Fondaparinux Compared with Enoxaparin for the Prevention of Venous Thromboembolism after Elective Major Knee Surgery

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

doi:10.1056/nejmoa011099

Cited by 579 publications

(393 citation statements)

References 15 publications

Supporting

Mentioning

365

Contrasting

Unclassified

Order By: Relevance

“…Differences in VTE rates were also not explained by different observation periods. Our retrospective evaluation documented symptomatic VTE events until hospital discharge (mean 10.5 days), while phase III trials in this indication evaluated symptomatic VTE events until day 11 [8,10,11].…”

Section: High Rate Of Symptomatic Vte In Unselected Routine Patientsmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Section: High Rate Of Symptomatic Vte In Unselected Routine Patientsmentioning

confidence: 99%

“…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

View full text Add to dashboard Cite

show abstract

“…The most powerful and effective regime for prophylaxis should be used in these patients despite the fact that it may sometimes be associated with a slightly higher bleeding risk. 29 …”

Section: Antiphospholipid Antibody Syndromementioning

confidence: 99%

Laboratory Markers in the Diagnosis of Venous Thromboembolism

et al. 2004

View full text Add to dashboard Cite

Abstract-Selected blood tests may be useful in the diagnosis of venous thromboembolism (VTE), or in the identification of a congenital or acquired defect associated with the development of VTE. Several studies have shown the D-dimer assay to have a high negative predictive value but poor specificity when used in the detection of VTE. Yet in the emergency room setting, the D-dimer test may be useful if a detailed risk factor analysis for each patient is included in the diagnosis. The presence of such genetic thrombophilia markers as factor V Leiden, prothrombin 20210A mutation, and antiphospholipid antibodies significantly increases a patient's risk of a thrombotic event. The relative risk of thrombosis in factor V heterozygotes is at least 3 times higher than in the general population, whereas the increased risk of thrombosis in homozygotes is estimated to be 50-to 80-fold greater than those without the defect. Thromboembolic events are reported in approximately one third of antiphospholipid-positive patients. Other markers such as hyperhomocysteinemia and deficiencies of antithrombin, protein C, or protein S, when combined with the previous mutations, significantly increase a patient's risk of a thrombotic event. We feel that it is important to identify these ultra-high-risk patients to provide adequate counseling about the risk of thrombosis before elective surgical procedures. Often, lifelong anticoagulation may be needed as these patients and family members may need testing before taking birth control pills or hormonal replacement.

show abstract

“…Postoperative hematoma formation is a well-known complication after hip and knee arthroplasty [1,2,8,9] and in one study was associated with superficial and deep infection [8]. Large hematomas that cause persistent drainage are rare after total joint arthroplasty but may require a return to the operating room for evacuation, irrigation, débridement, and wound closure.…”

Section: Introductionmentioning

confidence: 99%

Infection Associated With Hematoma Formation After Shoulder Arthroplasty

Cheung

Sperling

Cofield

2008

Clinical Orthopaedics &Amp; Related Research

129

View full text Add to dashboard Cite

Hematoma formation requiring operative treatment after shoulder arthroplasty may be associated with higher patient morbidity. We therefore determined whether there was an association of hematoma formation requiring operative treatment with deep infection after shoulder arthroplasty. Between 1978 and 2006, we performed 4147 shoulder arthroplasties in 3643 patients. Of these, 12 shoulders (0.3%) underwent reoperation for hematoma formation. The mean time interval from arthroplasty to surgery for the hematoma was 7 days (range, 0.5-31 days). Among nine cases in which cultures were taken, six had positive cultures; the organisms included Propionibacterium acnes in three, Staphylococcus epidermidis in one, Streptococcus species in one, and Staphylococcus epidermidis with Peptostreptococcus in one. The minimum followup was 12 months (mean, 68 months; range, 12 to 294 months

show abstract

Fondaparinux Compared with Enoxaparin for the Prevention of Venous Thromboembolism after Elective Major Knee Surgery

Abstract: In patients undergoing elective major knee surgery, postoperative treatment with 2.5 mg of fondaparinux once daily was significantly more effective in preventing deep-vein thrombosis than 30 mg of enoxaparin twice daily.

Cited by 579 publications

References 15 publications

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

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

Laboratory Markers in the Diagnosis of Venous Thromboembolism

Infection Associated With Hematoma Formation After Shoulder Arthroplasty

Contact Info

Product

Resources

About