Apixaban, an investigational oral anti blood clotting drug being developed by Bristol-Myers Squibb Company and Pfizer Inc has been found superior to Sanofi-Aventis’ anti-coagulant enoxaparin (Lovenox).
Apixaban showed statistically superior efficacy in dealing with blood clots compared 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 in The Lancet.
Apixaban also showed lower rates of major and non-major bleeding in patients treated compared with those treated with enoxaparin, the study found.
Apixaban is a 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.
“One of the major concerns for orthopedic surgeons using oral anticoagulants for venous thromboembolism prevention in knee surgery is the significant risk of bleeding,” stated Michael Rud Lassen, M.D., Hoersholm Hospital in Copenhagen, Denmark, lead investigator for the study.
Patients undergoing major orthopedic surgery, including total knee replacement, are at high risk for venous thromboembolism.
Venous thromboembolism occurs in 40 to 60 percent of patients undergoing orthopedic 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.
ADVANCE-2, a randomized, double-blind, multicenter, head-to-head trial was designed to evaluate the efficacy and safety of oral, twice daily apixaban 2.5 mg compared with subcutaneous enoxaparin 40 mg once daily, over a 10-to-14 day treatment period for reducing the risk of venous thromboembolism in patients undergoing elective total knee replacement surgery.
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.
When apixaban was compared with enoxaparin, the primary efficacy endpoint occurred in 15.1 percent of patients in the apixaban group and 24.4 percent of patients in the enoxaparin group, demonstrating a statistically significant relative risk reduction for apixaban of 38 percent.
The secondary efficacy outcome of major venous thromboembolism occurred in 1.1 percent of patients in the apixaban group compared with 2.2 percent in the enoxaparin group, demonstrating a statistically significant relative risk reduction for apixaban of 50 percent.
The overall safety profiles of apixaban and enoxaparin were similar in ADVANCE-2.
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.
Deep vein thrombosis causes multiple symptoms including pain, swelling and redness and, more importantly, can progress to pulmonary embolism, which carries the risk of sudden death.
Apixaban is being investigated within the EXPANSE Clinical Trials Program, which is projected to include nearly 60,000 patients worldwide across multiple indications and patient populations and includes a total of nine completed or ongoing, randomized, double-blind Phase III trials, including ADVANCE-2.
The dose and regimen for apixaban were informed by Phase I and II apixaban clinical trial data and data modeling results.
In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialize apixaban, an investigational oral anticoagulant discovered by Bristol-Myers Squibb being studied for the prevention and treatment of a broad range of venous and arterial thrombotic conditions.
Pfizer is world’s top pharmaceutical company.
Bristol-Myers Squibb is a global biopharmaceutical company.