37 – Are there differences between various injectable agents for pharmacological VTE prophylaxis with regard to efficacy and safety profile?

Sahar Hamdi, Rudolf W. Poolman, Cassius I. Ochoa Chaar.

Response/Recommendations: Compared to low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH), fondaparinux appears to have a better efficacy profile for prevention of venous thromboembolism (VTE) following orthopaedic procedures. Based on current evidence, there appears to be no difference in the safety profile of the different injectable pharmacological agents in terms of perioperative bleeding risk.

Strength of Recommendation: Moderate.

Rationale: Several studies evaluating patients undergoing total hip arthroplasty (THA) have shown that using subcutaneous injection of fondaparinux for VTE prophylaxis is more effective than subcutaneous injection of LMWH or UFH in decreasing postoperative VTE1–4. The relative reduction of postoperative VTE was approximately 50% with fondaparinux 2.5 mg subcutaneous (SC) injection compared to enoxaparin based on a meta-analysis of 4 randomized trials2. Studies with smaller sample sizes suggested that fondaparinux and enoxaparin were equally effective, but the studies may have been underpowered5,6. Shorr et al., used a large billing database and examined patients undergoing THA, total knee arthroplasty (TKA), and hip fracture surgery and showed that the use of fondaparinux was not only associated with lower VTE compared to enoxaparin, dalteparin, and UFH but was also more cost effective1. UFH, enoxaparin, and other LMWH seem to be equally effective in terms of prevention of VTE. The studies and corresponding incidences of VTE with various injectable agents are summarized in the appendix (Table 1). Some studies suggest that ultra-LMWH such as semuloparin and bemiparin, which exhibit more selective inhibition of factor Xa, are more effective than other LMWH including enoxaparin7–9. Another potential advantage of ultra-LMWH is a better safety profile7,8, which has not been proven by clinical studies reviewed and remains elusive. In fact, most of the prospective studies reviewed showed no significant differences in bleeding risk between the various injectable agents. The study by Shorr et al., consisting of more than 120,000 cases from a large database suggested that dalteparin was least associated with bleeding1. Bleeding rates reported in various studies are summarized in the appendix (Table 2). There was no difference in mortality after orthopaedic surgery in any of the studies using the various injectable agents for pharmacological VTE prophylaxis.

Based on the available data, it appears that fondaparinux may have better efficacy profile for prevention of VTE after orthopaedic procedures, compared to other injectable agents. However, the data is not conclusive and at this point, it appears that most injectable agents have proven efficacy for reduction of VTE after surgical procedures. Clinicians should decide on the choice of injectable agents based on the clinical situation for each patient taking into account the available data.


1.         Shorr AF, Sarnes MW, Peeples PJ, Stanford RH, Happe LE, Farrelly E. Comparison of cost, effectiveness, and safety of injectable anticoagulants used for thromboprophylaxis after orthopedic surgery. Am J Health Syst Pharm. 2007;64(22):2349-2355. doi:10.2146/ajhp070178

2.         Turpie AGG, Bauer KA, Eriksson BI, Lassen MR. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med. 2002;162(16):1833-1840. doi:10.1001/archinte.162.16.1833

3.         Lassen MR, Bauer KA, Eriksson BI, Turpie AGG, European Pentasaccharide Elective Surgery Study (EPHESUS) Steering Committee. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet. 2002;359(9319):1715-1720. doi:10.1016/S0140-6736(02)08652-X

4.         Sasaki S, Miyakoshi N, Matsuura H, Saitoh H, Kudoh D, Shimada Y. Prospective randomized controlled trial on the effect of fondaparinux sodium for prevention of venous thromboembolism after hip fracture surgery. J Orthop Sci. 2009;14(5):491-496. doi:10.1007/s00776-009-1365-4

5.         Ishibe M, Kariya S. Deep venous thrombosis after mini-posterior total hip arthroplasty in Japanese patients. Hip Int. 2011;21(6):684-687. doi:10.5301/HIP.2011.8825

6.         Yokote R, Matsubara M, Hirasawa N, Hagio S, Ishii K, Takata C. Is routine chemical thromboprophylaxis after total hip replacement really necessary in a Japanese population? J Bone Joint Surg Br. 2011;93(2):251-256. doi:10.1302/0301-620X.93B2.25795

7.         Navarro-Quilis A, Castellet E, Rocha E, Paz-Jiménez J, Planès A, Bemiparin Study Group in Knee Arthroplasty. Efficacy and safety of bemiparin compared with enoxaparin in the prevention of venous thromboembolism after total knee arthroplasty: a randomized, double-blind clinical trial. J Thromb Haemost. 2003;1(3):425-432. doi:10.1046/j.1538-7836.2003.00142.x

8.         Kakkar VV, Howes J, Sharma V, Kadziola Z. A comparative double-blind, randomised trial of a new second generation LMWH (bemiparin) and UFH in the prevention of post-operative venous thromboembolism. The Bemiparin Assessment group. Thromb Haemost. 2000;83(4):523-529.

9.         Lassen MR, Dahl OE, Mismetti P, Destrée D, Turpie AGG. AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery–TREK: a dose-ranging study. J Thromb Haemost. 2009;7(4):566-572. doi:10.1111/j.1538-7836.2009.03301.x