Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2018

Open Access 01-12-2018 | Research article

Low molecular weight heparin versus other anti-thrombotic agents for prevention of venous thromboembolic events after total hip or total knee replacement surgery: a systematic review and meta-analysis

Authors: Xin Lu, Jin Lin

Published in: BMC Musculoskeletal Disorders | Issue 1/2018

Login to get access

Abstract

Background

Venous thromboembolism (VTE) is an important complication following total hip replacement (THR) and total knee replacement (TKR) surgeries. Aim of this study was to comprehensively compare the clinical outcomes of low-molecular-weight heparin (LMWH) with other anticoagulants in patients who underwent TKR or THR surgery.

Methods

Medline, Cochrane, EMBASE, and Google Scholar databases were searched for eligible randomized controlled studies (RCTs) published before June 30, 2017. Meta-analyses of odds ratios were performed along with subgroup and sensitivity analyses.

Results

Twenty-one RCTs were included. In comparison with placebo, LMWH treatment was associated with a lower risk of VTE and deep vein thrombosis (DVT) (P values < 0.001) but similar risk of pulmonary embolism (PE) (P = 0.227) in THR subjects. Compared to factor Xa inhibitors, LMWH treatment was associated with higher risk of VTE in TKR subjects (P < 0.001), and higher DVT risk (P < 0.001) but similar risk of PE and major bleeding in both THR and TKR. The risk of either VTE, DVT, PE, or major bleeding was similar between LMWH and direct thrombin inhibitors in both THR and TKR, but major bleeding was lower with LMWH in patients who underwent THR (P = 0.048).

