Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison.
BACKGROUND
Despite use of thromboprophylaxis, elective hip-replacement surgery carries a high risk of venous thromboembolic complications. We aimed to assess the ability of the pentasaccharide fondaparinux, the first of a new class of synthetic antithrombotic agents, to further reduce this risk.


METHODS
In a double-blind study, we randomly assigned 2309 consecutive patients aged 18 years or older who were undergoing elective hip-replacement surgery to once daily, subcutaneous injections of either 2.5 mg fondaparinux, starting postoperatively, or 40 mg enoxaparin, starting preoperatively. The primary efficacy outcome was venous thromboembolism up to day 11, defined as deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or documented symptomatic pulmonary embolism. The main safety outcomes were bleeding and death. The duration of follow-up was 6 weeks. Analysis was per protocol.


RESULTS
We assessed the primary efficacy outcome in 1827 (79%) of 2309 patients. By day 11, venous thromboembolisms were recorded in 37 (4%) of 908 patients assigned to fondaparinux and in 85 (9%) of 919 assigned to enoxaparin (difference -5.2% [95% CI -8.1 to -2.7], p<0.0001). The relative reduction in risk was 55.9% (95% CI 33.1-72.8). The two groups did not differ in frequency of death or clinically relevant bleeding.


CONCLUSIONS
Drugs that act through specific inhibition of factor Xa, such as fondaparinux, could be more effective than low molecular weight heparins in prevention of venous thromboembolism in patients undergoing hip-replacement surgery.
Lassen
Michael Rud
MR
Department of Orthopaedics, University Hospital of Copenhagen Hillerød, DK-3400, Hillerød, Denmark. mirula@fa.dk
Bauer
Kenneth A
KA
Eriksson
Bengt I
BI
Turpie
Alexander G G
AG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip; D004311:Double-Blind Method; D017984:Enoxaparin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077425:Fondaparinux; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D011182:Postoperative Care; D011183:Postoperative Complications / Q000517:prevention & control*; D011300:Preoperative Care; D020246:Venous Thrombosis / Q000517:prevention & control*
D017984:Enoxaparin; D005343:Fibrinolytic Agents; D011134:Polysaccharides; D000077425:Fondaparinux