Extending Anticoagulation With Apixaban Reduces Recurrent VTE

Extended anticoagulation with fixed doses of the oral Factor Xa inhibitor apixaban significantly reduced the incidence of symptomatic recurrent venous thromboembolism (VTE) or death without increasing the risk of major bleeding in patients with VTE who had already completed up to 12 months of anticoagulation.

In a phase III clinical trial known as AMPLIFY-Extension, apixaban administered for 1 year reduced the risk of the primary composite efficacy endpoint—recurrent VTE and death from any cause—by approximately 80% compared with placebo, said Giancarlo Agnelli, MD, the study’s principal investigator. He presented the findings at the 54th Annual Meeting of the American Society of Hematology.

The risk of recurrent VTE is approximately 6% to 10% per year in patients following discontinuation of warfarin anticoagulation, said Dr Agnelli, Professor, Internal Medicine, University of Perugia, Italy. Whether extending the duration of anticoagulation beyond the currently recommended 6 to 12 months would continue to reduce thrombotic risk in patients with VTE had not been known.

In the AMPLIFY-Extension trial, 2486 patients with prior VTE who had completed 6 to 12 months of anticoagulation were randomized in a double-blind fashion to treatment with apixaban at either 2.5 mg twice daily or 5 mg twice daily or placebo twice daily for 12 months.

Both dosages of apixaban were significantly superior to placebo (P <.001) on the primary efficacy endpoint. Rates of symptomatic recurrent VTE or death from any cause were 3.8% in the group randomized to 2.5 mg of apixiban twice daily, 4.2% in those randomized to 5 mg of apixaban twice daily, and 11.6% in those randomized to placebo, corresponding to a 65% relative risk reduction with apixaban.

The number needed to treat to prevent one episode of recurrent fatal or nonfatal VTE was 14.

Treatment at either dosage of apixaban also reduced the rates of cardiovascular events, including stroke, myocardial infarction, and cardiovascular-related death, said Dr Agnelli.

“The rates of major bleeding were low and comparable to those in the placebo group,” said Dr Agnelli. Specifically, the rates of major bleeding were 0.2% and 0.1% in the 2.5-mg and 5-mg twice daily apixaban groups, respectively, compared with 0.5% in the placebo recipients.

The rates of clinically relevant non-major bleeding were also not significantly different between the active treatment and placebo groups. These rates were 3.0% and 4.2% with 2.5 mg and 5 mg twice daily of apixiban, respectively, and 2.3% with placebo. The number needed to treat to cause 1 episode of major or clinically relevant non-major bleeding episode was 200.

According to Agnes Y. Lee, MD, Medical Director, Thrombosis Program, Associate Professor of Medicine, University of British Columbia, Vancouver Coastal Health, Canada, apixaban has an advantage over the other new oral anticoagulants in that it is least dependent on renal clearance. “It clearly gives us another therapeutic option,” she said. “This is important because many patients with thromboembolic complications do have renal compromise."