Structured abstract
Question
Compared to perioperative enoxaparin, does postoperative fondaparinux decrease the incidence of postoperative venous thromboembolism (VTE)?
Design
Meta-analysis of four phase III multicentre, randomized, parallel-group, double-blind clinical trials designed a priori by one group of investigators to permit meta-analysis.
Setting
Three hundred and seventy-five centres in Argentina, Australia and New Zealand, Europe, North America, and South Africa.
Patients
Seven thousand, three hundred and fortyfour patients ≥18 yr of age (mean age 68 yr, 60% women) undergoing elective total hip arthroplasty (two studies), elective knee arthroplasty (one study), or hip fracture surgery (one study). Exclusion criteria were contraindications to anticoagulation therapy (active or increased risk for bleeding, planned use of indwelling intrathecal or epidural catheter, more than two attempts at neuraxial anesthesia, or hypersensitivity), addiction disorders, renal dysfunction, or required anticoagulant therapy for chronic comorbid disease. Seven thousand, two hundred and thirtyseven patients received at least one dose of the study drug and 5,385 patients completed the study. One thousand, nine hundred and fifty-nine patients (986 in the fondaparinux group; 973 in the enoxaparin group) did not receive the study drug, did not undergo the scheduled surgery, or did not undergo adequate venography for diagnosis of deep vein thrombosis (DVT).
Intervention
Three thousand, six hundred and sixty-eight patients were allocated to receive sc fondaparinux 2.5 mg once daily, beginning six hours after surgery. Three thousand, six hundred and seventy-six patients were allocated to either sc enoxaparin 30 mg twice daily, beginning 12 to 24 hr after surgery (North American regimen, two studies) or sc enoxaparin 40 mg once daily, beginning 12 hr before surgery with a second injection 12 to 24 hr after surgery (European regimen, two studies).
Main outcomes
The primary efficacy outcome was the combined endpoint of 11-day DVT or pulmonary embolus. The primary safety outcome was major bleeding. Death, minor bleeding, transfusion requirements, thrombocytopenia, and other adverse events were evaluated also. Efficacy outcomes were adjudicated by a blinded committee.
Main results
Analysis was per protocol. Patient and surgical characteristics were similar between groups. The incidence of VTE was lower in the fondaparinux group (182/2682) compared to the enoxaparin group (371/2703; P < 0.001; Table). Major bleeding events were more frequent in the fondaparinux group (96/3616) than in the enoxaparin group (63/3621; P= 0.008). The incidences of death, minor bleeding, and other adverse events did not differ between the two groups.
Conclusion
Compared to enoxaparin, fondaparinux reduced the incidence of VTE but increased the incidence of major bleeding events.
Funding
Sanofi-Synthelabo (Paris, France) and NV Organon (Oss, the Netherlands).
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References
Turpie AG, Bauer KA, Eriksson BI, Lassen MR, for the Steering Committees of the Pentasaccharide Orthopedic Prophylaxis Studies. 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: 1833–40.
Turpie AG, Bauer KA, Eriksson BI, Lassen MR;PEN-TATHALON 2000 Study Steering Committee. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised doubleblind trial. Lancet 2002; 359: 1721–6.
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References
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Hull RD, Pineo GF, Stein PD, et al. Extended out-ofhospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med 2001; 135: 858–69.
Turpie AG, Bauer KA, Eriksson BI, Lassen MR, for the Steering Committees of the Pentasaccharide Orthopedic Prophylaxis Studies. 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: 1833–40.
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Hardy, J.F., Lee, H.N. Best evidence in anesthetic practice Prevention: Fondaparinux is better than enoxaparin for prevention of major venous thromboembolism after orthopedic surgery. Can J Anesth 50, 764–766 (2003). https://doi.org/10.1007/BF03019370
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DOI: https://doi.org/10.1007/BF03019370