The safety and efficacy of extended thromboprophylaxis with fondaparinux after major orthopedic surgery of the lower limb with or without a neuraxial or deep peripheral nerve catheter: The EXPERT study

BACKGROUND: The benefit-risk ratio of extended fondaparinux therapy has not been assessed in patients undergoing major lower limb joint arthroplasty. Few data on the concomitant use of fondaparinux and continuous neuraxial or deep peripheral nerve blockade are available. We performed a prospective intervention study in patients undergoing major orthopedic surgery primarily designed to assess the efficacy of fondaparinux when drug administration was withheld for 48 h to permit removal of a neuraxial or deep peripheral nerve catheter. The safety and efficacy of extended fondaparinux therapy for the prevention of venous thromboembolism were also evaluated. METHODS: Patients received a daily subcutaneous injection of 2.5 mg fondaparinux for 3 to 5 wk postoperatively. In patients with a neuraxial or deep peripheral nerve catheter, the catheter was removed 36 h after the last fondaparinux dose. The next fondaparinux dose was administered 12 h after catheter removal. The primary end points were symptomatic venous thromboembolism and major bleeding up to 4-6 wk after surgery. RESULTS: We recruited 5704 patients. A neuraxial or deep peripheral nerve catheter was inserted in 1553 (27%) patients and 78 (1.4%) patients, respectively. The rate of venous thromboembolism was 1.0% (54 of 5387). There was no difference between patients without (1.1%) or with (0.8%) a catheter (the upper limit of the 95% confidence interval of the odds ratio, 1.49, being below the predetermined noninferiority margin of 1.75). The incidence of major bleeding was 0.8% (42 of 5382). No neuraxial or perineural hematoma was reported. CONCLUSIONS: Once-daily subcutaneous injection of 2.5 mg fondaparinux given for 3 to 5 wk was effective and safe for prevention of venous thromboembolism after major orthopedic surgery. Temporary discontinuation of fondaparinux for 48 h permitted safe removal of a neuraxial or deep peripheral nerve catheter without decreasing thromboprophylatic efficacy.