Venous Thromboembolism Prophylaxis In Major
Comparative Effectiveness ReviewNumber 191VenousThromboembolismProphylaxis in MajorOrthopedic Surgery:Systematic ReviewUpdatee
Comparative Effectiveness ReviewNumber 191Venous Thromboembolism Prophylaxis in MajorOrthopedic Surgery: Systematic Review UpdatePrepared for:Agency for Healthcare Research and QualityU.S. Department of Health and Human Services5600 Fishers LaneRockville, MD 20857www.ahrq.govContract No. 290-2015-00002-IPrepared by:Brown Evidence-based Practice CenterProvidence, RIInvestigators:Ethan M. Balk, M.D., M.P.H.Alexandra G. Ellis, M.Sc.Mengyang Di, M.D., Ph.D.Gaelen P. Adam, M.L.I.S.Thomas A. Trikalinos, M.D., Ph.D.AHRQ Publication No. 17-EHC021-EFJune 2017
This report is based on research conducted by the Brown Evidence-based Practice Center (EPC)under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD(Contract No. 290-2015-00002-I). The findings and conclusions in this document are those of theauthors, who are responsible for its contents; the findings and conclusions do not necessarilyrepresent the views of AHRQ. Therefore, no statement in this report should be construed as anofficial position of AHRQ or of the U.S. Department of Health and Human Services.None of the investigators have any affiliations or financial involvement that conflicts with thematerial presented in this report.The information in this report is intended to help health care decisionmakers—patients andclinicians, health system leaders, and policymakers, among others—make well-informeddecisions and thereby improve the quality of health care services. This report is not intended tobe a substitute for the application of clinical judgment. Anyone who makes decisions concerningthe provision of clinical care should consider this report in the same way as any medicalreference and in conjunction with all other pertinent information, i.e., in the context of availableresources and circumstances presented by individual patients.This report is made available to the public under the terms of a licensing agreement between theauthor and the Agency for Healthcare Research and Quality. This report may be used andreprinted without permission except those copyrighted materials that are clearly noted in thereport. Further reproduction of those copyrighted materials is prohibited without the expresspermission of copyright holders.AHRQ or U.S. Department of Health and Human Services endorsement of any derivativeproducts that may be developed from this report, such as clinical practice guidelines, otherquality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.This report may periodically be assessed for the currency of conclusions. If an assessment isdone, the resulting surveillance report describing the methodology and findings will be found onthe Effective Health Care Program Web site at www.effectivehealthcare.ahrq.gov. Search on thetitle of the report.Persons using assistive technology may not be able to fully access information in this report. Forassistance contact EffectiveHealthCare@ahrq.hhs.gov.Suggested citation: Balk EM, Ellis AG, Di M, Adam GP, Trikalinos TA. VenousThromboembolism Prophylaxis in Major Orthopedic Surgery: Systematic Review Update.Comparative Effectiveness Review No. 191. (Prepared by the Brown Evidence-based PracticeCenter under Contract No. 290-2015-00002-I.) AHRQ Publication No. 17-EHC021-EF.Rockville, MD: Agency for Healthcare Research and Quality; June l.cfm. DOI:https://doi.org/10.23970/AHRQEPCCER191.ii
PrefaceThe Agency for Healthcare Research and Quality (AHRQ), through its Evidence-basedPractice Centers (EPCs), sponsors the development of systematic reviews to assist public- andprivate-sector organizations in their efforts to improve the quality of health care in the UnitedStates. These reviews provide comprehensive, science-based information on common, costlymedical conditions, and new health care technologies and strategies.Systematic reviews are the building blocks underlying evidence-based practice; they focusattention on the strength and limits of evidence from research studies about the effectiveness andsafety of a clinical intervention. In the context of developing recommendations for practice,systematic reviews can help clarify whether assertions about the value of the intervention arebased on strong evidence from clinical studies. For more information about AHRQ EPCsystematic reviews, see .cfm.AHRQ expects that these systematic reviews will be helpful to health plans, providers,purchasers, government programs, and the health care system as a whole. Transparency andstakeholder input are essential to the Effective Health Care Program. Please visit the Web site(www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join anemail list to learn about new program products and opportunities for input.If you have comments on this systematic review, they may be sent by mail to the Task OrderOfficers named below at: Agency for Healthcare Research and Quality, 5600 Fishers Lane,Rockville, MD 20857, or by email to epc@ahrq.hhs.gov.Gopal Khanna, M.B.A.DirectorAgency for Healthcare Research and QualityArlene S. Bierman, M.D., M.S.DirectorCenter for Evidence and Practice ImprovementAgency for Healthcare Research and QualityStephanie Chang, M.D., M.P.H.DirectorEvidence-based Practice Center ProgramCenter for Evidence and Practice ImprovementAgency for Healthcare Research and QualityAysegul Gozu, M.D., M.P.H.Task Order OfficerCenter for Evidence and Practice ImprovementAgency for Healthcare Research and QualityLaura Pincock, Pharm.D., M.P.H.Task Order OfficerCenter for Evidence and Practice ImprovementAgency for Healthcare Research and Qualityiii
AcknowledgmentsThe authors gratefully acknowledge the following individuals for their invaluable assistancein scoping and refining the protocol; understanding the included surgeries, interventions,perioperative management, and outcomes; and interpreting the methodology used by studies:Roy Aaron, M.D.Lifespan Hospital (Brown University)Providence, RIJennifer Racine, M.B.A.Lifespan Hospital (Brown University)Providence, RIAlok Kapoor, M.D., M.S.Memorial Medical Center (University ofMassachusetts)Worcester, MAEric Winer, M.D.Alpert Medical School (Brown University)Providence, RIWe would also like to thank the American Academy of Orthopaedic Surgeons, the AmericanAssociation of Hip and Knee Surgeons, and Medtronic, Inc., who submitted comments on thedraft report through the public comment mechanism.Technical Expert PanelIn conducting a surveillance of the literature since the prior AHRQ report on venousthromboembolism prophylaxis in orthopedic surgery, we consulted several technical, content,and clinical experts. The Technical Experts provided comments on their interpretation of thecurrent state of the evidence and of clinical questions that are currently pertinent to patientmanagement and decisionmaking. Broad expertise and perspectives were sought. Divergent andconflicted opinions are common and perceived as healthy scientific discourse that results in athoughtful, relevant systematic review. Therefore, in the end, study questions, design,methodologic approaches, and/or conclusions do not necessarily represent the views ofindividual technical and content experts.Technical Experts must disclose any financial conflicts of interest greater than 10,000 and anyother relevant business or professional conflicts of interest. Because of their unique clinical orcontent expertise, individuals with potential conflicts may be retained. The TOO and the EPCwork to balance, manage, or mitigate any potential conflicts of interest identified.The list of Technical Experts who provided input to this report follows:Lisa Boggio, M.D.*Rush UniversityChicago, ILCharles Francis, M.D.*University of RochesterRochester, NYClifford Colwell, M.D.Scripps ClinicLa Jolla, CAJoshua J. Jacobs, M.D.*Rush UniversityChicago, ILiv
Jay Lieberman, M.D.University of Southern CaliforniaLos Angeles, CALisa Moores, M.D.Walter Reed National Military MedicalCenterBethesda, MDChristine McDonough, Ph.D.*Boston University School of MedicineBoston, MAC. Michael White, Pharm.D.*University of Connecticut Evidence-basedPractice CenterFarmington, CTMichael Mont, M.D.Sinai HospitalBaltimore, MDKaren Wilk, M.S.*University of Massachusetts School ofMedicineWorcester, MA* Provided input on Draft Report.Peer ReviewersPrior to publication of the final evidence report, we sought input from independent PeerReviewers without financial conflicts of interest. However, the conclusions and synthesis of thescientific literature presented in this report do not necessarily represent the views of individualreviewers.Peer Reviewers must disclose any financial conflicts of interest greater than 10,000 and anyother relevant business or professional conflicts of interest. Because of their unique clinical orcontent expertise, individuals with potential nonfinancial conflicts may be retained. The TOOand the EPC work to balance, manage, or mitigate any potential nonfinancial conflicts of interestidentified.The list of Peer Reviewers follows:James Rickert, M.D.Indiana University School of Medicine,Bedford, INRongwei (Rochelle) Fu, Ph.D.Pacific Northwest Evidence-based PracticeCenterSchool of Public HealthOregon Health & Science UniversityPortland, ORMary Kay Welle, M.S.N.St. Mary’s College Department of NursingScienceNotre Dame, INCourtland Lewis, M.D.Saint Francis Hospital and Medical CenterHartford, CTv
