Background:
Pharmacologic thromboprophylaxis reduces the risk for venous thromboembolism after total hip replacement (THR) or total knee replacement (TKR). New oral anticoagulants (NOACs), including direct thrombin inhibitors and factor Xa inhibitors, are emerging options for thromboprophylaxis after these procedures.
Purpose:
To compare the benefits and risks of NOACs versus standard thromboprophylaxis for adults having THR or TKR.
Data Sources:
MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from January 2009 through March 2013.
Study Selection:
English-language systematic reviews.
Data Extraction:
Two independent reviewers abstracted data and rated study quality and strength of evidence.
Data Synthesis:
Six good-quality systematic reviews compared NOACs with low-molecular-weight heparin (LMWH) for thromboprophylaxis after THR or TKR. Risk for symptomatic deep venous thrombosis, but not risk for death or nonfatal pulmonary embolism, was reduced with factor Xa inhibitors compared with LMWH (4 fewer events per 1000 patients). Conversely, the risk for major bleeding increased (2 more events per 1000 patients). Outcomes of dabigatran did not significantly differ from those of LMWH. Indirect evaluation of NOACs by common comparison with LMWH showed nonsignificantly reduced risks for venous thromboembolism with rivaroxaban compared with dabigatran (risk ratio [RR], 0.68 [95% CI, 0.21 to 2.23]) and apixaban (RR, 0.59 [CI, 0.26 to 1.33]) but increased major bleeding. New oral anticoagulants have not been compared with warfarin, aspirin, or unfractionated heparin.
Limitations:
Head-to-head comparisons among NOACs were not available. Efficacy is uncertain in routine clinical practice.
Conclusion:
New oral anticoagulants are effective for thromboprophylaxis after THR and TKR. Their clinical benefits over LMWH are marginal and offset by increased risk for major bleeding.
Primary Funding Source:
U.S. Department of Veterans Affairs.
References
- 1.
Falck-Ytter Y ,Francis CW ,Johanson NA ,Curley C ,Dahl OE ,Schulman S ,et al .American College of Chest Physicians . 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;141:278S-325S. [PMID: 22315265] CrossrefMedlineGoogle Scholar - 2.
Lieberman JR andHsu WK . Prevention of venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg Am. 2005;87:2097-112. [PMID: 16140827] CrossrefMedlineGoogle Scholar - 3. Sobieraj DM, Coleman CI, Tongbram V, Lee S, Colby J, Chen WT, et al. Venous Thromboembolism in Orthopedic Surgery. Comparative Effectiveness Review no. 49. AHRQ Publication no. 12-EHC020-EF. Rockville, MD: Agency for Healthcare Research and Quality; March 2012. Accessed at www.effectivehealthcare.ahrq.gov/reports/final.cfm on 7 November 2012. Google Scholar
- 4.
Mont MA ,Jacobs JJ ,Boggio LN ,Bozic KJ ,Della Valle CJ ,Goodman SB ,et al .AAOS . Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg. 2011;19:768-76. [PMID: 22134209] CrossrefMedlineGoogle Scholar - 5.
Hill J andTreasure T . Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients having surgery: summary of NICE guidance. BMJ. 2007;334:1053-4. [PMID: 17510154] CrossrefMedlineGoogle Scholar - 6.
Friedman RJ ,Gallus A ,Gil-Garay E ,FitzGerald G , andCushner F . Practice patterns in the use of venous thromboembolism prophylaxis after total joint arthroplasty—insights from the Multinational Global Orthopaedic Registry (GLORY). Am J Orthop (Belle Mead NJ). 2010;39:14-21. [PMID: 21290027] MedlineGoogle Scholar - 7.
Molnar RB ,Jenkin DE ,Millar MJ ,Campbell D , andHarris IA . The Australian arthroplasty thromboprophylaxis survey. J Arthroplasty. 2012;27:173-9. [PMID: 21752576] CrossrefMedlineGoogle Scholar - 8.
Ettema HB ,Mulder MC ,Nurmohamed MT ,Büller HR , andVerheyen CC . Dutch orthopedic thromboprophylaxis: a 5-year follow-up survey. Acta Orthop. 2009;80:109-12. [PMID: 19234891] CrossrefMedlineGoogle Scholar - 9.
Hirsh J andLevine MN . Low molecular weight heparin: laboratory properties and clinical evaluation. A review. Eur J Surg Suppl. 1994;:9-22. [PMID: 7519092] MedlineGoogle Scholar - 10.
Wilke T andMüller S . Nonadherence in outpatient thromboprophylaxis after major orthopedic surgery: a systematic review. Expert Rev Pharmacoecon Outcomes Res. 2010;10:691-700. [PMID: 21155702] CrossrefMedlineGoogle Scholar - 11.
