Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison

Lassen, Michael R.; Bauer, Kenneth A.; Eriksson, Bengt I.; Turpie, Alexander G. G.

doi:10.1016/s0140-6736(02)08652-x

Cited by 418 publications

(310 citation statements)

References 24 publications

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“…Two venography-based studies have shown that fondaparinux is effective for prevention of VTE in patients undergoing total hip replacement. 46,47 In a European study, fondaparinux given at the dose of 2.5 mg once daily starting 4 to 8 hours after surgery significantly reduced the incidence of DVT from 9% to 4% in comparison with enoxaparin given at a dose of 40 mg once daily starting 12 hours before surgery. The rate of proximal DVT also was significantly reduced by fondaparinux from 2% to 1%.…”

Section: Elective Hip Replacementmentioning

confidence: 99%

“…The rate of proximal DVT also was significantly reduced by fondaparinux from 2% to 1%. 46 In a North American trial, the same fondaparinux regimen was compared with enoxaparin 30 mg twice daily started 12 to 24 hours after surgery. 47 In this study, the rate of overall VTE was reduced from 8% to 6% (PϭNS) in the fondaparinux group.…”

Section: Elective Hip Replacementmentioning

confidence: 99%

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Prevention of Venous Thromboembolism in Surgical Patients

2004

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Abstract-Venous thromboembolism (VTE) is a common complication of surgical procedures. The risk for VTE in surgical patients is determined by the combination of individual predisposing factors and the specific type of surgery. Prophylaxis with mechanical and pharmacological methods has been shown to be effective and safe in most types of surgery and should be routinely implemented. For patients undergoing general, gynecologic, vascular, and major urologic surgery, low-dose unfractionated heparin or low-molecular-weight heparin (LMWH) are the options of choice. For low-risk urologic surgery, early postoperative mobilization of patients is the only intervention warranted. For higher-risk patients, including those undergoing elective hip or knee replacement and surgery for hip fracture, vitamin K antagonists, LMWH, or fondaparinux are recommended. For patients undergoing neurosurgery, graduated elastic stockings are effective and safe and may be combined with LMWH to further reduce the risk of VTE. The role of prophylaxis is less defined in patients undergoing elective spine surgery, as well as laparoscopic and arthroscopic surgery. A number of issues related to prophylaxis of VTE after surgery deserve further clarification, including the role of screening for asymptomatic deep vein thrombosis, the best timing for initiation of pharmacological prophylaxis, and the optimal duration of prophylaxis in high-risk patients. Key Words: venous thromboembolism Ⅲ deep vein thrombosis Ⅲ pulmonary embolism Ⅲ heparin Ⅲ low-molecular-weight heparin Ⅲ vitamin K antagonists

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Section: Elective Hip Replacementmentioning

confidence: 99%

Section: Elective Hip Replacementmentioning

confidence: 99%

Prevention of Venous Thromboembolism in Surgical Patients

2004

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“…Platelet count data were reviewed for the 37 SRA-positive patients, with the last available platelet count value obtained a median (interquartile range) of 8 (7,8) days after the first administration of study drug. One of these 37 SRA-positive patients met our criteria for clinical HIT (Fig.…”

Section: Patient With Clinical Hitmentioning

confidence: 99%

Anti‐PF4/heparin antibody formation postorthopedic surgery thromboprophylaxis: the role of non‐drug risk factors and evidence for a stoichiometry‐based model of immunization

Warkentin

Cook

Marder

et al. 2010

Journal of Thrombosis and Haemostasis

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To cite this article: Warkentin TE, Cook RJ, Marder VJ, Greinacher A. Anti-PF4/heparin antibody formation postorthopedic surgery thromboprophylaxis: the role of non-drug risk factors and evidence for a stoichiometry-based model of immunization. J Thromb Haemost 2010; 8: 504-12.Summary. Background: Heparin-induced thrombocytopenia is an antibody-mediated disorder exhibiting variable frequency in different clinical settings. Antibodies recognize PF4/heparin complexes formed at optimal stoichiometric molar ratios. Objective: To identify clinical factors influencing risk of anti-PF4/heparin immunization. Patients/methods: We performed observational studies and exploratory analyses of the frequency of anti-PF4/heparin antibody formation in 6324 patients who received enoxaparin or fondaparinux in four randomized controlled trials of postorthopedic surgery thromboprophylaxis. Variables included surgery type (knee vs. hip), timing of first anticoagulant dose (pre-vs. postsurgery), circumstances of surgery (elective vs. hip fracture), anticoagulant (enoxaparin vs. fondaparinux) and body-mass index (BMI). We applied a stoichiometry-based model that predicts immunization risk based on expected differences in PF4/anticoagulant ratios in different settings, and specifically used this model to predict the effect of increasing BMI quartiles upon relative risk (RR) of immunization for fondaparinux vs. enoxaparin. Results: Anti-PF4/heparin immunization was more frequent after knee vs. hip surgery (particularly for enoxaparin), and when enoxaparin was given post-rather than pre-elective surgery; however, the opposite occurred with hip fracture surgery, that is, antibody formation was more frequent when enoxaparin or fondaparinux was given presurgery. The RR of immunization for fondaparinux vs. enoxaparin decreased significantly for increasing BMI quartiles, an effect predominantly because of increasing immunization with enoxaparin at increasing BMI quartiles. Conclusions: Several non-drug factors -including type and circumstances of surgery, timing of first anticoagulant dose and BMI -influence risk of anti-PF4/heparin antibody formation, consistent with a stoichiometry-based immunization model of PF4 and anticoagulant ratios occurring during the early perioperative period.

