ORLANDO – Oral apixaban reduced the incidence of major venous thromboembolism after joint replacement surgery by approximately half compared with enoxaparin, with no increased risk of bleeding, investigators have reported.
Of approximately 7,000 patients who underwent thromboprophylaxis after surgery, major VTE occurred in 0.68% of those who had received apixaban, compared with 1.50% who had been given enoxaparin. This was a statistically significant difference, study investigator Gary E. Raskob, Ph.D., said in a press conference at the annual meeting of the American Society of Hematology.
Prevention of major venous thromboembolism (VTE) is "a significant issue in health care in the United States," where the number of knee and hip replacements is expected to increase, said Dr. Raskob, dean of the College of Public Health at the University of Oklahoma Health Sciences Center in Oklahoma City.
Previous studies have demonstrated the potential for an increased risk of bleeding with new anticoagulants. To provide more precise estimates of the incidence of major VTE and safety outcomes, the investigators combined data from two phase III, randomized, double-blind clinical trials of patients who had undergone knee (ADVANCE-2 study) or hip replacement (ADVANCE-3). A total of 8,464 were randomized to receive apixaban, a novel orally administered factor Xa inhibitor (4,236 patients), or enoxaparin (4,228 patients).
Efficacy results related to VTE were based on 3,394 patients in each group. Major VTE occurred in 23 patients in the apixaban group (0.68%), compared with 51 patients in the enoxaparin group (1.50%).
Bleeding results were based on 4,174 apixaban patients and 4,228 enoxaparin patients. Major bleeding occurred in 31 patients in the apixaban group and 32 in the enoxaparin group (0.74% vs. 0.77%). Major bleeding at the surgical site occurred in 26 in the apixaban group and 27 in the enoxaparin group. Overall, major or clinically relevant nonmajor bleeding occurred in 182 apixaban patients and 206 enoxaparin patients (4.4% vs. 4.9%).
The patients received 2.5 mg of apixaban twice daily or 40 mg of enoxaparin once daily. Apixaban was started 12-24 hours after wound closure, and enoxaparin was started approximately 12 hours before surgery and resumed 12-24 hours after wound closure. Both medications were continued for 10-14 days in the knee replacement group and 32-38 days in the hip replacement group. Patients were followed up at 30 days and 60 days after their last doses of either study medication.
Myocardial infarction or stroke occurred in 13 apixaban patients and 10 enoxaparin patients during the course of the study and follow-up period.
Dr. Raskob has served as a consultant or member of the board of directors or advisory committee for multiple companies, including Bristol-Meyers Squibb, Pfizer, Bayer, Johnson & Johnson, Sanofi Aventis, and Daiichi Sankyo.