HealthDay News — Taking apixaban, an oral factor Xa inhibitor, for an additional year after standard treatment reduced recurrent venous thromboembolism without increasing the risk for major bleeding, study data show.
Extending apixaban treatment for 12 months was associated with death or recurrent VTE in about 4% of patients receiving either of two doses, compared with 12% in patients assigned to placebo (P<0.001), Giancarlo Agnelli, MD, from the University of Perugia in Italy, and colleagues reported at the American Society of Hematology (ASH) annual meeting. Study findings were published simultaneously online in the New England Journal of Medicine.
Results from the Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy–Extended Treatment (AMPLIFY-EXT) trial also showed that major bleeding rates were lower with apixaban than placebo, although clinically relevant but nonmajor bleeding events were somewhat more common in patients taking the active drug.
Apixaban remains investigational in the United States, but the drug has received approval in Canada and Europe to prevent stroke and systemic embolism in patients with atrial fibrillation and also for VTE prevention following joint surgery. An FDA decision on U.S. approval is expected in March 2013.
AMPLIFY-EXT involved 2,842 patients with VTE who had completed six to 12 months of anticoagulation therapy without experiencing a second episode, and for whom there was uncertainty regarding continuation or cessation of anticoagulants.
Patients were randomly assigned in a 1:1:1 ratio to receive placebo, a prophylactic dose of apixaban at 2.5 mg twice daily, or apixaban at 5 mg twice daily — the dose for treating a VTE episode — for 1 year.
After one year, 11.6% of patients receiving placebo experienced the composite primary endpoint of symptomatic recurrent VTE or death from VTE, compared with 3.8% of patients in the 2.5-mg and 4.2% of patients in the 5-mg apixaban groups (P<0.001 for both comparisons).
Relative to the placebo group, relative risks for the primary endpoint for the low and high apixaban doses were 0.33 (95% CI: 0.22-0.48) and 0.36 (95% CI: 0.25-0.53), respectively.
The rate of major bleeding was 0.5% in the placebo group, compared with 0.2% and 0.1% in the 2.5- and 5-mg apixaban groups, respectively.
The rates of clinically relevant non-major bleeding were 2.3% in the placebo group, compared with 3.0% and 4.2% in the 2.5-mg and 5-mg apixaban groups, respectively.
To put risk-benefit in perspective, the researchers estimated that treating 14 patients with extended apixaban would prevent one episode of fatal or nonfatal VTE. In contrast, 200 patients would have to be treated to cause one episode of major or clinically relevant nonmajor bleeding.
“Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding,” the researchers wrote.