A SYSTEMATIC REVIEW OF THE DETERMINATION OF COSTS AND ECONOMIC BURDEN OF VENOUS THROMBOEMBOLISM: LMWH AS A PHARMAECONOMIC PREVENTIVE THERAPY

Yıl 2020, , 67 - 95, 30.04.2020

Gülsüm Şeyma Koca , Yusuf Çelik

https://doi.org/10.22139/jobs.665042

Öz

Aim: Venous thromboembolism (VTE) is a common clinical problem that has both high morbidity and mortality and creates an economic burden for health systems, hospitals and health insurances. The annual incidence of VTE, which is accompanied by deep vein thrombosis (DVT) and Pulmonary Embolism (PTE), is estimated as 1-2 cases per 1000 people. The annual incidence for pulmonary embolism is 23 cases per 100,000 patients. Serious complications such as recurrent thromboembolism, post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH) increase the burden of managing VTE. Low Molecular Weight Heparin (LMWH) is generally used as an anticoagulant therapy in the treatment and prevention of VTE. The aim of this study was to determine the treatment costs of Venous Thromboembolism, Pulmonary Embolism, Deep Vein Thrombosis and to determine the economic burden that Low Molecular Weight Heparin, a preventive anticoagulant treatment, brings to a health insurance or hospital.
Yöntem: In the study, systematic review analysis was used in the selection of the articles reported for the determination of economic burden. All studies addressing the direct/indirect costs of VTE, DVT, PE or both according to the inclusion and exclusion criteria and reporting the costs of anticagulant therapy used to prevent these complications were discussed. Selected studies are prospective observational studies or retrospective studies, systematic review studies. One of the steps followed during systematic compilation is database scanning. 1659 articles determined by database scans: 119 articles were determined in WOS, 263 in Scopus, 323 in Pubmed, and 954 in Science Direct. As a result of the extraction of articles with no open access and duplicate articles, a total of 262 articles, 113 articles not related to the research topic and 72 articles that are not suitable for the research purpose, 77 articles were evaluated for suitability. A total of 35 studies were examined as a result of 42 articles excluded according to their full text.
Bulgular: In the studies reported in this study, the average annual cost for VTE has reached a minimum of $503,322, and in case of re-hospitalization, a maximum of $86,744. While the cost of VTE in the USA varies between ($3,000 - $9,500), it is seen to be between $2,215 and $4,430 in Europe. The economic burden of the reported articles was handled from the perspective of the hospital and the health insurance perspective. In researches that report costs from both the hospital perspective and the health insurance perspective, it has been observed that costs vary depending on whether they are repeated during the follow-up period, applied to private hospitals, whether the case is primary or secondary, or re-hospitalization. When the costs of inpatient care are evaluated within the framework of a health plan, the average cost of VTE is high, as is the private insurance, to the payer according to the recurrence status during the follow-up period. In addition, the cost of re-hospitalization in hospitalized patients was $32,860, those who did not re-hospitalize were $32,178, in the case of outpatient hospitalization, it was determined to be $22,693, and in the absence of re-hospitalization, it was found to be $22,299. The drug cost of VTE has reached $4,142 in patients who have reoccupied. The annual average costs for PE ranged from a minimum of $3,758 to a maximum of $23,050, and the cost varied between $13,018 and $16,644 depending on whether the event was recurrent admission or whether the event was primary diagnosis or secondary diagnosis. The average annual costs for DVT ($3,740.48-$26,292), and the total costs cause a minimum of $1,095 to $10,758, and in the case of PE accompanying DVT, total annual costs ($12,200-$30,404). The purchase cost of DMAH was found to be on average ($127-$211.7) in calculations made over a 7-day dose.
Conclusion: The costs for the treatment of VTE have increased significantly, and hospitalization times in the USA, European countries and Canada have been prolonged. Therefore, it is difficult to make direct comparisons. In addition, there are very few studies in countries other than the USA and small samples and different methodologies of the studies are making this difficult to measure. All this constitutes the limitation of this research. VTE treatment, prevention and difficulties for determining the incidence is seen in Turkey. In Turkey, VTE, DVT, PE and DVT / PE related difficulties in the national incidence of the lack of measurement of venous thromboembolism prophylaxis and diagnosis, examination of the patient only the hospitalized, only the examination of elderly patients, frequent autopsy cases so as to be included in the incidence figures do not get, or autopsy. Various causes cause problems in determining the actual incidence measurements. The scarcity of studies in this area forms the basis of this study. Differences in the clinical guidelines and treatment schemes of countries cause difficulties in calculating costs. However, exposing the costs of complications such as VTE, DVT, PE, which are a very specific issue, is extremely important for the determination of the economic burden on health systems, hospitals and health insurances. The results obtained from this research are important in terms of comparing VTE attacks and current antiguacogulant treatment options applied for the prevention of recurrent VTE, and will provide a significant benefit in estimating the impact of hospitals and health insurance budgets. Due to the lack of future research at the national level to the incidence and prevalence research VT, evaluating the planning of research on a national level in determining the true incidence of VTE and the extremely high efficiency of the cost of drugs used in the treatment of this complication in Turkey, patients of these complications, health insurance, brought the health system Various researches are proposed to determine and alleviate the economic burden.

