The direct factor Xa inhibitor is indicated for the prevention of venous thromboembolic events (VTE) in adults who have undergone elective hip or knee replacement surgery. It will be marketed as Eliquis.
"The approval of Eliquis gives European orthopaedic surgeons a new option in VTE prevention that is more effective than the current standard of care, enoxaparin 40mg once daily, and importantly, without increasing bleeding," said Dr Michael Rud Lassen of Glostrup Hospital in Copenhagen, Denmark, lead investigator for two Phase III trials of apixaban in orthopaedic surgery.
The randomised double-blind Phase III studies compared oral apixaban 2.5mg twice daily with subcutaneous enoxaparin 40mg once daily. ADVANCE-2 enrolled 3057 patients scheduled for knee replacement surgery and ADVANCE-3 enrolled 5407 patients undergoing hip replacement. Treatment continued for 10–14 days after knee replacement and for 35 days after hip replacement.
The primary efficacy end point in both trials was a composite of asymptomatic or symptomatic deep-vein thrombosis, nonfatal pulmonary embolism, and death from any cause during treatment.
In ADVANCE-2, 1973 patients were eligible for the efficacy analysis. The primary end point occurred in 15% of the apixaban group and 24% of the enoxaparin group, representing a relative risk reduction of 38% for apixaban (95% CI 26—49%; p<0.0001).
Similarly, among the 3866 patients evaluable for efficacy in ADVANCE-3, the primary end point occurred in 1.4% of those who received apixaban compared with 3.9% of those given enoxaparin – a relative risk reduction of 64% (95% CI 46—78%; p<0.001).
Rates of major or clinically relevant non-major bleeding were comparable for apixaban and enoxaparin in both trials.