Extended Thromboprophylaxis with Fondaparinux after Major Orthopedic Surgery of the Lower Limbs: The EXPERT Study.

Background: The benefit-to-risk ratio of extended fondaparinux therapy was demonstrated in patients undergoing hip fracture surgery, but not in patients undergoing major joint arthroplasty. In addition, no data on the use of fondaparinux in patients in whom a continuous neuraxial/deep peripheral nerve blockade is performed are available.

Objective: The EXPERT trial was an open-label, international study in patients undergoing major orthopedic surgery designed to evaluate the overall efficacy and safety of 2.5 mg fondaparinux when (I) given daily for 4±1 weeks after surgery, and (II) a “therapeutic window” is applied due to concomitant use of a neuraxial/deep peripheral indwelling catheter.

Patients/Methods: Patients undergoing major orthopedic surgery received once-daily subcutaneous 2.5 mg fondaparinux starting post-surgery for 4±1 weeks. In patients with a neuraxial/deep peripheral indwelling catheter, one of the planned doses of fondaparinux was omitted, the catheter was removed 36 hours after the previous fondaparinux dose, and the next fondaparinux dose administered 12 hours after catheter removal. The primary endpoints were symptomatic venous thromboembolism (VTE) and major bleeding 5±1 weeks after surgery.

Results: 5704 patients (mean age ± SD: 66.1 ± 11.9 years) were recruited into the intention-to-treat (ITT) population between July 2003 and October 2004. A neuraxial/deep peripheral indwelling catheter was placed in 1630 (28.6%) of them. They underwent surgery for total hip replacement (51.6%, n=2941), total knee replacement (39.7%, n=2263), hip fracture (6.2%, n=353), or other indications (2.6%, n=148). Fondaparinux was given for a median of 35 (range: 1–105) days. In the ITT population, the rate of adjudicated confirmed symptomatic VTE was 1.0% (54/5387). It was 0.8% (13/1535) in patients with catheter and 1.1% (41/3852) in patients without catheter, with an odds ratio of 0.79 (90% CI: 0.47 to 1.34; p=0.47) in favor of patients with a catheter. The upper limit of the 90% CI was below the predetermined criterion of 1.75 for the non-inferiority of patients with a catheter versus patients without a catheter. Comparable results were observed in the per-protocol population. The overall rate of major bleeding was 0.8% (42/5382). It was 0.9% (35/3850), and 0.5% (7/1532) in patients with and without catheter, respectively. No spinal or perineural hematomas occurred. At 5±1 weeks, 23 (0.40%) patients had died.

Conclusions: 2.5 mg fondaparinux given daily for 4±1 weeks after major orthopedic surgery was both effective and safe in routine practice. This high benefit-to-risk ratio was maintained in patients in whom a 48-hour “therapeutic window” was applied due to placement of a neuraxial/deep peripheral indwelling catheter.