Abstract
Background: The selective factor Xa inhibitor fondaparinux has been shown to be at least as effective and as safe as the low-molecular-weight heparin dalteparin for venous thromboembolism (VTE) prevention after major abdominal surgery (Agnelli GA, et al. Br J Surg, 2005, In press). The benefit of fondaparinux in addition to intermittent pneumatic compression (IPC) in VTE prevention after abdominal surgery has not been evaluated.
Objective: We performed a randomized, double-blind, placebo-controlled, superiority trial to compare the efficacy and safety of fondaparinux in conjunction with IPC versus IPC alone in patients undergoing major abdominal surgery.
Methods: Patients aged at least 40 years undergoing abdominal surgery of at least 45 minutes were included. Patients at highest risk of VTE, requiring pharmacologic prophylaxis in addition to IPC were excluded at the investigator’s discretion. Patients were randomized to receive either fondaparinux 2.5 mg or placebo once daily subcutaneously for 5 to 9 days, starting 6 to 8 hours postoperatively. All patients received IPC. The primary efficacy outcome was the composite of deep-vein thrombosis detected by mandatory bilateral venography, or documented symptomatic deep-vein thrombosis or pulmonary embolism up to day 10. The main safety outcome was major bleeding during the treatment period. A blinded independent committee adjudicated all these outcomes. Follow-up lasted 32 days.
Results: Of the 1309 patients randomized between November 2001 and October 2004 (fondaparinux+IPC, n=650; placebo+IPC, n=659), 842 (64.3%) were evaluable for efficacy. The treatment groups were comparable with regard to VTE risk factors, demographic and surgical characteristics; 82% had at least one VTE risk factor (over and above being at least 40 years old and undergoing abdominal surgery). Fondaparinux significantly reduced the VTE rate from 5.3% (22/418) with placebo to 1.7% (7/424), an odds ratio reduction of 69.8% (95% CI: 27.9 to 87.3; p=0.004). Similarly, fondaparinux significantly reduced the proximal deep-vein thrombosis rate from 1.7% (7/417) to 0.2% (1/423; p=0.037). Major bleeding occurred in 1.6% (10/635) and 0.2% (1/650) of fondaparinux- and placebo-treated patients, respectively (p=0.006). None of the bleeding events were fatal or involved a critical organ.
Conclusions: Fondaparinux combined with IPC was significantly more effective than IPC alone for VTE prevention after major abdominal surgery. Although the bleeding risk was increased with fondaparinux compared with placebo, this risk was low and consistent with that observed in previous fondaparinux studies in surgical patients.
Incidence of deep vein thrombosis after major abdominal surgery in Brisbane