Anahtar Kelimeler

Venous Thromboembolism, Pulmonary Embolism, Deep Vein Thrombosis, Low Molecular Weight Heparin, Treatment Costs, Systematic Review

VENÖZ TROMBOEMBOLİZMİN MALİYETLERİ VE EKONOMİK YÜKÜNÜN BELİRLENMESİNE İLİŞKİN SİSTEMATİK BİR DERLEME: FARMAEKONOMİK ÖNLEYİCİ BİR TEDAVİ OLARAK DMAH

Öz

Amaç: Bu araştırmada; Venöz Thromboembolizm, Pulmoner Embolizm, Derin Ven Thrombozunun tedavi maliyetlerinin belirlenmesi ve önleyici antikoagülan bir tedavi olan Düşük Molekül Ağırlıklı Heparin bir sağlık sigortasına veya hastaneye getirdiği ekonomik yükün tespit edilmesi amaçlanmıştır.
Yöntem: Araştırmada ekonomik yükün tespiti için raporlanan makalelerin seçiminde sistematik derleme analizinden yararlanılmıştır. Dahil etme ve dışlama kriterlerine göre VTE, DVT, PE veya her ikisinin tedavisindeki doğrudan/dolaylı maliyetlerini ele alan ve bu komplikasyonların önlenmesinde kullanılan antikagülan tedavi maliyetlerini raporlayan tüm çalışmalar ele alınmıştır. Seçilen araştırmalar prospektif gözlemsel araştırmalar veya retrospektif araştırmalar, sistematik derleme araştırmalarıdır. Buna göre, toplam 35 araştırma incelenmiştir.
Bulgular: Araştırmada, VTE için yıllık ortalama maliyet; minimum 503,322$, yeniden yatış olması durumunda maksimum 86.744$’lara kadar ulaşmıştır. ABD’de VTE maliyetleri (3000$-9500$) arasında bir değişim göstermekte iken, Avrupa’da (2.215$-4.030$) arasında olduğu görülmüştür. PE için yıllık ortalama maliyetlerin ise minimum 3.758$ ile maksimum 23.050$ arasında değiştiği, tekrarlı yatış olması durumunda ya da olayın birincil teşhis mi yoksa ikincil mi teşhis olması durumuna göre 13.018$ ile 16.644$ arasında maliyetin bir değişim gösterdiği görülmüştür. DVT için yıllık ortalama maliyetler (3.740,48$-26.292$) arası, toplam maliyetler ise minimum 1.095$ ile 10.758$ arasında bir maliyete neden olmakta, DVT’e eşlik eden PE olması durumunda ise yıllık toplam maliyetler (12.200$-30.404$) dır. DMAH’ın satın alma maliyeti 7 günlük doz üzerinden yapılan hesaplamalarda ortalama olarak (127$-211,7$) bulgulanmıştır.
Sonuç: Bu araştırmadan elde edilen sonuçlar, VTE atakları ve tekrarlayan VTE'nin önlenmesi için uygulanan mevcut antigüakogülan tedavi seçeneklerinin karşılaştırılması açısından önemli olup, hastanelere ve sağlık sigortalarının bütçesine etkisinin tahmininde önemli bir fayda sağlayacaktır.

