Fondaparinux (
Arixtra, GlaxoSmithKline, Philadelphia, PA.) is the first synthetic selective
factor Xa inhibitor. A worldwide phase III program, that consists of four randomized, double-blind trials, in patients who underwent surgery for hip fracture, and elective hip replacement and elective major knee surgery was conducted to compare the benefit-to-risk ratio of a subcutaneous 2.5 mg once-daily regimen of
fondaparinux starting postoperatively versus
enoxaparin in preventing
venous thromboembolism. The overall incidence of
venous thromboembolism up to day 11 was reduced from 13.7% in the
enoxaparin group, to 6.8% in the
fondaparinux group, with a relative risk reduction of 50.6% in favor of
fondaparinux (95% confidence interval: 40.9% to 59.1%, p<0.001). The overall incidence of clinically relevant
bleeding was low and did not differ between the two groups. The benefit of
fondaparinux was consistent across all types of surgery and all subgroups. The further randomized, double-blind PENTHIFRA-PLUS trial showed that extending
fondaparinux prophylaxis from one to four weeks after hip fracture surgery was well tolerated and, compared to one-week
fondaparinux, dramatically reduced delayed
venous thromboembolism events from 35.0% to 1.4% (p<0.001). Four-week
fondaparinux could become the standard thromboprophylaxis after hip fracture surgery.
Fondaparinux is the first selective
factor Xa inhibitor approved for use in thromboprophylaxis after
orthopedic surgery.