Apixaban: Effective in Acute VTE; Lower Risk of Major Bleeding

July 18, 2013

Oral apixaban for acute VTE was superior to enoxaparin followed by warfarin.

Traditionally, treatment options for acute venous thromboembolism (VTE) have been limited to parenteral agents (ie, heparin) followed by vitamin K antagonists (VKA) titrated to the therapeutic range. This medication regimen may include complicated bridging and transition strategies and poses risks for medication errors. The novel oral anticoagulant agents, however, offer alternative simple first-line strategies for anticoagulation in treatment of acute VTE. Rivaroxaban has already been studied as an alternative to VKAs in the EINSTEIN trialand dabigatran was studied in the RE-COVER trialin the treatment of acute VTE.

Apixaban (an oral factor Xa inhibitor) was recently studied by the AMPLIFY investigators in a similar large, randomized, non-inferiority, double-blind study.3 The new drug was compared with conventional therapy (subcutaneous enoxaparin followed by warfarin with INR goal between 2.0 and 3.0) in 5395 patients with deep venous thrombosis (DVT) or pulmonary embolism (with or without DVT). Initial apixaban dosing was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. The primary safety outcomes were major bleeding and major bleeding plus clinically relevant non-major bleeding.3

The results, just published in The New England Journal of Medicine,3 reported a rate of symptomatic recurrent VTE or death related to VTE (primary efficacy outcome) of 2.3% in the apixaban arm vs 2.7% in the conventional therapy group (relative risk = 0.84; P < .001 for non-inferiority). The major safety outcome (major bleeding) was lower in the apixban arm vs conventional therapy (0.6% vs 1.8%; relative risk = 0.31; P < .001 for superiority). The results were similar for the composite of major and clinically relevant non-major bleeding (4.3% vs 9.7%; relative risk = 0.44; P < .001).

On the basis of this study and previous data showing efficacy of apixaban in the extended treatment of VTE,4 apixaban offers a new option for both acute and extended treatment of VTE, with a lower risk of major bleeding. Additional studies are needed to determine whether apixaban can be safely used in patients with renal dysfunction or those with previous bleeding episodes.

References
1. Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499-2510. (The EINSTEIN trial) (Full text)
2. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361:2342-2352. (The RE-COVER trial) (Full text)
3. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;10.1056/NEJMoa1302507. (Full text)
4. Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboemoblism. N Engl J Med. 2013;368:699-708. (Abstract)