Fondaparinux 2.5 mg once daily significantly reduced the risk of venous thromboembolism compared to enoxaparin 30 mg twice daily after elective major knee surgery (12.5% vs 27.8%; P<0.001).
RCT (n=1,049)
Double-blind
Does fondaparinux reduce venous thromboembolism in patients undergoing elective major knee surgery compared to enoxaparin?
Fondaparinux 2.5 mg once daily is more effective than enoxaparin 30 mg twice daily for preventing venous thromboembolism after elective major knee surgery, though it is associated with an increased risk of major bleeding.
Effect estimate: Risk reduction 55.2% (95% CI 36.2-70.2)
Absolute Event Rate: 12.5% vs 27.8%
p-value: p=<0.001
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 et al. (2001) conducted an RCT in Elective major knee surgery (n=1,049). Fondaparinux vs. Enoxaparin 30 mg twice daily subcutaneously was evaluated on Venous thromboembolism up to postoperative day 11 (deep-vein thrombosis by venography, symptomatic deep-vein thrombosis, or symptomatic pulmonary embolism) (Risk reduction 55.2%, 95% CI 36.2-70.2, p=<0.001). Fondaparinux 2.5 mg once daily significantly reduced the risk of venous thromboembolism compared to enoxaparin 30 mg twice daily after elective major knee surgery (12.5% vs 27.8%; P<0.001).