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Evidence summaries

Fondaparinux in the Prevention of Venous Thromboembolism after Surgery

Postoperative fondaparinux is more effective than perioperative enoxaparin in major orthopaedic surgery in the prevention of venous thromboembolism in high-risk patients but appears to increase major bleeding. Level of evidence: "A"

A meta-analysis 1 of 4 RCTs (n=7 344) in patients undergoing elective hip replacement, elective major knee surgery, and surgery for hip fracture compared subcutaneous fondaparinux sodium 2.5 mg once-daily starting 6 hours after surgery with enoxaparin regimens in preventing venous thromboembolism (VTE). Primary outcome was VTE up to day 11 defined as deep vein thrombosis (DVT) on mandatory bilateral venography or documented symptomatic DVT or pulmonay embolism. Fondaparinux reduced the incidence of VTE by day 11 compared with enoxaparin (6.8% vs. 13.7%, P<0.001). This beneficial effect was consistent across all types of surgery and all subgroups. Major bleeding occurred more frequently in the fondaparinux group (p=0.008), but the incidence of clinically relevant bleeding (leading to death or reoperation or occurring in a critical organ) did not differ between groups.

These 4 studies were reanalyzed2 using the efficacy end point established by the ACCP Consensus Conference on Antithrombotic Therapy (any proximal deep-vein thrombosis, symptomatic proven deep-vein thrombosis or pulmonary embolism, or fatal pulmonary embolism) and that established by the European CPMP (any proximal deep-vein thrombosis, symptomatic proven pulmonary embolism, or death from any cause). The incidences of efficacy end points with enoxaparin and fondaparinux were 3.3% and 1.7% (p<0.001) according to the ACCP definition, and 3.9% and 2.1% (p<0.001) according to the CPMP definition.

Two technology assessment reports 3 4 on fondaparinux for post-operative venous thrombosis prophylaxis were abstracted in the Health Technology Assessment Database. Fondaparinux belongs to a new class of synthetic antithrombotic agents called pentasaccharides. Fondaparinux was more efficacious in phase III trials comparing fondaparinux and enoxaparin for the prevention of deep vein thrombosis in patients undergoing major orthopaedic surgery. The overall relative risk reduction in four trials was 25% to 56%. The overall major bleeding rate associated with fondaparinux was higher than the rate associated with enoxaparin, although the statistical significance of this difference is inconsistent. Fondaparinux is administered over a shorter course than low molecular weight heparin (LMWH) and may lead to some reduction in service use.

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References

  • Turpie AG, Bauer KA, Eriksson BI et al. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med 2002;162(16):1833-40. [PubMed]
  • Turpie AG, Bauer KA, Eriksson BI, Lassen MR. Superiority of fondaparinux over enoxaparin in preventing venous thromboembolism in major orthopedic surgery using different efficacy end points. Chest 2004 Aug;126(2):501-8. [PubMed]
  • Garces K, Mamdani M. Fondaparinux for post-operative venous thrombosis prophylaxis. Ottawa: Canadian Coordinating Office for Health Technology Assessment (CCOHTA) 2002:4. www.ccohta.ca [HTA-32002000900 ]. [DARE]
  • Fondaparinux for venous thromboembolism. Birmingham: National Horizon Scanning Centre (NHSC) 2001:5 [HTA-32002000849 ]. [DARE]

Primary/Secondary Keywords