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      Cost-Utility Analysis of Venous Thromboembolism Prophylaxis Strategies for People Undergoing Elective Total Hip and Total Knee Replacement Surgeries in the English National Health Service

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          Abstract

          Background: Major orthopedic surgery, such as elective total hip replacement (eTHR) and elective total knee replacement (eTKR), are associated with a higher risk of venous thromboembolism (VTE) than other surgical procedures. Little is known, however, about the cost-effectiveness of VTE prophylaxis strategies in people undergoing these procedures.

          Aim: The aim of this work was to assess the cost-effectiveness of these strategies from the English National Health Service perspective to inform NICE guideline (NG89) recommendations.

          Materials and Methods: Cost-utility analysis, using decision modeling, was undertaken to compare 15 VTE prophylaxis strategies for eTHR and 12 for eTKR, in addition to “no prophylaxis” strategy. The analysis complied with the NICE Reference Case. Structure and assumptions were agreed with the guideline committee. Incremental net monetary benefit (INMB) was calculated, vs. the model comparator (LMWH+ antiembolism stockings), at a threshold of £20,000/quality-adjusted life-year (QALY) gained. The model was run probabilistically. Deterministic sensitivity analyses (SAs) were undertaken to assess the robustness of the results.

          Results: The most cost-effective strategies were LMWH for 10 days followed by aspirin for 28 days (INMB = £530 [95% CI: -£784 to £1,103], probability of being most cost-effective = 72%) for eTHR, and foot pump (INMB = £353 [95% CI: -£101 to £665]; probability of being most cost-effective = 18%) for eTKR. There was considerable uncertainty regarding the cost-effectiveness ranking in the eTKR analysis. The results were robust to change in all SAs.

          Conclusions: For eTHR, LMWH (standard dose) for 10 days followed by aspirin for 28 days is the most cost-effective VTE prophylaxis strategy. For eTKR, the results are highly uncertain but foot pump appeared to be the most cost-effective strategy, followed closely by aspirin (low dose). Future research should focus on assessing cost-effectiveness of VTE prophylaxis in the eTKR population.

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          Thrombosis: a major contributor to the global disease burden.

          Thrombosis is a common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2010 documented that ischemic heart disease and stroke collectively caused one in four deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. We performed a systematic review of the literature on the global disease burden caused by VTE in low-income, middle-income and high-income countries. Studies from western Europe, North America, Australia and southern Latin America (Argentina) yielded consistent results, with annual incidence rates ranging from 0.75 to 2.69 per 1000 individuals in the population. The incidence increased to between 2 and 7 per 1000 among those aged ≥ 70 years. Although the incidence is lower in individuals of Chinese and Korean ethnicity, their disease burden is not low, because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted life-years (DALYs) lost in low-income and middle-income countries, and the second most common cause in high-income countries, being responsible for more DALYs lost than nosocomial pneumonia, catheter-related bloodstream infections, and adverse drug events. VTE causes a major burden of disease across low-income, middle-income and high-income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems, and to evaluate whether improved utilization of preventive measures will reduce the burden.
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            The epidemiology of venous thromboembolism in the community.

            The incidence of venous thromboembolism exceeds 1 per 1000; over 200,000 new cases occur in the United States annually. Of these, 30% die within 30 days; one-fifth suffer sudden death due to pulmonary embolism. Despite improved prophylaxis, the incidence of venous thromboembolism has been constant since 1980. Independent risk factors for venous thromboembolism include increasing age, male gender, surgery, trauma, hospital or nursing home confinement, malignancy, neurologic disease with extremity paresis, central venous catheter/transvenous pacemaker, prior superficial vein thrombosis, and varicose veins; among women, risk factors include pregnancy, oral contraceptives, and hormone replacement therapy. About 30% of surviving cases develop recurrent venous thromboembolism within ten years. Independent predictors for recurrence include increasing age, obesity, malignant neoplasm, and extremity paresis. About 28% of cases develop venous stasis syndrome within 20 years. To reduce venous thromboembolism incidence, improve survival, and prevent recurrence and complications, patients with these characteristics should receive appropriate prophylaxis.
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              Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial.

              The role of aspirin in thromboprophylaxis after total hip arthroplasty (THA) is controversial.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                27 November 2018
                2018
                : 9
                : 1370
                Affiliations
                [1] 1Clinical Pharmacy Department, Faculty of Pharmacy, Cairo University , Giza, Egypt
                [2] 2Clinical and Pharmaceutical Sciences Department, School of Life and Medical Sciences, University of Hertfordshire , Hatfield, United Kingdom
                [3] 3National Guideline Centre, Royal College of Physicians-London , London, United Kingdom
                [4] 4Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford , Oxford, United Kingdom
                [5] 5Guy's and St Thomas' NHS Foundation Trust , London, United Kingdom
                [6] 6Northern Vascular Unit, Freeman Hospital, Newcastle University and Newcastle Hospitals , Newcastle upon Tyne, United Kingdom
                [7] 7Northumbria Healthcare NHS Foundation Trust , North Shields, United Kingdom
                [8] 8Department of Trauma & Orthopaedic Surgery, Basingstoke & North Hampshire Hospital , Basingstoke, United Kingdom
                [9] 9Barts Health NHS Trust , London, United Kingdom
                [10] 10University Hospitals of Leicester NHS Trust , Leicester, United Kingdom
                Author notes

                Edited by: Dominique J. Dubois, Free University of Brussels, Belgium

                Reviewed by: Brian Godman, Karolinska Institutet (KI), Sweden; Jean-Paul Deslypere, Besins Healthcare, Thailand

                *Correspondence: Dalia M. Dawoud ddawoud@ 123456hotmail.com

                This article was submitted to Pharmaceutical Medicine and Outcomes Research, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2018.01370
                6289021
                30564117
                6462e87c-7c1a-4e83-ad8c-afec53c35ab6
                Copyright © 2018 Dawoud, Wonderling, Glen, Lewis, Griffin, Hunt, Stansby, Reed, Rossiter, Chahal, Sharpin and Barry.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 July 2018
                : 07 November 2018
                Page count
                Figures: 3, Tables: 11, Equations: 2, References: 74, Pages: 27, Words: 17108
                Funding
                Funded by: National Institute for Health and Care Excellence 10.13039/100010377
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                venous thromboembolism (vte) prophylaxis,pharmacoeconomics,cost utility analysis (cua),total knee replacement (tkr),total hip replacement (thr),direct-acting oral anticoagulants,nice guideline

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