Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery.
BACKGROUND
Despite thromboprophylaxis, major knee surgery carries a high risk of venous thromboembolism. Fondaparinux, the first of a new class of synthetic antithrombotic agents, may reduce this risk.


METHODS
In a double-blind study, we randomly assigned 1049 consecutive patients undergoing elective major knee surgery to receive subcutaneous doses of either 2.5 mg of fondaparinux once daily or 30 mg of enoxaparin twice daily, with both treatments initiated postoperatively. The primary efficacy outcome was venous thromboembolism up to postoperative day 11, defined as deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or documented symptomatic pulmonary embolism. The primary safety outcome was major bleeding.


RESULTS
The primary efficacy outcome was assessed in 724 patients. The fondaparinux group had a significantly lower incidence of venous thromboembolism by day 11 (12.5 percent [45 of 361 patients]) than the enoxaparin group (27.8 percent [101 of 363 patients]; reduction in risk, 55.2 percent; 95 percent confidence interval, 36.2 to 70.2; P<0.001). Major bleeding (including overt bleeding with a bleeding index of 2 or more) occurred more frequently in the fondaparinux group (P=0.006), but there were no significant differences between the two groups in the incidence of bleeding leading to death or reoperation or occurring in a critical organ.


CONCLUSIONS
In patients undergoing elective major knee surgery, postoperative treatment with 2.5 mg of fondaparinux once daily was significantly more effective in preventing deep-vein thrombosis than 30 mg of enoxaparin twice daily.
Bauer
K A
KA
Department of Medicine, Veterans Affairs Boston Healthcare System and Beth Israel Deaconess Medical Center, MA 02215, USA. kbauer@caregroup.harvard.edu
Eriksson
B I
BI
Lassen
M R
MR
Turpie
A G
AG
D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017558:Elective Surgical Procedures; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077425:Fondaparinux; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D015994:Incidence; D007279:Injections, Subcutaneous; D007717:Knee / Q000601:surgery*; D008297:Male; D011134:Polysaccharides / Q000009:adverse effects / Q000627:therapeutic use; D011183:Postoperative Complications / Q000517:prevention & control*; D011655:Pulmonary Embolism / Q000517:prevention & control*; D013923:Thromboembolism / Q000453:epidemiology / Q000517:prevention & control; D020246:Venous Thrombosis / Q000517:prevention & control*
D017984:Enoxaparin; D005343:Fibrinolytic Agents; D011134:Polysaccharides; D000077425:Fondaparinux