Fondaparinux Reduces DVT After Hip Surgery

May 17, 2002

NEW YORK (MedscapeWire) May 20 — Fondaparinux given prophylactically after hip surgery results in fewer episodes of deep vein thrombosis (DVT) than does the low-molecular-weight heparin (LMWH) enoxaparin, according to the results of a double-blind study published in the May 18 issue of The Lancet. But the trade-off may be higher risk of bleeding, which may be a relative contraindication in patients with coagulation abnormalities.

Fondaparinux, a synthetic pentasaccharide antithrombotic agent that specifically inhibits factor Xa and has no activity against thrombin, is the first in this class. "Drugs that act through specific inhibition of factor Xa, such as fondaparinux, could be more effective than LMWHs in prevention of venous thromboembolism in patients undergoing hip-replacement surgery," write Michael Rud Lassen, from University Hospital Copenhagen in Denmark, and colleagues.

In the European Pentasaccharide Hip Elective Surgery Study (EPHESUS), investigators randomized 2309 patients from 16 European countries who were undergoing elective hip-replacement surgery to once-daily injections of either 2.5 mg of fondaparinux, starting postoperatively, or 40 mg of enoxaparin, starting preoperatively.

By the 11th postoperative day, 4% of patients assigned fondaparinux and 9% of those receiving enoxaparin had DVT ( P<.0001; relative risk reduction, 55.9%). The 2 groups did not differ in survival or frequency of clinically significant bleeding.

In a second study by the same group, 2275 patients from the United States, Canada, and Australia were randomized to prophylaxis with fondaparinux or enoxaparin after hip-replacement surgery. Although there was a 26% relative risk reduction in favor of fondaparinux, it was not statistically significant. Survival and hemorrhagic complications were similar in both groups.

In an accompanying editorial, Henri Bounameaux and Thomas Perneger pooled the results of these 2 trials along with 2 similar trials and found that the overall risk of major bleeding was about 1% greater with fondaparinux than with enoxaparin.

"Fondaparinux may herald a new era in effective prevention of venous thromboembolism, despite the potential for increased bleeding," Bounameaux, from University Hospitals of Geneva, Switzerland, writes in an accompanying commentary. "As with any new drug, fondaparinux should be used cautiously and only in patients who reflect the population of the clinical trials in which the drug was evaluated." He recommends avoiding fondaparinux in fragile patients, such as those who are underweight or who have impaired renal function or any hemorrhagic tendency.

Sanofi-Synthelabo and NV Organon supported these studies.

Lancet. 2002;359:1715-1720, 1710-1711

Reviewed by Gary D. Vogin, MD


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