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A Meta-analysis of 4 Randomized Double-blind Studies

Alexander G. G. Turpie, FRCP; Kenneth A. Bauer, MD; Bengt I. Eriksson, MD, PhD; Michael R. Lassen, MD; for the Steering Committees of the Pentasaccharide Orthopedic Prophylaxis Studies

Arch Intern Med. 2002;162:1833-1840.

Background  Orthopedic surgery remains a condition at high risk of venous thromboembolism (VTE). Fondaparinux, the first of a new class of synthetic selective factor Xa inhibitors, may further reduce this risk compared with currently available thromboprophylactic treatments.

Methods  A meta-analysis of 4 multicenter, randomized, double-blind trials in patients undergoing elective hip replacement, elective major knee surgery, and surgery for hip fracture (N = 7344) was performed to determine whether a subcutaneous 2.5-mg, once-daily regimen of fondaparinux sodium starting 6 hours after surgery was more effective and as safe as approved enoxaparin regimens in preventing VTE. The primary efficacy outcome was VTE up to day 11, defined as deep vein thrombosis detected by mandatory bilateral venography or documented symptomatic deep vein thrombosis or pulmonary embolism. The primary safety outcome was major bleeding.

Results  Fondaparinux significantly reduced the incidence of VTE by day 11 (182 [6.8%] of 2682 patients) compared with enoxaparin (371 [13.7%] of 2703 patients), with a common odds reduction of 55.2% (95% confidence interval, 45.8% to 63.1%; P<.001); this beneficial effect was consistent across all types of surgery and all subgroups. Although major bleeding occurred more frequently in the fondaparinux-treated group (P = .008), the incidence of clinically relevant bleeding (leading to death or reoperation or occurring in a critical organ) did not differ between groups.

Conclusion  In patients undergoing orthopedic surgery, 2.5 mg of fondaparinux sodium once daily, starting 6 hours postoperatively, showed a major benefit over enoxaparin, achieving an overall risk reduction of VTE greater than 50% without increasing the risk of clinically relevant bleeding.

From the Departments of Medicine, Hamilton Health Sciences Corporation—General Division, Hamilton, Ontario (Dr Turpie) and VA Boston Healthcare System and Beth Israel Deaconess Medical Center, Boston, Mass (Dr Bauer); and the Departments of Orthopedics, Sahlgrenska University Hospital/Östra, Göteborg, Sweden (Dr Eriksson) and University Hospital of Copenhagen Hillerød, Hillerød, Denmark (Dr Lassen). All authors served as consultants to Sanofi-Synthelabo and NV Organon. None of the authors has financial conflicts of interest in relation to this study (no equity interests, rights to patents, royalties, or payments from a company with a financial interest in the research).

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