Weitz JI . Low-molecular-weight heparins. N Engl J Med. 1997;337:688-98. [PMID: 9278467] CrossrefMedlineGoogle Scholar - 12.
Turpie AG . Pentasaccharide Org31540/SR90107A clinical trials update: lessons for practice. Am Heart J. 2001;142:S9-15. [PMID: 11479485] CrossrefMedlineGoogle Scholar - 13.
Nutescu E . Characteristics of novel anticoagulants and potential economic implications. Am J Manag Care. 2011;17:S27-32. [PMID: 21517653] MedlineGoogle Scholar - 14.
Fareed J ,Thethi I , andHoppensteadt D . Old versus new oral anticoagulants: focus on pharmacology. Annu Rev Pharmacol Toxicol. 2012;52:79-99. [PMID: 21819239] CrossrefMedlineGoogle Scholar - 15.
Montori VM ,Wilczynski NL ,Morgan D , andHaynes RB ;Hedges Team . Optimal search strategies for retrieving systematic reviews from Medline: analytical survey. BMJ. 2005;330:68. [PMID: 15619601] CrossrefMedlineGoogle Scholar - 16.
Shojania KG andBero LA . Taking advantage of the explosion of systematic reviews: an efficient MEDLINE search strategy. Eff Clin Pract. 2001;4:157-62. [PMID: 11525102] MedlineGoogle Scholar - 17.
Gómez-Outes A ,Terleira-Fernández AI ,Suárez-Gea ML , andVargas-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;344:3675. [PMID: 22700784] CrossrefMedlineGoogle Scholar - 18.
Jacobs JJ ,Mont MA ,Bozic KJ ,Della Valle CJ ,Goodman SB ,Lewis CG ,et al . American Academy of Orthopaedic Surgeons clinical practice guideline on: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Bone Joint Surg Am. 2012;94:746-7. [PMID: 22517391] CrossrefMedlineGoogle Scholar - 19.
Loke YK andKwok CS . Dabigatran and rivaroxaban for prevention of venous thromboembolism—systematic review and adjusted indirect comparison. J Clin Pharm Ther. 2011;36:111-24. [PMID: 21198726] CrossrefMedlineGoogle Scholar - 20.
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 LinkGoogle Scholar - 21.
Ringerike T ,Hamidi V ,Hagen G ,Reikvam A , andKlemp M . Thromboprophylactic treatment with rivaroxaban or dabigatran compared with enoxaparin or dalteparin in patients undergoing elective hip- or knee replacement surgery. Norwegian Knowledge Centre for the Health Services report no. 13. Health Technology Assessment. Oslo Norwegian Knowledge Centre for the Health Services 2011. Google Scholar - 22.
Shea BJ ,Grimshaw JM ,Wells GA ,Boers M ,Andersson N ,Hamel C ,et al . Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007;7:10. [PMID: 17302989] CrossrefMedlineGoogle Scholar - 23.
Moher D ,Cook DJ ,Eastwood S ,Olkin I ,Rennie D , andStroup DF . Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet. 1999;354:1896-900. [PMID: 10584742] CrossrefMedlineGoogle Scholar - 24.
Marinopoulos SS ,Dorman T ,Ratanawongsa N ,Wilson LM ,Ashar BH ,Magaziner JL ,et al . Effectiveness of continuing medical education. Evid Rep Technol Assess (Full Rep). 2007;:1-69. [PMID: 17764217] MedlineGoogle Scholar - 25.
Song F ,Loke YK ,Walsh T ,Glenny AM ,Eastwood AJ , andAltman DG . Methodological problems in the use of indirect comparisons for evaluating healthcare interventions: survey of published systematic reviews. BMJ. 2009;338:b1147. [PMID: 19346285] CrossrefMedlineGoogle Scholar - 26.
Mills EJ ,Ioannidis JP ,Thorlund K ,Schünemann HJ ,Puhan MA , andGuyatt GH . How to use an article reporting a multiple treatment comparison meta-analysis. JAMA. 2012;308:1246-53. [PMID: 23011714] CrossrefMedlineGoogle Scholar - 27.
Guyatt GH ,Oxman AD ,Santesso N ,Helfand M ,Vist G ,Kunz R ,et al . GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes. J Clin Epidemiol. 2013;66:158-72. [PMID: 22609141] CrossrefMedlineGoogle Scholar - 28. Agency for Healthcare Research and Quality. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Rockville, MD: Agency for Healthcare Research and Quality. Accessed at www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&mp=1&productID=318 on 1 August 2012. Google Scholar
- 29.
Schünemann HJ ,Schünemann AH ,Oxman AD ,Brozek J ,Glasziou P ,Jaeschke R ,et al .GRADE Working Group . Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336:1106-10. [PMID: 18483053] CrossrefMedlineGoogle Scholar - 30.