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“…It has been developed to provide a selective anticoagulant effect and to overcome some side effects of LMWH such as allergic reactions [5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of venous thromboembolism prophylaxis with fondaparinux or low molecular weight heparin in a large cohort of consecutive patients undergoing major orthopaedic surgery – findings from the ORTHO‐TEP registry

Donath¹,

Lützner

Werth³

et al. 2012

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THE TOPIC• Patients undergoing major orthopaedic surgery are at high risk of venous thromboembolism.• Medical thromboprophylaxis is effective to reduce this risk and in large trials, fondaparinux proved superiority over low molecular weight heparin (LMWH) in this indication with the downside of higher complication rates.• Patients in clinical trials are a selected subpopulation and efficacy and safety results need to be confirmed in large cohorts of unselected patients.WHAT THIS STUDY ADDS• In unselected patients undergoing major orthopaedic surgery, thromboprophylaxis with fondaparinux was equally effective to prevent major venous thromboembolism (VTE), but inferior to prevent distal deep vein thrombosis (DVT) compared with low molecular weight heparin.• The rates of bleeding complications or blood transfusions were similar for patients receiving fondaparinux and LMWH, but use of fondaparinux was associated with significantly lower rates of surgical complications, which contributed to a shorter hospital stay.• Overall, we found much higher rates of symptomatic VTE and bleeding events in our large cohort of unselected patient in daily care compared with results of large phase III trials evaluating anticoagulants in this indication, indicating a selection bias in these prospective trials.AIMS In large randomized trials, thromboprophylaxis with fondaparinux in major orthopaedic surgery (MOS) has been shown to be superior to low molecular weight heparin (LMWH) prophylaxis with comparable safety. However, patients treated under trial conditions are different from unselected patients and efficacy and safety outcomes may be different in unselected patients in daily practice. We performed a retrospective cohort study to compare the efficacy and safety of venous thromboembolism (VTE) prophylaxis with fondaparinux or LMWH in 3896 consecutive patients undergoing major orthopaedic surgery at our centre.METHODS All patients undergoing MOS between January 2006 and December 2009 were retrospectively analyzed using patient charts, hospital admission and discharge database, quality management database, transfusion unit database and VTE event documentation. VTE standard prophylaxis at our institution was LMWH (3000–6000 aXa units once daily) from January 2006 to December 2007 or fondaparinux 2.5 mg from January 2008 to December 2009. In these two large cohorts of unselected consecutive patients, in‐hospital incidences of VTE, surgical complications, severe bleeding and death were evaluated.RESULTS Symptomatic VTE was found in 4.1% of patients in the LMWH group (62/1495 patients; 95% CI 0.032, 0.052) compared with 5.6% of patients receiving fondaparinux (112/1994 patients, 95% CI 0.047, 0.067; P= 0.047). Distal deep vein thrombosis (DVT) was significantly more frequent in the fondaparinux group (3.9%, 95% CI 0.031, 0.048; vs. 2.5%; 95% CI 0.018, 0.034; P= 0.021). No significant differences in the rates of major VTE or death were found. Rates of severe bleeding, transfusion of RBC concentrates, plasma and platelet concentrates were comparable between both treatment groups. However, patients receiving fondaparinux had significantly lower rates of surgical revisions (1.6%, 95% CI 0.011, 0.022 vs. 3.7%, 95% CI 0.028, 0.047; P < 0.001). Multivariate analysis revealed previous VTE (HR 18.2, 95% CI 11.6, 28.5; P < 0.001) and female gender (HR 1.9, 95% CI 1.3, 2.7; P < 0.001), but not fondaparinux prophylaxis (HR1.3, 95% CI 0.9, 1.7; P= 0.184) to be associated with significantly increased VTE risk.DISCUSSION Thromboprophylaxis with fondaparinux is less effective to prevent distal VTE than LMWH in unselected patients undergoing MOS, but is equally effective with regard to rates of major VTE and death. However, differences in efficacy of LMWH or fondaparinux are of little relevance compared with a history of VTE or female gender, which were found to be the main VTE risk factors in MOS. The safety profile of fondaparinux was comparable with LMWH with regard to rates of severe bleeding complications, but patients receiving fondaparinux had significantly less surgical complications requiring surgical revisions. Both our efficacy and safety findings differ from data derived from large phase III trials testing fondaparinux against LMWH in MOS, where overall rates of symptomatic VTE were lower and the safety profile of fondaparinux was different.CONCLUSION We conclude that the strict patient selection and surveillance in phase‐III trials results in lower VTE and bleeding event rates compared with unselected routine patients. Consequently, the efficacy and safety profile of thromboprophylaxis regimens needs to be confirmed in large registries or phase IV trials of unselected patients.

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Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison

Abstract: Drugs that act through specific inhibition of factor Xa, such as fondaparinux, could be more effective than low molecular weight heparins in prevention of venous thromboembolism in patients undergoing hip-replacement surgery.

Cited by 418 publications

References 24 publications

Prevention of Venous Thromboembolism in Surgical Patients

Prevention of Venous Thromboembolism in Surgical Patients

Anti‐PF4/heparin antibody formation postorthopedic surgery thromboprophylaxis: the role of non‐drug risk factors and evidence for a stoichiometry‐based model of immunization

Efficacy and safety of venous thromboembolism prophylaxis with fondaparinux or low molecular weight heparin in a large cohort of consecutive patients undergoing major orthopaedic surgery – findings from the ORTHO‐TEP registry

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