Clinical Question: Is fondaparinux or enoxaparin better at preventing important venous thromboembolic events following orthopedic surgery?
Setting: Inpatient (any location)
Study Design: Meta-analysis (randomized controlled trials)
Synopsis: A variety of outcomes are used in studies of venous thromboembolism prophylaxis for surgical patients, ranging from the disease-oriented (asymptomatic radiographically detected deep venous thrombosis [DVT]) to the patient-oriented (death from any cause). Four studies compared fondaparinux with enoxaparin in patients undergoing major orthopedic surgery, and each included asymptomatic distal DVTs in its combined outcome. Because these are of questionable clinical significance, the authors of this study reanalyzed the data using a more patient-oriented combined outcome. All four studies included adults scheduled for elective major hip or knee surgery, or surgery for a proximal femoral fracture, and patients were randomized to fondaparinux in a dosage of 2.5 mg once daily or enoxaparin. In two studies, enoxaparin was given in a 30-mg dosage twice daily starting 12 to 24 hours before surgery; in the other two studies, 40 mg was given once daily starting 12 hours before surgery. The four studies included a total of 7,344 patients who were followed postoperatively for 11 days. Outcomes were assessed by a committee blinded to treatment assignment, and the four studies were homogenous, but allocation concealment was not described.
The two outcomes assessed in this reanalysis were (1) symptomatic and asymptomatic proximal DVT, any symptomatic DVT or pulmonary embolism (PE), and any fatal PE; and (2) symptomatic and asymptomatic proximal DVT, symptomatic PE, and death from any cause. Both outcomes were less common in patients receiving fondaparinux (1.7 versus 3.3 percent for the first outcome and 2.1 versus 3.9 percent for the second). Both differences were statistically significant, with numbers needed to treat of 62 and 56, respectively. When considering subgroups by the type of surgery, the difference was still significant for hip fracture surgery and elective major knee surgery, but not for elective hip replacement surgery. The study was not powered to detect a significant difference in symptomatic events alone in the two treatment groups.
Bottom Line: Fondaparinux prevents more clinically important venous thromboembolic events than enoxaparin in patients undergoing major orthopedic surgery. (Level of Evidence: 1a)