Venous Thromboembolism Prophylaxis in MajorOrthopedic Surgery: Systematic Review UpdateStructured AbstractBackground. Major orthopedic surgeries, such as total knee replacement (TKR), total hipreplacement (THR), and hip fracture (HFx) surgery, carry a high risk for venousthromboembolism (VTE)—deep vein thrombosis (DVT) and pulmonary embolism (PE).Methods. Updating a 2012 review, we compare interventions to prevent VTE after TKR, THR,and HFx surgery. We searched four databases and other sources through June 3, 2016, forrandomized controlled trials (RCTs) and large nonrandomized comparative studies (NRCSs)reporting postoperative VTE, major bleeding, and other adverse events. We conducted pairwisemeta-analyses, Bayesian network meta-analyses, and strength of evidence (SoE) synthesis.Results. Overall, 127 RCTs and 15 NRCSs met criteria. For THR: low molecular weight heparin(LMWH) has lower risk than unfractionated heparin (UFH) of various VTE outcomes (moderateto high SoE) and major bleeding (moderate SoE). LMWH and aspirin have similar risks of totalPE, symptomatic DVT, and major bleeding (low SoE). LMWH has less major bleeding (lowSoE) than direct thrombin inhibitors (DTI), but DTI has lower DVT risks (moderate SoE).LMWH has less major bleeding than vitamin K antagonists (VKA) (high SoE). LMWH andfactor Xa inhibitor (FXaI) comparisons are inconsistent across VTE outcomes, but LMWH hasless major bleeding (high SoE). VKA has lower proximal DVT risk than mechanical devices(high SoE). Longer duration LMWH has lower risk of various VTE outcome risks (low to highSoE). Higher dose LMWH has lower total DVT risk (low SoE) but more major bleeding(moderate SoE). Higher dose FXaI has lower total VTE risk (low SoE). For TKR: LMWH haslower DVT risks than VKA (low to high SoE), but VKA has less major bleeding (low SoE).FXaI has lower risk than LMWH of various VTE outcomes (low to moderate SoE), but LMWHhas less major bleeding (low SoE) and more study-defined serious adverse events (low SoE).Higher dose DTI has lower DVT risk (moderate to high SoE) but more major bleeding (lowSoE). Higher dose FXaI has lower risk of various VTE outcomes (low to moderate SoE). ForHFx surgery: LMWH has lower total DVT risk than FXaI (moderate SoE).Conclusions. VTE prophylaxis after major orthopedic surgery trades off lowered VTE risk withpossible adverse events—in particular, for most interventions, major bleeding. In THR, LMWHhas lower VTE and adverse event risks than UFH, LMWH and aspirin have similar risks of VTEand major bleeding, DTI has lower DVT risk than LMWH but higher major bleeding risk, andhigher dose LMWH has lower DVT risk but higher major bleeding risk than lower dose. In TKR,VKA has higher DVT risk than LMWH but lower major bleeding risk, and higher dose DTI haslower DVT risk but higher major bleeding risk than lower dose. In HFx surgery and for otherintervention comparisons, there is insufficient evidence to assess both benefits and harms, orfindings are inconsistent. Importantly, though, most studies evaluate “total DVT” (an outcome ofunclear clinical significance since it includes asymptomatic and other low-risk DVTs), butrelatively few studies evaluate PE and other clinically important outcomes. This limitation yieldsa high likelihood of selective outcome reporting bias. There is also relatively sparse evidence oninterventions other than LMWH.vi
