Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial
Alexander G G Turpie, Kenneth A Bauer, Bengt I Eriksson, Michael R Lassen, for the PENTATHLON 2000 Study Steering Committee*
Department of Medicine, General Division, Hamilton Health Sciences Corporation, Hamilton, Ontario, Canada (Prof A G G Turpie FRCP); Department of Medicine, Veterans Affairs, Boston, USA, and Healthcare System and Beth Israel Deaconess Medical Center, Boston, MA, USA (K A Bauer MD); Orthopaedics Department, Sahlgrenska University Hospital, Östra, Göteborg, Sweden (B I Eriksson MD); Department of Orthopaedics, University Hospital of Copenhagen Hillerød, Hillerød, Denmark (M R Lassen MD)
Correspondence to: Prof Alexander G G Turpie, Hamilton Health Sciences, General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada (e-mail:turpiea@mcmaster.ca)
Summary
Background Elective hip-replacement surgery carries significant risk of venous thromboembolism, despite use of thromboprophylaxis. We aimed to see whether the pentasaccharide fondaparinux, the first drug of a new class of synthetic antithrombotic agents, could reduce this risk to a greater extent than other available treatments. Methods In a double-blind study, we randomly assigned 2275 consecutive patients aged 18 years or older who were undergoing elective hip-replacement surgery to receive postoperative subcutaneous injections of either 2·5 mg fondaparinux once daily or 30 mg enoxaparin twice daily. The primary efficacy outcome was venous thromboembolism to day 11. The main safety outcomes were bleeding and death. Patients were followed up for 6 weeks. Findings We assessed venous thromboembolism to day 11 in 1584 (70%) of 2275 patients. By day 11, venous thromboembolisms were recorded in 48 (6%) of 787 patients on fondaparinux and in 66 (8%) of 797 patients on enoxaparin. The relative reduction in risk was 26·3% (95% CI -10·8 to 52·8, p=0·099). The two groups did not differ in the number of patients who died or in the number who had clinically relevant bleeding. Interpretation In patients undergoing elective hip-replacement surgery, 2·5 mg fondaparinux once daily was not significantly more effective than 30 mg enoxaparin twice daily in reducing risk of venous thromboembolism. However, the lower risk recorded with fondaparinux than enoxaparin was clinically important, with no increase in clinically relevant bleeding. Lancet 2002; 359: 1721-26