Cost-effectiveness of andexanet alfa versus four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-related intracranial hemorrhage in the US

References

• January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons. Circulation. 2019;140(2):e125–e151.
   PubMed Web of Science ®Google Scholar
• Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315–352.
   PubMed Web of Science ®Google Scholar
• Milling TJ Jr, Clark CL, Feronti C, et al. Management of factor Xa inhibitor-associated life-threatening major hemorrhage: a retrospective multi-center analysis. Am J Emerg Med. 2018;36(3):396–402.
   PubMed Web of Science ®Google Scholar
• Deitelzweig S, Neuman WR, Lingohr-Smith M, et al. Incremental economic burden associated with major bleeding among atrial fibrillation patients treated with factor Xa inhibitors. J Med Econ. 2017;20(12):1217–1223.
   PubMed Web of Science ®Google Scholar
• Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799–808.
   PubMed Web of Science ®Google Scholar
• Obonska K, Navarese EP, Lansky A, et al. Low-dose of oral factor Xa inhibitors in patients with a recent acute coronary syndrome: a systematic review and meta-analysis of randomized trials. Atherosclerosis. 2013;229(2):482–488.
   PubMed Web of Science ®Google Scholar
• Investigators E, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499–2510.
   PubMed Web of Science ®Google Scholar
• Milling TJ Jr, Frontera J. Exploring indications for the use of direct oral anticoagulants and the associated risks of major bleeding. Am J Manag Care. 2017;23(4 suppl):S67–S80.
   PubMed Web of Science ®Google Scholar
• Green L, Tan J, Morris JK, et al. A three-year prospective study of the presentation and clinical outcomes of major bleeding episodes associated with oral anticoagulant use in the UK (ORANGE study). Haematologica. 2018;103(4):738–745.
   PubMed Web of Science ®Google Scholar
• Xian Y, Zhang S, Inohara T, et al. Clinical characteristics and outcomes of intracerebral hemorrhage related to factor Xa inhibitors. JAMA Netw Open. 2021;4(2):e2037438.
   PubMed Web of Science ®Google Scholar
• Connolly SJ, Crowther M, Eikelboom JW, et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019;380(14):1326–1335.
   PubMed Web of Science ®Google Scholar
• Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015;373(25):2413–2424.
   PubMed Web of Science ®Google Scholar
• Demchuk AM, Yue P, Zotova E, et al. Hemostatic efficacy and anti-FXa (factor Xa) reversal with andexanet alfa in intracranial hemorrhage: ANNEXA-4 substudy. Stroke. 2021;52(6):2096–2105.
   PubMed Web of Science ®Google Scholar
• ANDEXXA® (coagulation factor Xa [recombinant], inactivated-zhzo). Lyophilized powder for solution for intravenous injection. [package insert]. Boston, MA: Alexion Pharmaceuticals, Inc.; 2021.
   Google Scholar
• Harrison SK, Garrett JS, Kohman KN, et al. Comparison of outcomes in patients with intracranial hemorrhage on factor Xa inhibitors versus vitamin K antagonists treated with 4-factor prothrombin complex concentrate. Proc (Bayl Univ Med Cent). 2018;31(2):153–156.
   PubMedGoogle Scholar
• Tomaselli GF, Mahaffey KW, Cuker A, et al. 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2020;76(5):594–622.
   PubMed Web of Science ®Google Scholar
• Baugh CW, Levine M, Cornutt D, et al. Anticoagulant reversal strategies in the emergency department setting: recommendations of a multidisciplinary expert panel. Ann Emerg Med. 2020;76(4):470–485.
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Ondexxya (andexanet alfa). Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/ondexxya.
   Google Scholar
• Sanders GD, Neumann PJ, Basu A, et al. Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: Second Panel on Cost-Effectiveness in Health and Medicine. JAMA. 2016;316(10):1093–1103.
   PubMed Web of Science ®Google Scholar
• Yaghi S, Dibu J, Achi E, et al. Hematoma expansion in spontaneous intracerebral hemorrhage: predictors and outcome. Int J Neurosci. 2014;124(12):890–893.
   PubMed Web of Science ®Google Scholar
• Huttner HB, Gerner ST, Connolly S, et al. Andexanet alfa versus usual care in patients with DOAC associated intracerebral hemorrhage: a propensity-score based historical comparison of patients from ANNEXA4 and RETRACE II. Int J Stroke. 2020;15(1 suppl):62.
   Web of Science ®Google Scholar
• Brown CS, Scott RA, Sridharan M, et al. Real-world utilization of andexanet alfa. Am J Emerg Med. 2020;38(4):810–814.