ContentsExecutive Summary . ES-1Introduction . 1Background . 1Scope . . 2Key Questions . 3Analytic Framework . 4Methods . 6Topic Refinement and Review Protocol . 6Search Strategy . 6Study Eligibility Criteria . 7Populations of Interest . 7Interventions of Interest . 7Comparators of Interest. 7Outcomes of InterestStudy Design . 9Timing . 9Setting . 9Study Selection . 9Data Extraction . 9Risk of Bias Assessment . 10Data Synthesis . 10Narrative and Tabular Synthesis . 10Pairwise Meta-Analysis . 10Network Meta-Analysis . 11Subgroup Analyses and Metaregression . 12Grading the Strength of Evidence . 12Peer Review . 13Results . 14Summary of Studies . 14Randomized Controlled Trials . 15Nonrandomized Comparative Studies . 15Correlation of DVT and PE Across Trials . 15Subgroup Analyses . 16Key Question 1: Comparison of Thromboprophylaxis Intervention Classes . 17Key Question 1: Total Hip Replacement . 18Key Question 1: Total Knee Replacement. 39Key Question 1: Hip Fracture Surgery . 55Key Question 2: Comparison of Within-Class Thromboprophylaxis Interventions . 58Key Question 2: Total Hip Replacement . 58Key Question 2: Total Knee Replacement. 60Key Question 2: Hip Fracture Surgery . 60Key Question 3: Comparison of Dosages and Treatment Durations ofThromboprophylaxis Interventions . 64Key Question 3: Different Doses or Regimens. 64vii
Key Question 3: Different Treatment Durations . 81Key Question 4: Comparison of Single Versus Combination ThromboprophylaxisIntervention Classes . 90Key Question 4: Total Hip Replacement . 90Key Question 4: Total Knee Replacement. 91Key Question 4: Hip Fracture Surgery . 92Key Question 5: Network Meta-Analyses Across Classes of ThromboprophylaxisInterventions . 97Key Question 5: Total Hip Replacement . 97Key Question 5: Total Knee Replacement. 114Key Question 5: Hip Fracture Surgery . 132Key Question 5 (All Surgeries): Total DVT and Major Bleeding Absolute RateEstimates, by Surgery and Class . 145Key Question 6: Comparison of Different Start Times of ThromboprophylaxisInterventions . 146Key Question 6: Total Hip Replacement . 146Key Question 6: Total Knee Replacement. 146Key Question 6: Hip Fracture Surgery . 146Overall Summary and Strength of Evidence . 148Total Hip Replacement . 148Total Knee Replacement . 161Hip Fracture Surgery. 171Discussion . 177Evidence Summary . 178Total Hip Replacement . 178Total Knee Replacement . 178Hip Fracture Surgery. 1780Evidence and Analysis Limitations . 180Future Research Recommendations . 182Conclusions and Clinical Implications . 183References . . 185TablesTable A. Total hip replacement, intervention class versus class:Summary of “sufficient” evidence . ES-15Table B. Total knee replacement, intervention class versus class:Summary of “sufficient” evidence . ES-18Table C. Hip fracture surgery, intervention class versus class:Summary of “sufficient evidence” . ES-19Table D. Total hip replacement, comparison of different doses or treatment durations:Summary of “sufficient” evidence . ES-21Table E. Total knee r eplacement, comparison of different doses or treatment durations:Summary of “sufficient” evidence . ES-22Table 1. Results summary: Total hip replacement, intervention class versus classcomparisons . 35viii
Table 2. Results summary: Total knee replacement, intervention class versus classcomparisons . 52Table 3. Results summary: Hip fracture surgery, intervention class versus class comparisons . 57Table 4. Results summary: Total hip replacement, within-class intervention versusintervention comparisons . 59Table 5. Results summary: Total knee replacement, within-class intervention versusintervention comparisons . 62Table 6. Results summary: Hip fracture surgery, within-class intervention versusintervention comparisons . 63Table 7. Results summary: Total hip replacement, dose comparisons . 67Table 8. Results summary: Total knee replacement, dose comparisons. 75Table 9. Results summary: Total hip replacement, duration comparisons . 83Table 10. Results summary: Total knee replacement, duration comparisons. 88Table 11. Results summary: Hip fracture surgery, duration comparisons . 89Table 12. Results summary: Total hip replacement, single versus combination classcomparisons . 93Table 13. Results summary: Total knee replacement, single versus combination classcomparisons . 95Table 14. Class ranking: Total hip replacement, intervention class comparisons toprevent deep vein thrombosis . 99Table 15. Intervention ranking: Total hip replacement, intervention comparisons toprevent deep vein thrombosis . 104Table 16. Class ranking: Total hip replacement, intervention comparisons to avoidmajor bleeding . 108Table 17. Intervention ranking: Total hip replacement, intervention comparisons to avoidmajor bleeding . 112Table 18. Class ranking: Total knee replacement, intervention class comparisons toprevent deep vein thrombosis . 