Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies.
BACKGROUND
Orthopedic surgery remains a condition at high risk of venous thromboembolism (VTE). Fondaparinux, the first of a new class of synthetic selective factor Xa inhibitors, may further reduce this risk compared with currently available thromboprophylactic treatments.


METHODS
A meta-analysis of 4 multicenter, randomized, double-blind trials in patients undergoing elective hip replacement, elective major knee surgery, and surgery for hip fracture (N = 7344) was performed to determine whether a subcutaneous 2.5-mg, once-daily regimen of fondaparinux sodium starting 6 hours after surgery was more effective and as safe as approved enoxaparin regimens in preventing VTE. The primary efficacy outcome was VTE up to day 11, defined as deep vein thrombosis detected by mandatory bilateral venography or documented symptomatic deep vein thrombosis or pulmonary embolism. The primary safety outcome was major bleeding.


RESULTS
Fondaparinux significantly reduced the incidence of VTE by day 11 (182 [6.8%] of 2682 patients) compared with enoxaparin (371 [13.7%] of 2703 patients), with a common odds reduction of 55.2% (95% confidence interval, 45.8% to 63.1%; P<.001); this beneficial effect was consistent across all types of surgery and all subgroups. Although major bleeding occurred more frequently in the fondaparinux-treated group (P =.008), the incidence of clinically relevant bleeding (leading to death or reoperation or occurring in a critical organ) did not differ between groups.


CONCLUSIONS
In patients undergoing orthopedic surgery, 2.5 mg of fondaparinux sodium once daily, starting 6 hours postoperatively, showed a major benefit over enoxaparin, achieving an overall risk reduction of VTE greater than 50% without increasing the risk of clinically relevant bleeding.
Department of Medicine, Hamilton Health Sciences-General Hospital, 237 Barton, Hamilton, Ontario, Canada L8L 2X2. turpiea@mcmaster.ca
Alexander G G
AG
Turpie
Kenneth A
KA
Bauer
Bengt I
BI
Eriksson
Michael R
MR
Lassen
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D016001:Confidence Intervals; D004311:Double-Blind Method; D017984:Enoxaparin / Q000627:therapeutic use; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D000077425:Fondaparinux; D005593:Fracture Fixation, Internal / Q000009:adverse effects; D006620:Hip Fractures / Q000601:surgery; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D019637:Orthopedic Procedures / Q000009:adverse effects*; D011134:Polysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013923:Thromboembolism / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control*
D000925:Anticoagulants; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D011134:Polysaccharides; D000077425:Fondaparinux