Pharmacoeconomic analysis of protrombin complex concentrate (Octaplex preparation) use in intracerebral hemorrhage
Keywords:pharmacoeconomics, intracerebral hemorrhage, prothrombin complex concentrate, reversal of anticoagulants, octaplex
Topicality. Anticoagulant therapy (ACT) is the basis for the prevention and treatment of venous thromboembolic complications (VTEU) after myocardial infarction (MI), acute brain disorders, atrial fibrillation (AF). As an ACT, the indirect anticoagulant warfarin is most commonly used but it may cause small and large bleedings. When developing intracerebral hemorrhage (ICH) on the background of warfarin therapy for reverse hemostatic therapy (RHT), it is recommended to use fresh frozen plasma (FFP) or of prothrombin complex concentrates (CPC).
Aim. To evaluate the pharmacoeconomic feasibility of the CPC (Octaplex drug) use comparing to the emergency dose support for warfarin-associated ICH according to Ukrainian health care system.
Materials and methods. Determination of the results of blood coagulant activity restoration in warfarin-associated ICH with different drugs and associated costs have been performed on soil modeling using the “decision tree” method. The model has been developed on the basis of a randomized trial of the use of FFP and CPC Octaplex warfarin-associated ICH. On the basis of modeling, the methods “total disease cost”, “cost minimization”, “cost-effectivenes” were used. The primary efficacy criterion was the proportion of patients in whom the recovery of the INR within three hours after the onset of RHT was successful. As an additional performance criterion, time was used to recover the INR. They took into account the cost of direct medical expenses, the structure of which was determined in accordance with the current Protocol. The cost of medical treatment has been determined according to the MOH registry as of 7.08.2019. The cost of medical services has been taken from the price lists in licensed clinics. A sensitivity analysis of the results has been performed prior to changes in therapy efficacy data and changes in CPC pricing.
Results and discussion. Determination of direct medical expenses in accordance with the Protocol of the ICH showed that when used for the RHT FFP they amount to 154 911,2 UAH, CPC – 172 773,4 UAH. In the overall cost structure of treating a patient with ICH, the cost of RHT is almost one third. The rate of recovery of INR is an important factor that determines the time of stopping of ICR and, in turn, influences the further prognosis of the disease. Reverse CPC therapy compared to FFP allows to increase the rate of INR recovery 37 times. More than 7 times the number of patients with ICH, who manage to normalize the blood clotting index during the critical 3 hours, is increasing. The Coefficient of Cost Effectiveness (CER) for the primary criterion and the additional criterion when using a CPC is lower by 6.7 and 72.7 times, respectively. That is, using a CPC instead of a FFP is economically feasible. Sensitivity analysis confirmed the robustness of the results. By reducing the price of the CPC by 30%, it becomes the dominant medical technology, that is, providing the best clinical outcome at a lower cost.
Conclusions. Pharmacoeconomic analysis with the use of tree modeling by the decision of the RHT results of warfarin-associated intracerebral hemorrhage with alternative drugs of FFP and CPC Octaplex allows to consider the use of CPC Octaplex economically viable medical technology in the current health protection conditions in Ukraine.
Guyatt, G. H., Akl, E. A., Crowther, M., Gutterman, D. D., Schuünemann, H. J. (2012). Executive Summary. Chest, 141 (2), 7S–47S. doi: https://doi.org/10.1378/chest.1412S3.
Derzhavnyi reiestr likarskykh zasobiv Ukrainy. (n. d.). Available at: https://moz.gov.ua/derzhavnij-reestr-likarskih-zasobiv-ukraini.
Rossaint, R., Bouillon, B., Cerny, V., Coats, T. J., Duranteau, J., Fernández-Mondéjar, E., … Spahn, D. R. (2016). The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Critical Care, 20 (1). doi: https://doi.org/10.1186/s13054-016-1265-x.
Eikelboom, J., Merli, G. (2016). Bleeding with Direct Oral Anticoagulants vs Warfarin: Clinical Experience. The American Journal of Medicine, 129 (11), S33–S40. doi: https://doi.org/10.1016/j.amjmed.2016.06.003.
Nakaz MOZU № 275 vid 17.04.2014 r. “Pro zatverdzhennia ta vprovadzhennia medyko-tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry hemorahichnomu insulti”. (2014). ligazakon.ua. Available at: http://search.ligazakon.ua/l_doc2.nsf/link1/MOZ22644.html.
Sarode, R., Milling, T. J., Refaai, M. A., Mangione, A., Schneider, A., Durn, B. L., Goldstein, J. N. (2013). Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasmacontrolled, phase IIIb study. Circulation, 128 (11), 1234–1243. doi: https://doi.org/10.1161/circulationaha.113.002283.
Chai-Adisaksopha, C., Hillis, C., Siegal, D. M., Movilla, R., Heddle, N., Crowther, M., & Iorio, A. (2016). Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal A systematic review and meta-analysis. Thrombosis and Haemostasis, 116 (11), 879–890. doi: https://doi.org/10.1160/th16-04-0266.
