Apixaban to Treat Venous Thromboembolism

Atlanta—Patients who took 2.5 mg or 5 mg of apixaban twice daily for 1 year had an 80% risk reduction in recurrent nonfatal or fatal venous thromboembolism (VTE) compared with those who received placebo, according to a randomized, double-blind, placebo-controlled study. The reduction was similar for venous or arterial events. Major bleeding rates were low and similar in all 3 groups.

Giancarlo Agnelli, MD, the study’s lead author and director of the department of internal and cardiovascular medicine and stroke-unit at Perugia University Hospital in Italy, presented the findings in a late-breaking abstract session at the ASH meeting. Results were simultaneously published online in the New England Journal of Medicine [doi:10.1056/NEJMoa1207541]. Bristol-Myers Squibb and Pfizer Inc., the drug’s marketers, sponsored the study.

On December 28, 2012, 3 weeks following Dr. Agnelli’s presentation, the FDA approved apixaban, an oral factor Xa inhibitor, to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

Dr. Agnelli said 6% to 10% of patients with VTE without a reversible risk factor have a recurrence each year. VTE is a disease state that includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Although warfarin is effective in treating VTE, it leads to increased risk of bleeding, and a reduction in warfarin contributes to less efficacy without reducing the bleeding risk.

In the AMPLIFY-EXTENSION (Apixaban After the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy-Extended Treatment) trial, 2486 patients were enrolled at 328 sites in 28 countries from May 2008 through July 2011. They were randomized to receive 2.5 mg of apixaban, 5 mg of apixaban, or placebo twice daily for 12 months. Each patient had DVT or PE and had completed 6 to 12 months of anticoagulant treatment.

The treatment groups were comparable in terms of age (mean of 57 years), sex (approximately 58% males), initial diagnosis (65% DVT and 35% PE), and other baseline characteristics.

After a year of therapy, 8.8% of patients who received placebo had recurrent VTE or VTE-related death compared with 1.7% of patients in either of the apixaban groups, which Dr. Agnelli said was an 80% risk reduction. In addition, 10.0% of patients in the placebo group had recurrent VTE, VTE-related death, myocardial infarction, stroke, or cardiovascular-related death compared with 2.1% of patients in the 2.5-mg apixaban group and 2.3% of patients in the 5-mg apixaban group, which was also approximately an 80% risk reduction when taking either dose of apixaban.

Further, 11.0% of patients in the placebo group had recurrent VTE or all-cause death compared with 3.8% of patients in the 2.5-mg apixaban group and 4.2% of patients in the 5-mg apixaban group.

Major bleeding occurred in 4 patients in the placebo group (intraocular, stroke, urogenital, and gastrointestinal), 2 patients in the 2.5-mg apixaban group (both intraocular), and 1 patient in the 5-mg apixaban group (gastrointestinal). In the placebo group, 2.3% of patients had clinically relevant non-major bleeding compared with 3.0% of patients in the 2.5-mg apixaban group and 4.2% of patients in the 5-mg apixaban group. Major or clinically relevant non-major bleeding occurred in 2.7% of patients who took placebo, 3.2% of patients who took 2.5 mg of apixaban, and 4.3% of patients who took 5 mg of apixaban.