Stephan Moll, MD writes…
An important study (AMPLIFY trial) was published today in the New England Journal of Medicine [ref 1]: In a large study of 5395 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 anticoagulant effect and are not influenced by dietary vitamin K intake, making them more convenient to take. The 4 major drugs are:
- Xarelto (rivaroxaban): At this point, 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 approved in the U.S. 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. It is approved in Japan for the prevention of DVT and PE after orthopedic surgeries.
- Today’s published study was a randomized, double-blind, large trial of 5395 patients with acute DVT (65 %), PE (25 %) or both (ca. 10 %).
- 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 bridging, or (b) conventional therapy with warfarin with LMWH bridge.
- Patients were followed for 6 months.
- Endpoints: Rate of recurrent venous thromboembolism and of major and clinically relevant bleeding.
Apixaban was as effective as warfarin, and safer.
- Effectiveness: In the apixaban group, 2.5 % of patients had a new DVT or PE, compared to 2.7 % in the warfarin group (relative risk, 0.84; 95% confidence interval [CI], 0.60 to 1.18). Apixaban was non-inferior to warfarin therapy with (P<0.001).
- Major bleeding occurred in 0.6% of patients on apixaban and in 1.8% of warfarin treated patients (relative risk, 0.31; 95% CI, 0.17 to 0.55; P<0.001 for superiority).
- The composite 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 conventional-therapy group (relative risk, 0.44; 95% CI, 0.36 to 0.55; P<0.001). Rates of other adverse events were similar in the two groups.
A fixed-dose regimen of apixaban alone was non-inferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less major and clinically relevant bleeding.
- These are good news: An anticoagulant for the treatment of acute VTE that is as effective as warfarin, yet safer, is good. In addition, for many patients the new oral anticoagulants are more convenient than warfarin, given their lack of monitoring need and vitamin K interactions
- Good is also that the study design was such that apixaban was given immediately upon the diagnosis of VTE, without the initial need for bridging therapy with a parenteral anticoagulant. The same study design was used in the rivaroxaban VTE trials [ref 2,3]. The Dabigatran trials [ref 4], on the other hand, required several days of a parenteral anticoagulant, before dabigatran was started; the same disadvantageous study design applies to the ongoing edoxaban VTE study.
- At this time I would not use apixaban off label for VTE treatment. I’d wait until the FDA has reviewed and approved the drug for the treatment of acute DVT and PE [ref 2,3]. Hopefully, though, apixaban FDA application and a decision about approval will follow soon. At present, Xarelto (rivaroxban) is the only drug FDA-approved for the treatment of VTE.
- Dabigatran VTE trials have been completed [ref 4], but it is unclear to me, whether the company is pursuiting FDA application for VTE treatment. Results of the edoxaban VTE 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 3rd, 2013