Conclusion

In comparison with factor Xa inhibitors, LMWH may have higher risk of VTE and DVT, whereas compared to direct thrombin inhibitors, LMWH may have lower risk of major bleeding after THR or TKR.
Appendix
Available only for authorised users
Literature
1.
Chapelle C, Rosencher N, Jacques Zufferey P, Mismetti P, Cucherat M, Laporte S. Prevention of venous thromboembolic events with low-molecular-weight heparin in the non-major orthopaedic setting: meta-analysis of randomized controlled trials. Arthroscopy. 2014;30:987–96.CrossRefPubMed
2.
Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, et al. Prevention of VTE in orthopedic surgery patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e278S–325S.CrossRefPubMedPubMedCentral
3.
Thorlund JB, Juhl CB, Roos EM, Lohmander LS. Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms. BMJ. 2015;350:h2747.CrossRefPubMedPubMedCentral
4.
Yeo KS, Lim WS, Lee YH. Deep vein thrombosis in arthroscopic surgery and chemoprophylaxis recommendation in an Asian population. Singap Med J. 2016;57:452–5.CrossRef
5.
6.
Eikelboom JW, Quinlan DJ, O’Donnell M. Major bleeding, mortality, and effi cacy of fondaparinux in venous thromboembolism prevention trials. Circulation. 2009;120:2006–11.CrossRefPubMed
7.
Adam SS, McDuffie JR, Lachiewicz PF, Ortel TL, Williams JW Jr. Comparative effectiveness of new oral anticoagulants and standard thromboprophylaxis in patients having total hip or knee replacement: a systematic review. Ann Intern Med. 2013;159:275–84.CrossRefPubMed
8.
Kwong LM. Therapeutic potential of rivaroxaban in the prevention of venous thromboembolism following hip and knee replacement surgery: a review of clinical trial data. Vasc Health Risk Manag. 2011;7:461–6.CrossRefPubMedPubMedCentral
9.
Hirsh J, Levine MN. Low molecular weight heparin: laboratory properties and clinical evaluation. A review Eur J Surg Suppl. 1994:9–22.
10.
Heit JA, Colwell CW, Francis CW, Ginsberg JS, Berkowitz SD, Whipple J, et al. Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: a phase 2 dose-finding study. Arch Intern Med. 2001;161:2215–21.CrossRefPubMed
11.
Wilke T, Muller S. Nonadherence in outpatient thromboprophylaxis after major orthopedic surgery: a systematic review. Expert Rev Pharmacoecon Outcomes Res. 2010;10:691–700.CrossRefPubMed
12.
13.
Sun Y, Chen D, Xu Z, Shi D, Dai J, Qin J, et al. Deep venous thrombosis after knee arthroscopy: a systematic review and meta-analysis. Arthroscopy. 2014;30:406–12.CrossRefPubMed
14.
Huisman MV, Quinlan DJ, Dahl OE, Schulman S. Enoxaparin versus dabigatran or rivaroxaban for thromboprophylaxis after hip or knee arthroplasty: results of separate pooled analyses of phase III multicenter randomized trials. Circ Cardiovasc Qual Outcomes. 2010;3:652–60.CrossRefPubMed
15.
Hayden JA, van der Windt DA, Cartwright JL, Cote P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158:280–6.CrossRefPubMed
16.
Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.CrossRefPubMedPubMedCentral
17.
Hardy RJ, Thompson SG. Detecting and describing heterogeneity in meta-analysis. Stat Med. 1998;17:841–56.CrossRefPubMed
18.
Takkouche B, Cadarso-Suarez C, Spiegelman D. Evaluation of old and new tests of heterogeneity in epidemiologic meta-analysis. Am J Epidemiol. 1999;150:206–15.CrossRefPubMed
19.
Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002.CrossRefPubMed
20.
Kim SM, Moon YW, Lim SJ, Kim DW, Park YS. Effect of oral factor Xa inhibitor and low-molecular-weight heparin on surgical complications following total hip arthroplasty. Thromb Haemost. 2016;115:600–7.CrossRefPubMed
21.
Eriksson BI, Agnelli G, Gallus AS, Lassen MR, Prins MH, Renfurm RW, et al. Darexaban (YM150) versus enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a randomised phase IIb dose confirmation study (ONYX-3). Thromb Haemost. 2014;111:213–25.CrossRefPubMed
22.
Zou Y, Tian S, Wang Y, Sun K. Administering aspirin, rivaroxaban and low-molecular-weight heparin to prevent deep venous thrombosis after total knee arthroplasty. Blood Coagul Fibrinolysis. 2014;25:660–4.CrossRefPubMed
23.
Eriksson BI, Dahl OE, Huo MH, Kurth AA, Hantel S, Hermansson K, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb Haemost. 2011;105:721–9.CrossRefPubMed
24.
Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010;375:807–15.CrossRefPubMed
25.
Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010;363:2487–98.CrossRefPubMed
26.
Ginsberg JS, Davidson BL, Comp PC, Francis CW, Friedman RJ, Huo MH, et al. Oral thrombin inhibitor dabigatran etexilate vs north American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplast. 2009;24:1–9.CrossRef
27.
Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009;373:1673–80.CrossRefPubMed
28.
Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med. 2009;361:594–604.CrossRefPubMed
29.
Fuji T, Ochi T, Niwa S, Fujita S. Prevention of postoperative venous thromboembolism in Japanese patients undergoing total hip or knee arthroplasty: two randomized, double-blind, placebo-controlled studies with three dosage regimens of enoxaparin. J Orthop Sci. 2008;13:442–51.CrossRefPubMed
30.
Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008;372:31–9.CrossRefPubMed
31.
Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358:2765–75.CrossRefPubMed
32.
Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358:2776–86.CrossRefPubMed
33.
Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost. 2007;5:2178–85.CrossRefPubMed
34.
Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007;370:949–56.CrossRefPubMed
35.
Eriksson BI, Agnelli G, Cohen AT, Dahl OE, Lassen MR, Mouret P, et al. The direct thrombin inhibitor melagatran followed by oral ximelagatran compared with enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement: the EXPRESS study. J Thromb Haemost. 2003;1:2490–6.CrossRefPubMed
36.
Colwell CW Jr, Berkowitz SD, Davidson BL, Lotke PA, Ginsberg JS, Lieberman JR, et al. Comparison of ximelagatran, an oral direct thrombin inhibitor, with enoxaparin for the prevention of venous thromboembolism following total hip replacement. A randomized, double-blind study. J Thromb Haemost. 2003;1:2119–30.CrossRefPubMed
