The study results also showed numerically lower rates of major and clinically relevant non-major bleeding in patients treated with apixaban compared with those treated with enoxaparin. The results did not meet statistical significance.
Apixaban is a novel, oral, highly selective Factor Xa inhibitor, part of a class of agents being studied for their potential to prevent and treat blood clots in the veins and arteries. Results of Adance-2 were first presented in July 2009 at the 22nd Congress of the International Society on Thrombosis and Haemostasis in Boston.
In the study, of the 3,221 patients from 27 countries (Europe, Asia/Pacific, Latin America, Africa) enrolled in the study, 1,973 patients were eligible for the analysis of the primary efficacy endpoint defined as the composite of asymptomatic and symptomatic deep vein thrombosis, non-fatal pulmonary embolism, and death from any cause during study treatment. The statistical plan for the study required testing non-inferiority of Apixaban before testing for superiority.
When Apixaban was compared with Enoxaparin, the primary efficacy endpoint occurred in 15.1% of patients in the Apixaban group and 24.4% of patients in the Enoxaparin group, demonstrating relative risk reduction for Apixaban of 38%.
Additionally, the secondary efficacy outcome of major venous thromboembolism occurred in 1.1% of patients in the Apixaban group compared with 2.2% in the Enoxaparin group, demonstrating a statistically significant relative risk reduction for Apixaban of 50%.
The overall safety profiles of Apixaban and Enoxaparin were similar in Advance-2. During the treatment and follow-up periods, liver alanine transaminase (ALT) and liver aspartate transaminase (AST) elevations greater than three times the upper limit of normal were reported in 2% of patients in the Apixaban and Enoxaparin groups. Discontinuations due to adverse events in the Apixaban and Enoxaparin patient groups were similar.
Michael Rud Lassen, lead investigator for the study, said: “One of the major concerns for orthopedic surgeons using oral anticoagulants for venous thromboembolism prevention in knee surgery is the significant risk of bleeding. We are encouraged by the Advance-2 data, which demonstrated better antithrombotic effect and comparable bleeding rates for Apixaban compared with Enoxaparin.”