Anahtar Kelimeler

Venöz Thromboembolizm, Pulmoner Embolizm, Derin Ven Thrombozu, Düşük Molekül Ağırlıklı Heparin, Tedavi Maliyetleri, Sistematik Derleme

Kaynakça

• Aboagye, J. K., Hayanga, J. W., Lau, B. D., Bush, E. L., Shaffer, D. L., Hobson, D. B., ... ve D’Cunha, J. (2018). Venous Thromboembolism in Patients Hospitalized for Lung Transplantation, The Annals of Thoracic Surgery, 105(4): 1071-1076.
• Algattas, H., Damania, D., DeAndrea-Lazarus, I., Kimmell, K. T., Marko, N. F., Walter, K. A., ... ve Jahromi, B. S. (2017). Systematic Review of Safety and Cost-Effectiveness of Venous Thromboembolism Prophylaxis Strategies in Patients Undergoing Craniotomy for Brain Tumor, Neurosurgery, 82(2): 142-154.
• Annemans, L., Robays, H., Bruart, J., ve Verstraeten, P. (2002). Variation in Medical Resource Utilisation in the Management of Pulmonary Embolism in Belgium, Acta Clinica Belgica, 57(1): 11-18.
• Arseven O, Öngen G, Müsellim B. Pulmoner Tromboembolizm. Metintaş M, Editor. Türkiye'de Temel Akciğer Sağlığı Sorunları ve Çözüm Önerileri, Türk Toraks Derneği Beyaz Kitap, l. baskı. Ankara: 2010. 11-18.
• Aujesky, D., Smith, K. J., Cornuz, J., ve Roberts, M. S. (2005). Cost-effectiveness of Low-Molecular-Weight Heparin for Treatment of Pulmonary Embolism, Chest, 128(3): 1601-1610.
• Bain, E., Wilson, A., Tooher, R., Gates, S., Davis, L. J., ve Middleton, P. (2014). Prophylaxis for Venous Thromboembolic Disease in Pregnancy and the Early Postnatal Period, Cochrane Database Syst Rev, 2(2).
• Bamber, L., Muston, D., McLeod, E., Guillermin, A., Lowin, J., ve Patel, R. (2015). Cost-effectiveness Analysis of Treatment of Venous Thromboembolism with Rivaroxaban Compared with Combined Low Molecular Weight Heparin/Vitamin K Antagonist, Thrombosis Journal, 13(1): 20.
• Baser, O. (2011). Prevalence and economic burden of venous thromboembolism after total hip arthroplasty or total knee arthroplasty. Am J Manag Care. 17:6–8.
• Bellone, M., Di Virgilio, R., ve Di Rienzo, P. (2016). Budget Impact Analysis of Apixaban to Treat and Prevent Venous Thromboembolism in Italy, Farmeconomia. Health Economics and Therapeutic Pathways, 17(3).
• Bonafede, M. M., Shorr, A. F., Johnson, B. H., ve Horblyuk, R. (2009). Pcv12 Fondaparınux ıs Economıcally Non-ınferıor to Enoxaparın for the Treatment of Venous Thromboembolısm, Value in Health, 12(3): A142.
• Bullano, M. F., Willey, V., Hauch, O., Wygant, G., Spyropoulos, A. C., ve Hoffman, L. (2005). Longitudinal Evaluation of Health Plan Cost per Venous Thromboembolism or Bleed Event in Patients with a Prior Venous Thromboembolism Event During Hospitalization, Journal of Managed Care Pharmacy, 11(8): 663-673.
• Caprini, J. A., Botteman, M. F., Stephens, J. M., Nadipelli, V., Ewing, M. M., Brandt, S., ... ve Cohen, A. T. (2003). Economic Burden of Long‐Term Complications of Deep Vein Thrombosis After Total Hip Replacement Surgery in the United States, Value in Health, 6(1), 59-74.