   PubMedGoogle Scholar
• Barra ME, Das AS, Hayes BD, et al. Evaluation of andexanet alfa and four-factor prothrombin complex concentrate (4F-PCC) for reversal of rivaroxaban- and apixaban-associated intracranial hemorrhages. J Thromb Haemost. 2020;18(7):1637–1647.
   PubMed Web of Science ®Google Scholar
• Cohen AT, Lewis M, Connor A, et al. 30 day mortality following andexanet alfa in ANNEXA-4 compared with prothrombin complex concentrate (PCC) therapy in the ORANGE study for life-threatening non-vitamin K oral anticoagulant (NOAC) related bleeding. J Am Coll Cardiol. 2020;75(11):2242.
   Google Scholar
• Alexion Pharmaceuticals. Data on file. [unpublished]. 2020.
   Google Scholar
• Gerner ST, Kuramatsu JB, Sembill JA, et al. Characteristics in non–vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Stroke. 2019;50(6):1392–1402.
   PubMed Web of Science ®Google Scholar
• Schulman S, Gross PL, Ritchie B, et al. Prothrombin complex concentrate for major bleeding on factor Xa inhibitors: a prospective cohort study. Thromb Haemost. 2018;118(5):842–851.
   PubMed Web of Science ®Google Scholar
• Majeed A, Agren A, Holmstrom M, et al. Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood. 2017;130(15):1706–1712.
   PubMed Web of Science ®Google Scholar
• Arachchillage DRJ, Alavian S, Griffin J, et al. Efficacy and safety of prothrombin complex concentrate in patients treated with rivaroxaban or apixaban compared to warfarin presenting with major bleeding. Br J Haematol. 2019;184(5):808–816.
   PubMed Web of Science ®Google Scholar
• Khorsand N, Majeed A, Sarode R, et al. Assessment of effectiveness of major bleeding management: proposed definitions for effective hemostasis: communication from the SSC of the ISTH. J Thromb Haemost. 2016;14(1):211–214.
   PubMed Web of Science ®Google Scholar
• Panos NG, Cook AM, John S, et al. Neurocritical Care Society (NCS) Pharmacy Study Group. Factor Xa inhibitor-related intracranial hemorrhage: results from a multicenter, observational cohort receiving prothrombin complex concentrates. Circulation. 2020;141(21):1681–1689.
   PubMed Web of Science ®Google Scholar
• Gerner ST, Kuramatsu JB, Sembill JA, et al. Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Ann Neurol. 2018;83(1):186–196.
   PubMed Web of Science ®Google Scholar
• Huttner HB, Gerner ST, Kuramatsu JB, et al. Haematoma expansion and clinical outcomes in patients with factor-Xa inhibitor–related atraumatic intracerebral haemorrhage treated within the ANNEXA-4 trial versus real-world usual care: a comparative effectiveness study. Stroke. 2022;53(2):532–543.
   PubMedGoogle Scholar
• Jang MU, Kang J, Kim BJ, et al. In-hospital and post-discharge recovery after acute ischemic stroke: a nationwide multicenter stroke registry-base study. J Korean Med Sci. 2019;34(36):e240.
   PubMed Web of Science ®Google Scholar
• Ganesh A, Luengo-Fernandez R, Wharton RM, et al. Time course of evolution of disability and cause-specific mortality after ischemic stroke: implications for trial design. J Am Heart Assoc. 2017;6(6):e005788.
   PubMed Web of Science ®Google Scholar
• IBM Micromedex. Micromedex Red Book. Available from: https://www.micromedexsolutions.com/micromedex2/librarian/PFDefaultActionId/redbook.ModifyRedBookSearch/ssl/true.
   Google Scholar
• Smith MN, Deloney L, Carter C, et al. Safety, efficacy, and cost of four-factor prothrombin complex concentrate (4F-PCC) in patients with factor Xa inhibitor-related bleeding: a retrospective study. J Thromb Thrombolysis. 2019;48(2):250–255.
   PubMed Web of Science ®Google Scholar
• Frontera JA, Lewin JJ 3rd, Rabinstein AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: executive summary. A statement for healthcare professionals from the Neurocritical Care Society and the Society of Critical Care Medicine. Crit Care Med. 2016;44(12):2251–2257.
   PubMed Web of Science ®Google Scholar
• Shander A, Ozawa S, Hofmann A. Activity-based costs of plasma transfusions in medical and surgical inpatients at a US hospital. Vox Sang. 2016;111(1):55–61.
