A fixed-dose regimen of oral apixaban alone was as effective as conventional therapy for the treatment of acute venous thromboembolism, according to results from the AMPLIFY Trial published in the New England Journal of Medicine. In addition, apixaban had a significant reduction in major bleeding.

The trial, based on data from approximately 5,400 patients with acute venous thromboembolism (objectively confirmed, symptomatic proximal deep-vein thrombosis or pulmonary embolism with or without deep-vein thrombosis) at 358 centers in 28 countries between August 2008 and Augusts 2012, compared apixaban (10 mg twice daily for seven days, followed by 5 mg twice daily for six months) with conventional therapy (subcutaneous enoxaparin, followed by warfarin).

Overall results showed apixaban was noninferior to conventional therapy (P<0.001). The primary efficacy outcome of recurrent symptomatic venous thromboembolism or death related to venous thromboembolism occurred in 2.3 percent of patients in the apixaban group, compared to 2.7 percent in the conventional therapy group.

Additionally, major bleeding occurred in 0.6 percent of patients receiving apixaban, compared to 1.8 percent receiving conventional therapy (relative risk, 0.31; P<0.001 for superiority). The composite outcome of major bleeding and clinically relevant nonmajor bleeding occurred in 4.3 percent of patients in the apixaban group, compared to 9.7 percent in the conventional therapy group. "The reduction in major bleeding was paralleled by a decrease in clinically relevant nonmajor bleeding, which provides further evidence for the safely of this apixaban regimen," the study investigators said. They also noted that the rates of other adverse events, including elevations in liver-function tests, were similar across the two treatment groups.

Moving forward, the investigators noted that the AMPLIFY findings "add to the evidence that the new oral anticoagulants are simple alternatives to conventional therapy for patients with acute venous thromboembolism." However, they suggest that additional information is needed about the efficacy and safety of apixaban in patients with cancer, low body weight, or a creatinine clearance of less than 50 ml per minute.

Mary Cushman, MD, echoes the need for additional information in an editorial comment. "As we translate knowledge from the era of vitamin K antagonists to new agents ... more information is needed on reversal strategies, monitoring, … approaches to treatment failure, comparisons of adherence to treatment among new drugs and warfarin, and formal cost-effective analyses," she writes. "After 60 years of warfarin, it is an exciting time in thrombosis care. Shifting with care to new treatments is essential to safe and effective practice."

Keywords: Vitamin K, Treatment Failure, Risk, Neoplasms, Pulmonary Embolism, Body Weight, Venous Thromboembolism, Pyrazoles, Creatinine, Pyridones