• Chan, C. M., & Shorr, A. F. (2010). Venous Thromboembolic Disease in the Intensive Care Unit. In, Seminars in Respiratory and Critical Care Medicine ,31(01):039-046.
• Cohen, A.T, Agnelli, G., Anderson, F.A., Arcelus, J.I., Bergqvist, D., Brecht, J.G., et al. (2007). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost, 98:756–64.
• Collins (2001). Cost of Tresting Deep-Vein Thrombosis, Corresponce: 284-285.
• Creekmore, F. M., Oderda, G. M., Pendleton, R. C., ve Brixner, D. I. (2006). Incidence and Economic Implications of Heparin‐Induced Thrombocytopenia in Medical Patients Receiving Prophylaxis for Venous Thromboembolism, Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 26(10): 1438-1445.
• Dasta, J. F., Pilon, D., Mody, S. H., Lopatto, J., Laliberté, F., Germain, G., ... ve Nutescu, E. A. (2015). Daily Hospitalization Costs in Patients with Deep Vein Thrombosis or Pulmonary Embolism Treated with Anticoagulant Therapy, Thrombosis Research, 135(2): 303-310.
• Deger, C., Ozdemir, O., Bozkurt, K., Demir, M., Ince, B., Kultursay, H., ... & Parali, E. (2013). The cost-of-disease of deep venous thrombosis and its short-and long-term clinical consequences in turkey: An expert panel approach for estimation of costs. Value in Health, 16(3), A282.
• Dobesh, P.P. (2009). Economic burden of venous thromboembolism in hospitalized patients. Pharmacotherapy. 2009;29:943–53.
• Eryiğit, N, (2006), Hemşirelerin Derin Ven Trombozu Konusundaki Bilgi Düzeylerinin Saptanması. Yayınlanmamış Yüksek Lisans Tezi. Afyon: Kocatepe Üniversitesi Sağlık Bilimleri Enstitüsü.
• Fanikos, J., Rao, A., Seger, A. C., Carter, D., Piazza, G., ve Goldhaber, S. Z. (2013). Hospital Costs of Acute Pulmonary Embolism. The American Journal of Medicine, 126(2): 127-132.
• FanikosJ, Stevens L.A, Labreche, M., Piazza G., Catapane, E., Novack, L., Goldhaber, S. Z (2010) Adherence to pharmacological thromboprophylaxis orders in hospitalized patients. Am J Med, 123:536–541.
• Fernandez, M. M., Hogue, S., Preblick, R., ve Kwong, W. J. (2015). Review of the Cost of Venous Thromboembolism. ClinicoEconomics and Outcomes Research: CEOR, 7, 451.
• Geerts, W.H., Bergqvist, D., Pineo, G. F, (2008). Prevention of Venous Throm¬boembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, 8th edn. Chest. 2008, 133:381S–453S.
• Grosse, S. D., Nelson, R. E., Nyarko, K. A., Richardson, L. C., ve Raskob, G. E. (2016). The Economic Burden of Incident Venous Thromboembolism in the United States: A Review of Estimated Attributable Healthcare Costs, Thrombosis Research, 137: 3-10.
• Guanella, R., Ducruet, T., Johri, M. M. M. J., Mıron. M. J., Roussin, A., Desmarais, S., ... ve Lamping, D. L. (2011). Economic Burden and Cost Determinants of Deep Vein Thrombosis During 2 Years Following Diagnosis: A Prospective Evaluation, Journal of Thrombosis and Haemostasis, 9(12): 2397-2405.
• Gussoni, G., Foglia, E., Frasson, S., Casartelli, L., Campanini, M., Bonfanti, M., ... ve Mazzone, A. (2013). Real-World Economic Burden of Venous Thromboembolism and Antithrombotic Prophylaxis in Medical Inpatients, Thrombosis Research, 131(1): 17-23.
