July 1st, 2013
New Anticoagulant Found Safe and Effective in Acute Venous Thromboembolism
In a large clinical trial the new oral anticoagulant apixaban (Eliquis, Pfizer and Bristol-Myers Squibb) was at least as effective as standard therapy and caused fewer bleeding complications in patients with acute venous thromboembolism (VTE). The results of the AMPLIFY (Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy) trial are being presented today at the annual meeting of the International Society on Thrombosis and Haemostasis in Amsterdam and are being published in the New England Journal of Medicine. (The embargo on the trial was lifted early by the Journal after being broken by Reuters.)
The AMPLIFY investigators randomized 5,395 patients with acute VTE to either conventional therapy with enoxaparin and warfarin or apixaban (10 mg twice daily for a week, followed by 5 mg twice daily for 6 months). The rate of recurrent symptomatic VTE or death related to VTE, the primary efficacy outcome, was 2.3% in the apixaban group versus 2.7% in the control group (relative risk 0.84, CI 0.60-1.18). This result met the prespecified criteria for noninferiority. In addition, apixaban was associated with significant reductions in the rate of major bleeding (0.6% versus 1.8%, RR 0.31, CI 0.17-0.55, p<0.001 for superiority) and the rate of major bleeding plus clinically significant nonmajor bleeding (4.3% versus 9.7%, RR 0.44, CI 0.36-0.55, p<0.001).
The results were consistent across a broad range of subgroups and were similar in patients who had pulmonary embolism and in patients who had deep vein thrombosis. The results were similar even when apixaban was compared only with those centers where warfarin was used most skillfully.
The study results “add to the evidence that the new oral anticoagulants are simple alternatives to conventional therapy for patients with acute venous thromboembolism,” the authors wrote.
Results from a related previous trial, AMPLIFY-EXT, showed that after patients completed a standard anticoagulation regimen, recurrent VTE could be safely prevented with an extended course of apixaban.
In an accompanying editorial, Mary Cushman discusses the role of apixaban and other new oral anticoagulants in the treatment of VTE. She reminds physicians that there is still an important role for Vitamin K antagonists and that they will not “disappear from practice.” She lists six “key components” in the selection of a new anticoagulant in VTE patients: patient preference, patient selection, drug interactions, compliance, follow-up, and monitoring. Currently, rivaroxaban (Xarelto, Johnson & Johnson) is the only new oral anticoagulant with an FDA indication for acute VTE.