37.
Eriksson BI, Agnelli G, Cohen AT, Dahl OE, Mouret P, Rosencher N, et al. Direct thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement. Thromb Haemost. 2003;89:288–96.CrossRefPubMed
38.
Bergqvist D, Benoni G, Bjorgell O, Fredin H, Hedlundh U, Nicolas S, et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med. 1996;335:696–700.CrossRefPubMed
39.
Planes A, Vochelle N, Darmon JY, Fagola M, Bellaud M, Huet Y. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet. 1996;348:224–8.CrossRefPubMed
40.
Hull RD, Pineo GF, Stein PD, Mah AF, MacIsaac SM, Dahl OE, et al. Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med. 2001;135:858–69.CrossRefPubMed
41.
Tasker A, Harbord R, Bannister GC. Meta-analysis of low molecular weight heparin versus placebo in patients undergoing total hip replacement and post-operative morbidity and mortality since their introduction. Hip Int. 2010;20:64–74.CrossRefPubMed
42.
Ning GZ, Kan SL, Chen LX, Shangguan L, Feng SQ, Zhou Y. Rivaroxaban for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis with trial sequential analysis of randomized controlled trials. Sci Rep. 2016;6:23726.CrossRefPubMedPubMedCentral
43.
Feng W, Wu K, Liu Z, Kong G, Deng Z, Chen S, et al. Oral direct factor Xa inhibitor versus enoxaparin for thromboprophylaxis after hip or knee arthroplasty: systemic review, traditional meta-analysis, dose-response meta-analysis and network meta-analysis. Thromb Res. 2015;136:1133–44.CrossRefPubMed
44.
Gómez-Outes A, Terleira-Fernández AI, Suárez-Gea ML, Vargas-Castrillón E. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons. BMJ. 2012;344
45.
Wolowacz SE, Roskell NS, Plumb JM, Caprini JA, Eriksson BI. Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty. A meta-analysis Thromb Haemost. 2009;101:77–85.CrossRefPubMed
46.
Cohen AT, Hirst C, Sherrill B, Holmes P, Fidan D. Meta-analysis of trials comparing ximelagatran with low molecular weight heparin for prevention of venous thromboembolism after major orthopaedic surgery. Br J Surg. 2005;92:1335–44.CrossRefPubMed
47.
Ma G, Zhang R, Wu X, Wang D, Ying K. Direct factor Xa inhibitors (rivaroxaban and apixaban) versus enoxaparin for the prevention of venous thromboembolism after total knee replacement: A meta-analysis of 6 randomized clinical trials. Thromb Res. 2015;135:816–22.CrossRefPubMed
48.
Neumann I, Rada G, Claro JC, Carrasco-Labra A, Thorlund K, Akl EA, et al. Oral direct Factor Xa inhibitors versus low-molecular-weight heparin to prevent venous thromboembolism in patients undergoing total hip or knee replacement: a systematic review and meta-analysis. Ann Intern Med. 2012;156:710–9.CrossRefPubMed
49.
Nieto JA, Espada NG, Merino RG, González TC. Dabigatran, rivaroxaban and apixaban versus enoxaparin for thomboprophylaxis after total knee or hip arthroplasty: pool-analysis of phase III randomized clinical trials. Thromb Res. 2012;130:183–91.CrossRefPubMed
50.
Li XM, Sun SG, Zhang WD. Apixaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials. Chin Med J. 2012;125:2339–45.PubMed
51.
Raskob GE, Gallus AS, Pineo GF, Chen D, Ramirez LM, Wright RT, et al. Apixaban versus enoxaparin for thromboprophylaxis after hip or knee replacement: pooled analysis of major venous thromboembolism and bleeding in 8464 patients from the ADVANCE-2 and ADVANCE-3 trials. J Bone Joint Surg Br. 2012;94:257–64.CrossRefPubMed
52.
Huang J, Cao Y, Liao C, Wu L, Gao F. Apixaban versus enoxaparin in patients with total knee arthroplasty. A meta-analysis of randomised trials. Thromb Haemost. 2011;105:245–53.CrossRefPubMed
53.
Cao YB, Zhang JD, Shen H, Jiang YY. Rivaroxaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials. Eur J Clin Pharmacol. 2010;66:1099–108.CrossRefPubMed
54.
Melillo SN, Scanlon JV, Exter BP, Steinberg M, Jarvis CI. Rivaroxaban for thromboprophylaxis in patients undergoing major orthopedic surgery. Ann Pharmacother. 2010;44:1061–71.CrossRefPubMed
55.
Eriksson BI, Dahl OE, Rosencher N, Clemens A, Hantel S, Feuring M, et al. Oral dabigatran etexilate versus enoxaparin for venous thromboembolism prevention after total hip arthroplasty: pooled analysis of two phase 3 randomized trials. Thromb J. 2015;13:36.CrossRefPubMedPubMedCentral
56.
Friedman RJ, Dahl OE, Rosencher N, Caprini JA, Kurth AA, Francis CW, et al. Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: a pooled analysis of three trials. Thromb Res. 2010;126:175–82.CrossRefPubMed
57.
Kwok CS, Pradhan S, Yeong JK, Loke YK. Relative effects of two different enoxaparin regimens as comparators against newer oral anticoagulants: meta-analysis and adjusted indirect comparison. Chest. 2013;144:593–600.CrossRefPubMed
Metadata
Title
Low molecular weight heparin versus other anti-thrombotic agents for prevention of venous thromboembolic events after total hip or total knee replacement surgery: a systematic review and meta-analysis
Authors
Xin Lu
Jin Lin
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2018
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-018-2215-3

Other articles of this Issue 1/2018

BMC Musculoskeletal Disorders 1/2018 Go to the issue

Research article

Identification of pain categories associated with change in pain in patients receiving placebo: data from two phase 3 randomized clinical trials in symptomatic knee osteoarthritis

Research article

Coronal and sagittal balance in Lenke 5 AIS patients following posterior fusion: important role of the lowest instrument vertebrae selection

Research article

Difference in whole spinal alignment between supine and standing positions in patients with adult spinal deformity using a new comparison method with slot-scanning three-dimensional X-ray imager and computed tomography through digital reconstructed radiography

Research article

Can anthropometric, body composition, and bone variables be considered risk factors for musculoskeletal injuries in Brazilian military students?

Research article

Efficacy of standardized training on a virtual reality simulator to advance knee and shoulder arthroscopic motor skills

Research article

Treatment of aneurysmal bone cysts using endoscopic curettage