• Hawkins, D. W., Langley, P. C., ve Krueger, K. P. (1997). Pharmacoeconomic Model of Enoxaparin Versus Heparin for Prevention of Deep Vein Thrombosis After Total Hip Replacement, American Journal of Health-System Pharmacy, 54(10): 1185-1190.
• Heisen, M., Treur, M. J., Heemstra, H. E., Giesen, E. B., ve Postma, M. J. (2017). Cost-effectiveness Analysis of Rivaroxaban for Treatment and Secondary Prevention of Venous Thromboembolism in the Netherlands, Journal of Medical Economics, 20(8): 813-824.
• Huang, W., Anderson, F. A., Rushton-Smith, S. K., ve Cohen, A. T. (2015). Impact of Thromboprophylaxis Across the US Acute Care Setting. PloS One, 10(3): e0121429.
• Kahler, Z. P., Beam, D. M., ve Kline, J. A. (2015). Cost of Treating Venous Thromboembolism with Heparin and Warfarin Versus Home Treatment with Rivaroxaban, Academic Emergency Medicine, 22(7): 796-802.
• Knight, K. K., Wong, J., Hauch, O., Wygant, G., Aguilar, D., ve Ofman, J. J. (2005). Economic and Utilization Outcomes Associated with Choice of Treatment for Venous Thromboembolism in Hospitalized Patients, Value in Health, 8(3): 191-200.
• Korkmaz, F. D. ve Çullu, M. (2010). Venöz Tromboembolizm ve Hemşirelik Bakımı (2015). Ege Üniversitesi Hemşirelik Fakültesi Dergisi, 31(1): 62-82.
• Kröger, K., Küpper-Nybelen, J., Moerchel, C., Moysidis, T., Kienitz, C., ve Schubert, I. (2012). Prevalence and Economic Burden of Pulmonary Embolism in Germany, Vascular Medicine, 17(5): 303-309.
• Lanitis, T., Leipold, R., Hamilton, M., Rublee, D., Quon, P., Browne, C., ve Cohen, A. T. (2017). Cost-effectiveness of Apixaban Versus Low Molecular Weight Heparin/Vitamin K Antagonist for the Treatment of Venous Thromboembolism and the Prevention of Recurrences, BMC Health Services Research, 17(1): 74.
• Lefebvre, P., Laliberté, F., Nutescu, E. A., Duh, M. S., LaMori, J., Bookhart, B. K., ... ve Kaatz, S. (2012). All-Cause and Potentially Disease-Related Health Care Costs Associated with Venous Thromboembolism in Commercial, Medicare, and Medicaid Beneficiaries. Journal of Managed Care Pharmacy, 18(5), 363-374.
• Lefebvre, P., Laliberté, F., Nutescu, E. A., Duh, M. S., LaMori, J., Bookhart, B. K., ... ve Kaatz, S. (2013). All-Cause and Disease-Related Health Care Costs Associated with Recurrent Venous Thromboembolism. Thrombosis and Haemostasis, 110(12): 1288-1297.
• Lin, J., Lingohr-Smith, M., ve Kwong, W. J. (2014). Incremental Health Care Resource Utilization and Economic Burden of Venous Thromboembolism Recurrence from a US Payer Perspective, Journal of Managed Care Pharmacy, 20(2), 174-186.
• Liu X, Phatak H, Dillon R, Mitchell SA. Epidemiology and Mortality of Venous Thromboembolism Across Patient Populations: A Systematic Literature Review. Presented at the ISPOR 18th Annual International Meeting, New Orleans, LA, USA. May, 2013. Available from: http://www.ispor.org/research_pdfs/43/pdffiles/PCV5.pdf. Accessed September 17, 2018.
