Apixaban, an oral anticoagulant being developed by Bristol-Myers Squibb Company and Pfizer Inc, was statistically superior to 40 mg once daily enoxaparin in reducing the incidence of venous thromboembolism in patients undergoing elective total knee replacement surgery, according to the ADVANCE-2 study results published today in The Lancet. 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. These 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 ADVANCE-2 were first presented in July 2009 at the 22nd Congress of the International Society on Thrombosis and Haemostasis in Boston.

Patients undergoing major orthopaedic surgery, including total knee replacement, are at high risk for venous thromboembolism. In fact, venous thromboembolism occurs in 40 to 60 per cent of patients undergoing orthopaedic surgery who do not receive preventive care. With an estimated 400,000 people worldwide undergoing total knee replacement surgery each year, the threat of venous thromboembolism and its associated morbidity and mortality risk represent a growing challenge to physicians.

"One of the major concerns for orthopedic surgeons using oral anticoagulants for venous thromboembolism prevention in knee surgery is the significant risk of bleeding," said Michael Rud Lassen, Hoersholm Hospital in Copenhagen, Denmark, lead investigator for the study. "We are encouraged by the ADVANCE-2 data, which demonstrated better antithrombotic effect and comparable bleeding rates for apixaban compared with enoxaparin."

Venous thromboembolism encompasses two serious conditions: deep vein thrombosis, a blood clot in a vein, usually in the leg that partially or totally blocks the flow of blood; and pulmonary embolism, a blood clot blocking a vessel in the lungs.