The Pharmaceutical Journal Vol 267 No 7176 p767-773
1 December 2001

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New antithrombotic more effective than enoxaparin in surgical patients

Fondaparinux, a new antithrombotic agent, is more effective than enoxaparin in preventing venous thromboembolism in patients who have had hip fracture surgery, a new study shows. It is also more effective in patients who have undergone elective major knee surgery.

Fondaparinux, a synthetic pentasaccharide, is the first in a new class of antithrombotic agents that selectively inhibit activated factor Xa, a blood coagulation factor. Fondaparinux is structurally related to the antithrombin-binding site of heparin. Sanofi-Synthelabo, manufacturer of fondaparinux, hopes to launch the drug in the United Kingdom during the first half of next year.

Dr Bengt Eriksson, Sahlgrenska University Hospital-Östra, Sweden, analysed 1,250 patients undergoing hip-fracture surgery who had been randomly assigned to receive subcutaneous doses of either fondaparinux 2.5mg once daily (intended as postoperative treatment) or enoxaparin 40mg once daily (intended to be initiated preoperatively) for at least five days.

The researchers found that the incidence of venous thromboembolism by day 11 postoperatively was 8.3 per cent (52 out of 626 patients) in the fondaparinux group and 19.1 per cent (119 out of 624 patients) in the enoxaparin group (P<0.001). The researchers say that the incidence found for the enoxaparin group is consistent with the results of previous studies of enoxaparin after hip-fracture surgery (New England Journal of Medicine 2001;345:1298).

In a second study, Dr Kenneth Bauer, Beth Israel Deaconess Medical Centre, Boston, and colleagues assessed 724 patients undergoing elective major knee surgery who had been randomly assigned to receive subcutaneous doses of either fondaparinux 2.5mg once daily or enoxaparin 30mg twice daily, both given postoperatively. They say that the patients treated with fondaparinux had a lower incidence of venous thromboembolism 11 days after surgery than those in the enoxaparin group, 12.5 per cent versus 27.8 per cent, respectively. Major bleeding occurred more frequently in the fondaparinux group. However, there were no significant differences between the two groups in the incidence of bleeding leading to death or re-operation or occurring in a critical organ, they say (ibid, p1305).

A spokesman for Aventis Pharma, manufacturer of enoxaparin, told The Journal that enoxaparin is licensed in the UK for administration 12 hours before surgery for patients at high risk of deep vein thrombsis. In the study carried out by Dr Bengt Eriksson and colleagues, 74.4 per cent of patients (464 out of 624) receiving enoxaparin received it postoperatively because of early surgery after admission to hospital or planned local anaesthesia. "This delay may have reduced the efficacy of enoxaparin because the timing of administration of thromboprophylaxis has a crucial impact on efficacy," he said. The spokesman also stated that major bleeding is of great concern to orthopaedic surgeons and may outweigh fondaparinux's potentially superior ability to reduce venographically detected deep vein thrombosis.

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