• MacDougall, D. A., Feliu, A. L., Boccuzzi, S. J., ve Lin, J. (2006). Economic Burden of Deep-Vein Thrombosis, Pulmonary Embolism, and Post-Thrombotic Syndrome.
• Merli, G., Ferrufino, C. P., Lin, J., Hussein, M., ve Battleman, D. (2010). Hospital-Based Costs Associated with Venous Thromboembolism Prophylaxis Regimens, Journal of Trombosis and Thrombolysis, 29(4): 449-458.
• Merli, G., Ferrufino, C., Lin, J., Hussein, M., ve Battleman, D. (2008). Hospital‐Based Costs Associated with Venous Thromboembolism Treatment Regimens, Journal of Thrombosis and Haemostasis, 6(7): 1077-1086.
• Michael S., Dejan M., Keith R. M., François, L., Dominique L., Patrick L., Jeff S. ve Alok A. K., (2019). Healthcare Resource Utilization and Costs Associated with Venous Thromboembolism in Cancer Patients Treated with Anticoagulants, Journal of Medical Economics, DOI: 10.1080/13696998.2019.1620752.
• Moher, D., A. Liberati, J. Tetzlaff, ve D. G. Altman. (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement, Annals of Internal Medicine, 151 (4): 264. doi:10.7326/0003- 4819-151-4-200908180-00135.
• O’Brien, J. A., ve Caro, J. J. (2002). Direct Medical Cost of Managing Deep Vein Thrombosis According to the Occurrence of Complications. Pharmacoeconomics, 20(9): 603-615.
• Oger, E. (2000). Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d’Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost, 83:657–60.
• Ruppert, A., Steinle, T., ve Lees, M. (2011). Economic Burden of Venous Thromboembolism: A Systematic Review. Journal of Medical Economics, 14(1): 65-74.
• Shermock, K. M, Lau, B.D, Haut, E.R, Hobson, D.B, Ganetsky, V.S, Kraus, P.S, Efird,L.E, Lehmann, C. U, Pinto, B.L, Ross, P.A, Streiff, M.B. (2013). Patterns of non-administration of ordered doses of venous thromboembolism prophylaxis: implications for novel intervention strategies. PLoSOne, 8:e66311.
• Spyropoulos, A. C., ve Lin, J. (2007). Direct Medical Costs of Venous Thromboembolism and Subsequent Hospital Readmission Rates: An Administrative Claims Analysis from 30 Managed Care Organizations, Journal of Managed Care Pharmacy, 13(6): 475-486.
• Tilleul, P., LaFuma, A., Colin, X., ve Ozier, Y. (2006). Estimated Annual Costs of Prophylaxis and Treatment of venous Thromboembolic Events Associated with Major Orthopedic Surgery in France, Clinical and Applied Thrombosis/Hemostasis, 12(4): 473-484.
• Tillman, D. J., Charland, S. L., ve Witt, D. M. (2000). Effectiveness and Economic İmpact Associated with a Program for Outpatient Management of Acute Deep Vein Thrombosis in a Group Model Health Maintenance Organization, Archives of İnternal Medicine, 160(19): 2926-2932.
• Ulusal Venöz Tromboembolizm Profilaksi ve Teedavi Kılavuzu 2010. (2010). Diasan Basım Form Matbaacılık.
• White RH. (2003). The Epidemiology of Venous Thromboembolism. Circulation, 107: I4-I8; https://doi.org/10.1161/01.CIR.0000078468.11849.66.