Extended prophylaxis with fondaparinux may be even more beneficial for high-risk patients undergoing hip fracture surgery. We evaluated the efficacy of fondaparinux for thromboprophylaxis in predefined high-risk patients (female gender, age over 75 years, and impaired renal function) in the PENTHIFRA-PLUS trial.
All patients received fondaparinux 2.5 mg once daily for 7 days after surgery, and 656 patients were randomized double-blind to receive placebo or to continue to receive fondaparinux for 19 to 22 additional days. The primary efficacy outcome was venous thromboembolism (VTE) occurring during the double-blind period, defined as deep-vein thrombosis detected by mandatory bilateral venography, or documented symptomatic deep-vein thrombosis or pulmonary embolism.
VTE Rate n/N (Percent)PlaceboFondaparinux77/220 (35.0)3/208 (1.4)*Risk Group:GenderMale11/69 (15.9)0/62 (0.0)Female66/151 (43.7)3/146 (2.1)Age (years)<658/41 (19.5)1/37 (2.7)[65–75[10/36 (27.8)1/48 (2.1)≥ 7559/143 (41.3)1/123 (0.8)Creatinine Clearance (mL/min)<308/15 (53.3)1/14 (7.1)[30–50[23/54 (42.6)0/65 (0.0)[50–80[32/97 (33.0)0/77 (0.0)≥8014/54 (25.9)2/50 (4.0)*
P < 0.001 v Placebo, relative risk reduction 96%The rate of clinically relevant bleeding (fatal bleeding, bleeding in a critical organ, or bleeding leading to reoperation) was similar in both groups.CONCLUSIONS: Female gender, age, and impaired renal function were associated with an increased VTE risk without extended prophylaxis, and extended duration fondaparinux reduced the overall risk of developing VTE by 96%.
VTE prophylaxis with fondaparinux up to 4 weeks after surgery for hip fracture is highly effective in all patients, including patients at high risk of developing VTE, without an increase in clinically relevant bleeding.
A.G. Turpie, Organon Sanofi-Synthelabo, LLC, grant monies.