117Table 19. Intervention ranking: Total knee replacement, intervention class comparisons toprevent deep vein thrombosis . 122Table 20. Class ranking: Total knee replacement, intervention class comparisons to avoidmajor bleeding . 126Table 21. Intervention ranking: Total knee replacement, intervention comparisons to avoidmajor bleeding . 130Table 22. Class ranking: Hip fracture surgery, intervention class comparisons to preventdeep vein thrombosis . 134Table 23. Intervention ranking: Hip fracture surgery, intervention comparisons to preventdeep vein thrombosis . 137Table 24. Class ranking: Hip fracture surgery, intervention comparisons to avoid majorbleeding . 140Table 25. Intervention ranking: Hip fracture surgery, intervention comparisons to avoidmajor bleeding . 143Table 26. Estimated proportion of patients with total deep vein thrombosis after surgery,by intervention class . 145Table 27. Results summary: Total hip replacement, treatment initiation time comparisons . 147Table 28. Evidence profile for total hip replacement surgery . 155ix
Table 29. Evidence profile for total knee replacement surgery . 167Table 30. Evidence profile for hip fracture surgery. 175FiguresFigure 1. Analytic framework for the comparative effectiveness of venousthromboembolism prophylaxis in orthopedic surgery. 5Figure 2. Literature flow . 17Figure 3. Forest plot: Total hip replacement, major bleeding, LMWH versus DTI . 20Figure 4. Forest plot: Total hip replacement, total venothromboembolism, LMWHversus FXaI. 21Figure 5. Forest plot: Total hip replacement, symptomatic venothromboembolism, LMWHversus FXaI. 22Figure 6. Forest plot: Total hip replacement, total deep vein thrombosis, LMWHversus FXaI. 23Figure 7. Forest plot: Total hip replacement, symptomatic deep vein thrombosis, LMWHversus FXaI. 24Figure 8. Forest plot: Total hip replacement, proximal deep vein thrombosis, LMWHversus FXaI. 25Figure 9. Forest plot: Total hip replacement, major bleeding, LMWH versus FXaI . 26Figure 10. Forest plot: Total hip replacement, serious adverse events, LMWH versus FXaI
Comparative Effectiveness Review . Number 191 . Venous Thromboembolism Prophylaxis in Major Orthopedic Surgery: Systematic Review Update . Prepared for: Agency for Healthcare Research and Quality . U.S. Department of Health and Human Services . 5600 Fishers Lane . Rockville, MD 20857 . ww
Clinical Case Studies in Venous Thromboembolism: Using Direct Oral Anticoagulants for Treatment and Secondary Prevention Activity Overview Clinical case studies will be used to illustrate the decision-making process regarding the acute treatment and secondary prevention of venous thromboembolism (VTE) based on recently updated guidelines and
Table 28: VTE prophylaxis in bariatric surgery .47 . 6 . Introduction Venous thromboembolism (VTE), a disease which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE) is a major health-care problem
Administration of pharmacological deep vein thrombosis prophylaxis within the first 72 hours post ABI may be effective for reducing the risk of developing deep vein thrombosis. Enoxaparin is effective for the prevention of Venous Thromboembolism development after elective neurosu
Pediatric venous thromboembolism (VTE) is a life-threatening condition associated with increased . It is increasingly being recognized as a complication of contemporary health care in the pediatric population. 2. Estimated annual incidence among hospitalized pediatric patients is upwards of 60 events per 10,000 admissions. . (PICC). 3.2.3 .
The VICI VENOUS STENT System has been sterilized with ethylene oxide. Contents One (1) VICI VENOUS STENT Delivery System INTENDED USE The VICI VENOUS STENT is intended for the treatment of obstructions and occlusions in the venous vasculature. INDICATIONS FOR USE The VICI VENOUS STENT System is indicated for improving luminal diameter
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12. Ali NS, Nawaz A, Junaid M, Kazi M, Akhtar S. Venous Thromboembolism-Incidence of Deep Venous Thrombosis and Pulmonary Embolism in Patients with Head and Neck Cancer: A Tertiary Care Experience in Pakistan. Int Arch
2 advanced bookkeeping tutor zone 1.1 Link the elements of the accounting system on the left with their function on the right. FINANCIAL DOCUMENTS BOOKS OF PRIME ENTRY DOUBLE-ENTRY SYSTEM OF LEDGERS TRIAL BALANCE FINANCIAL STATEMENTS 1 The accounting system Summaries of accounting information