Alves C ,Batel-Marques F , andMacedo AF . Apixaban and rivaroxaban safety after hip and knee arthroplasty: a meta-analysis. J Cardiovasc Pharmacol Ther. 2012;17:266-76. [PMID: 22134134] CrossrefMedlineGoogle Scholar - 31.
Adam SS ,McDuffie JR ,Lachiewicz PF ,Ortel TL , andWilliams JW . Comparative Effectiveness of Newer Oral Anticoagulants and Standard Anticoagulant Regimens for Thromboprophylaxis in Patients Undergoing Total Hip or Knee Replacement. Washington, DC Veterans Affairs Evidence-based Synthesis Program 2012. Google Scholar - 32.
Eriksson BI ,Dahl OE ,Büller HR ,Hettiarachchi R ,Rosencher N ,Bravo ML ,et al .BISTRO II Study Group . A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. J Thromb Haemost. 2005;3:103-11. [PMID: 15634273] CrossrefMedlineGoogle Scholar - 33.
Bucher HC ,Guyatt GH ,Griffith LE , andWalter SD . The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol. 1997;50:683-91. [PMID: 9250266] CrossrefMedlineGoogle Scholar - 34.
Li XM ,Sun SG , andZhang WD . Apixaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials. Chin Med J (Engl). 2012;125:2339-45. [PMID: 22882859] MedlineGoogle Scholar - 35.
Kwok CS ,Pradhan S ,Yeong JK , andLoke YK . Relative effects of two different enoxaparin regimens as comparators against newer oral anticoagulants: meta-analysis and adjusted indirect comparison. Chest. 2013;:. [PMID: 23519234] CrossrefMedlineGoogle Scholar
Author, Article, and Disclosure Information
From Duke University Medical Center and Durham Veterans Affairs Medical Center, Durham, North Carolina; and King Abdulaziz University, Jeddah, Saudi Arabia.
Acknowledgment: The authors thank Connie Schardt for help with the literature search and retrieval and Liz Wing for editorial assistance.
Grant Support: By U.S. Department of Veterans Affairs Office of Research and Development Quality Enhancement Research Initiative (VA-ESP Project 09-010).
Disclosures: Dr. McDuffie: Grant (money to institution): U.S. Department of Veterans Affairs Evidence-based Synthesis Program. Dr. Lachiewicz: Grants/grants pending: Zimmer. Other: Cadence; Journal of Arthroplasty; personal fees from Cadence, Allergan, Gerson Lehrman Group, Global Guidepoint Advisors, Innomed. Dr. Ortel: Consultancy: Instrumentation Laboratory, Bayer, Boehringer Ingelheim, CSL Behring; Grants/grants pending: Eisai, Pfizer, GlaxoSmithKline, Daiichi Sankyo. All other authors have no disclosures. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0383.
Corresponding Author: Soheir S. Adam, MD, Duke University Medical Center, Department of Medicine, Box 3939, Durham, NC 27710; e-mail, [email protected].
Current Author Addresses: Dr. Adam: Department of Medicine, Duke University Medical Center, Box 3939, Durham, NC 27710.
Dr. McDuffie: Durham Veterans Affairs Medical Center, 411 West Chapel Hill Street, Suite 600, Durham, NC 27701.
Dr. Lachiewicz: Department of Surgery, Durham Veteran's Affairs Hospital, Fulton Street, Durham, NC 27701.
Dr. Ortel: Department of Medicine, Duke University Medical Center, DUHS Box 3422, Durham, NC 27710.
Dr. Williams: Durham Veterans Affairs Medical Center, 411 West Chapel Hill Street, Suite 500, Durham, NC 27701.
Author Contributions: Conception and design: S.S. Adam, J.R. McDuffie, T.L. Ortel, J.W. Williams Jr.
Analysis and interpretation of the data: S.S. Adam, J.R. McDuffie, P.F. Lachiewicz, T.L. Ortel, J.W. Williams Jr.
Drafting of the article: S.S. Adam, J.R. McDuffie.
Critical revision of the article for important intellectual content: S.S. Adam, J.R. McDuffie, P.F. Lachiewicz, T.L. Ortel, J.W. Williams Jr.
Final approval of the article: S.S. Adam, J.R. McDuffie, P.F. Lachiewicz, T.L. Ortel, J.W. Williams Jr.
Provision of study materials or patients: J.R. McDuffie.
Obtaining of funding: J.W. Williams Jr.
Administrative, technical, or logistic support: J.R. McDuffie.
Collection and assembly of data: S.S. Adam, J.W. Williams Jr.
Submit a Comment
Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
*All comments submitted after October 1, 2021 and selected for publication will be published online only.