% of the patients in the apixaban group, as compared with 9.7% of those in the warfarin group. Again, this indicates that apixaban was safer than warfarin.
Apixaban without the need for monitoring of its blood thinning effect was as effective (non-inferior) to conventional warfarin therapy for the treatment of acute DVT and PE, and was associated with significantly less major and clinically relevant bleeding.
- These are good news: A blood thinner for the treatment of acute DVT and PE that is as effective as warfarin, yet safer, is good to have. In addition, for many patients the new oral anticoagulants are more convenient than warfarin, due to the lack of monitoring need and vitamin K interactions.
- Apixaban in this study design was given right off the bat, i.e. without injections of low molecular weight heparin. Such injections are needed when starting warfarin. This also makes treatment with apixaban much less cumbersome than warfarin therapy.The same study design was used in the rivaroxaban DVT and PE trials [ref 2,3]. The Dabigatran trials [ref 4], on the other hand, required several days of an injection blood thinner, before dabigatran was started. This puts dabigatran at a clear disadvantage to rivaroxaban and apixaban. The same disadvantageous study design is used in the ongoing edoxaban study
- At this time I would not use apixaban off label for treatment of DVT and PE. Xarelto is the only one of the new oral anticoagulants that has been FDA reviewed and approved for the treatment of acute DVT and PE [ref 2,3]. Hopefully, though, FDA application of apixaban and decision about approval will follow soon.
- Regarding the other new oral blood thinners: Dabigatran DVT and PE trials have been completed [ref 4], but it is unclear to me, whether the company is pursuing FDA application for DVT and PE treatment. Results of the edoxaban DVT and PE trial (called HOKUSAI trial) will likely be available in the autumn of 2013.
- Agnelli G et al. Oral Apixaban for the Treatment of Acute Venous Thromboembolism. N Engl J Med, July 1, 2013.
- The Einstein Investigators: Oral Rivaroxaban for symptomatic venous thromboembolism. New Engl J Med 2010;363:2499-510.
- The Einstein Investigators: Oral Rivaroxaban for the treatment of symptomatic pulmonary embolism. New Engl J Med 2012;366:1287-97.
- Schulman S et al. N Engl J Med. 2009 Dec 10;361(24):2342-52.
Disclosure: I have consulted for Janssen, Boehringer-Ingelheim, and Daiichi.
Last updated: July 1st, 2013