Venous thromboembolism prophylaxis: role of factor xa inhibition by fondaparinux

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.