NICE guideline. Stroke and transient ischaemic attack in over 16s: diagnosis and initial management, 2008. (2017). Available at: https://www.nice.org.uk/guidance/cg68.
NICE guideline. Blood transfusion. (2015). Available at: https://www.nice.org.uk/guidance/ng24.
Makris, M., Van Veen, J. J., Tait, C. R., Mumford, A. D., Laffan, M. (2012). Guideline on the management of bleeding in patients on antithrombotic agents. British Journal of Haematology, 160 (1), 35–46. doi: https://doi.org/10.1111/bjh.12107.
Kozek-Langenecker, S. A., Ahmed, A. B., Afshari, A., Albaladejo, P., Aldecoa, C., Barauskas, G., … Zacharowski, K. (2017). Management of severe perioperative bleeding. European Journal of Anaesthesiology, 34 (6), 332–395. doi: https://doi.org/10.1097/EJA.0000000000000630.
Steiner, T., Poli, S., Griebe, M., Hüsing, J., Hajda, J. … Veltkamp, R. (2016). Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. Lancet Neurology, 15, 566–573. doi: https://doi.org/10.1016/S1474-4422(16)00110-1.
Hickey, M., Gatien, M., Taljaard, M., Aujnarain, A., Giulivi, A., Perry, J. J. (2013). Outcomes of urgent warfarin reversal with frozen plasma versus prothrombin complex concentrate in the emergency department. Circulation, 128, 360–364. doi: https://doi.org/10.1161/CIRCULATIONAHA.113.001875.
Riess, H. B., Meier-Hellmann, A., Motsch, J., Elias, M., Kursten, F. W., Dempfle, C. E. (2007). Prothrombin complex concentrate (Octaplex) in patients requiring immediate reversal of oral anticoagulation. Thrombosis Research, 121 (1), 9–16. doi: https://doi.org/10.1016/j.thromres.2007.02.009.
Kolbin, A. S., Kurylev, A. A., Proskurin, M. A., Balykina, A. Ye. (2011). Farmakoekonomicheskaia ekspertiza tcelesoobraznosti primeneniia faktorov svertyvaniia krovi II , VII , IX, X v kombinatcii (protrombinovyi kompleks) v sravnenii s primeneniem svezhezamorozhennoi plazmy i rekombinantnogo aktivirovannogo faktora VII u patcientov s krovotecheniem pri prieme oralnykh antikoaguliantov v usloviiakh ekstrennoi pomoshchi. Farmakoekonomika, 4, 51–58.
Guest, J. F., Watson, H. G., Limaye, S. (2010). Modeling the cost-effectiveness of prothrombin complex concentrate compared with fresh frozen plasma in emergency warfarin reversal in the United Kingdom. Clinical Therapeutics, 32 (14), 2478–2493. doi: https://doi.org/10.1016/j.clinthera.2011.01.011.
Kerivna nastanova iz otsinky tekhnolohii okhorony zdorov’ia. (2018). Kyiv: MOZ Ukrainy, 54.
Yakovlieva, L. V. (Ed.). (2009). Farmakoekonomika. Navchalnyi posibnyk dlia studentiv vyshchykh navchalnykh zakladiv. Vinnytsia: Nova knyha, 208.
Ademi, Z., Kim, H., Zomer, E., Reid, C. M, Hollingsworth, B., Liew, D. (2013). Overview of pharmacoeconomic modelling methods. British Journal of Clinical Pharmacology, 75 (4), 944–950. doi: https://doi.org/10.1111/j.1365-2125.2012.04421.x.
Huttner, H. B., Schellinger, P. D., Hartmann, M., Köhrmann, M., Juettler, E., … Steiner, T. (2006). Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates. Stroke, 37 (6), 1465–1470. doi: https://doi.org/10.1161/01.STR.0000221786.81354.d6.
Gulati, D., Dua, D., Torbey, M. T. (2017). Hemostasis in Intracranial Hemorrhage. Frontiers in Neurology, 8, 80. doi: https://doi.org/10.3389/fneur.2017.00080.
Zadeklarovani optovo-vidpuskni tsiny stanom na 15.01.2018 r. (2018). Available at: http://moz.gov.ua/uploads/0/4022-reestr_lz_stanom_na_15_01_2018.pdf.
Klinika “Dobrobut”. (n. d.). Available at: https://www.dobrobut.com/landings/ambulance.
Tsentr ekstrenoi medychnoi dopomohy ta medytsyny katastrof m. Kyiva. Platni posluhy. (n. d.). Available at: http://ssmp.health.kiev.ua/index.php/2015-03-26-12-19-22.
De M. Soeiro, A., César, M. C., Biselli, B., Siqueira, A., de Carvalho, A. T. … Oliveira, M. T. (2017). Superiority of Prothrombin Complex Concentrate versus Frozen Fresh Plasma in Cardiology Patients with Warfarin Intoxication–Observational Study. Open Journal of Emergency Medicine, 5, 75–84. doi: https://doi.org/10.4236/ojem.2017.52007.
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