Results of the Phase III AMPLIFY-EXT trial (Apixaban after the initial Management of PuLmonary embolIsm and deep vein thrombosis with First-line therapY-EXTended Treatment) evaluating the prevention of recurrent venous thromboembolism (VTE) in 2,486 patients who had already completed 6 to 12 months of anticoagulation treatment for VTE, including deep vein thrombosis (DVT) or pulmonary embolism (PE) shows that apixaban (Eliquiq?, Bristol-Myers Squibb Company/Pfizer Inc), an oral direct Factor Xa inhibitor, part of a new therapeutic class, demonstrates superiority withhout increasing the rate of major bleeding. By inhibiting Factor Xa, a key blood clotting protein, apixaban prevents thrombin generation and blood clot formation. The trial-results were published online today in theNew England Journal of Medicine and announced during the 54th Annual Meeting of the American Society of Hematology(ASH) as a Late-Breaker.

Venous thromboembolism, or VTE, encompasses two serious conditions: deep vein thrombosis (DVT), a blood clot in a vein, usually in the leg, that partially or totally blocks the flow of blood; and pulmonary embolism (PE), a blood clot blocking one or more vessels in the lungs. VTE continues to be a major cause of morbidity and mortality, with approximately 900,000 patients in the U.S. and approximately 1 million patients in the EU diagnosed every year.

Primary efficacy outcome
In the AMPLIFY-EXT trial, extended treatment with apixaban 2.5 mg and 5 mg twice daily, demonstrated superiority versus placebo in the reduction of the composite endpoint of symptomatic, recurrent VTE and death from any cause (11.6% in the placebo group, compared with 3.8% and 4.2% in the apixaban 2.5 mg and 5 mg groups, respectively, P<0.001), the primary efficacy outcome of the trial.

Apixaban also was superior to placebo for the predefined secondary efficacy outcome of recurrent VTE and VTE-related death (8.8% in the placebo group, compared with 1.7% in both the apixaban 2.5 mg and 5 mg groups). Both of these endpoints, the primary and secondary efficacy outcomes, were statistically significant (p<0.001).

The rate of the primary safety outcome of major bleeding was comparable across treatment groups (0.2 % for apixaban 2.5 mg; 0.1 % for apixaban 5 mg and 0.5% for placebo). The rate of the composite of major bleeding and clinically relevant non-major bleeding for the 5 mg treatment group (4.3%) was higher versus the placebo group (2.7%), while the rate for the 2.5 mg treatment group (3.2%) was similar to the placebo group.

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Recommended treatment
?Up to 10% of patients will experience a recurrent venous thromboe mbolism event after completing the currently recommended six-to-twelve-month treatment period, suggesting the need for additional prophylaxis,? said Dr. Giancarlo Agnelli, professor of internal medicine, University of Perugia, Italy, director of the Department of Internal and Cardiovascular Medicine and Stroke-Unit, University Hospital, Perugia, Italy; and lead investigator of the study. ?In the AMPLIFY-EXT trial, which added an additional year of treatment, apixaban reduced the composite risk of recurrent venous thromboembolism and total mortality without an increase in major bleeding versus placebo.?

Regulatory status
In May 2011, Bristol-Myers Squibb and Pfizer announced the first regulatory approval for apixaban in the 27 countries of the European Union plus Iceland and Norway for the prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery. On November 20, 2012, Bristol-Myers Squibb and Pfizer announced the European Commission became the first regulatory authority globally to approve apixaban for the prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors. Bristol-Myers Squibb and Pfizer announced on December 6, 2012, that Health Canada approved apixaban for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF).

For more information:
Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI. Apixaban for Extended Treatmentof Venous Thromboembolism. December 8, 2012DOI: 10.1056/NEJMoa1207541

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