As evidence of the long-term risk of VTE after orthopedic surgery builds, the strategy of extended prophylaxis is increasing. In 2 phase III trials we analyzed the risk of developing VTE and the efficacy of fondaparinux for the prevention of VTE up to 4 weeks after surgery for hip fracture.
In the PENTHIFRA trial, 1250 patients were randomized double-blind to receive either fondaparinux 2.5 mg or enoxaparin 40 mg once daily up to 11 days after surgery. In the PENTHIFRA-PLUS trial all patients received fondaparinux 2.5 mg once daily for 7 days postoperatively, and 656 patients were randomized double-blind to receive placebo or to continue to receive fondaparinux for 19 to 22 additional days. To assess the risk of VTE, we analyzed the occurrence of symptomatic VTE in each trial up to 4 weeks after surgery.
In the PENTHIFRA trial, a total of 22 out of 30 (73 percent) symptomatic VTE occurred between days 12 and 32. In the PENTHIFRA-PLUS trial, only 1 symptomatic VTE occurred in the fondaparinux group and 9 occurred in the placebo group (relative risk reduction 88.8 percent, P = 0.021; x represents symptomatic events):
Day after surgery78910111213141516171819202122232425PlaceboxxxxxxxxxFondaparinuxxCONCLUSIONS: The risk of VTE persists for at least four weeks after hip fracture surgery, and extended duration fondaparinux is highly effective in reducing VTE events.
The reduction in risk with fondaparinux, coupled with the previously demonstrated superiority of fondaparinux compared with enoxaparin, adds extended prophylaxis with fondaparinux to the therapeutic options for thromboprophylaxis after hip repair surgery.
A.G. Turpie, Organon Sanofi-Synthelabo, LLC, Grant monies.