   PubMed Web of Science ®Google Scholar
• Dasta JF, McLaughlin TP, Mody SH, et al. Daily cost of an intensive care unit day: the contribution of mechanical ventilation. Crit Care Med. 2005;33(6):1266–1271.
   PubMed Web of Science ®Google Scholar
• Halpern NA, Goldman DA, Tan KS, et al. Trends in critical care beds and use among population groups and Medicare and Medicaid beneficiaries in the United States: 2000–2010. Crit Care Med. 2016;44(8):1490–1499.
   PubMed Web of Science ®Google Scholar
• Regan JM, Worley E, Shelburne C, et al. Burr hole washout versus craniotomy for chronic subdural hematoma: patient outcome and cost analysis. PLoS One. 2015;10(1):e0115085.
   PubMed Web of Science ®Google Scholar
• Hoffman H, Furst T, Jalal MS, et al. Annual incidences and predictors of 30-day readmissions following spontaneous intracerebral hemorrhage from 2010 to 2014 in the United States: a retrospective nationwide analysis. Heliyon. 2020;6(1):e03109.
   PubMed Web of Science ®Google Scholar
• Buntin MB, Colla CH, Deb P, et al. Medicare spending and outcomes after postacute care for stroke and hip fracture. Med Care. 2010;48(9):776–784.
   PubMed Web of Science ®Google Scholar
• Shireman TI, Wang K, Saver JL, et al. Cost-effectiveness of solitaire stent retriever thrombectomy for acute ischemic stroke: results from the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke). Stroke. 2017;48(2):379–387.
   PubMed Web of Science ®Google Scholar
• Qureshi AI, Chaudhry SA, Sapkota BL, et al. Discharge destination as a surrogate for Modified Rankin Scale defined outcomes at 3- and 12-months poststroke among stroke survivors. Arch Phys Med Rehabil. 2012;93(8):1408–1413.e1.
   PubMed Web of Science ®Google Scholar
• Centers for Medicare & Medicaid Services, HHS Medicare Program. Hospital inpatient prospective payment systems for acute care hospitals and the Long-Term Care Hospital Prospective Payment System and policy changes and fiscal year 2020 rates; quality reporting requirements for specific providers; Medicare and Medicaid promoting interoperability programs requirements for eligible hospitals and critical access hospitals; 2019. Available from: www.federalregister.gov/documents/2019/08/16/2019-16762/medicare-program-hospital-inpatientprospective-payment-systems-for-acute-care-hospitals-and-the%0D.
   Google Scholar
• John Hopkins Medicine. Appendix B: phytonadione (vitamin K) dosing guidelines. Interdisciplinary clinical practice manual, medication drug use, warfarin, management of the adult patient receiving, MDU023; 2009. [cited 2020 March 25]. Available from: https://www.hopkinsmedicine.org/hematology/anticoagulation/provider_information/guideline_pdfs/warfarin%20reversal.pdf.
   Google Scholar
• Tao J, Bukanova EN, Akhtar S. Safety of 4-factor prothrombin complex concentrate (4F-PCC) for emergent reversal of factor Xa inhibitors. J Intensive Care. 2018;6:34.
   PubMed Web of Science ®Google Scholar
• Heidbuchel H, Verhamme P, Alings M, et al. Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J. 2017;38(27):2137–2149.
   PubMed Web of Science ®Google Scholar
• Coleman CI, Dobesh PP, Danese S, et al. Real-world management of oral factor Xa inhibitor-related bleeds with reversal or replacement agents including andexanet alfa and four-factor prothrombin complex concentrate: a multicenter study. Future Cardiol. 2021;17(1):127–135.
   PubMedGoogle Scholar
• Kunz WG, Hunink MG, Dimitriadis K, et al. Cost-effectiveness of endovascular therapy for acute ischemic stroke: a systematic review of the impact of patient age. Radiology. 2018;288(2):518–526.
   PubMed Web of Science ®Google Scholar
• Ali M, MacIsaac R, Quinn TJ, et al. Dependency and health utilities in stroke: data to inform cost-effectiveness analyses. Eur Stroke J. 2017;2(1):70–76.
   PubMed Web of Science ®Google Scholar
• Portola Pharmaceuticals. U.S. Centers for Medicare & Medicaid Services (CMS) grants new technology add-on payment for Portola Pharmaceuticals’ Andexxa; 2018.
   Google Scholar
• Haque M, Gratson M, Woerle J, et al. Beginning to understand the cost-effectiveness of Andexxa. Georgetown Medical Review. 2019;3(1). DOI:10.52504/001c.7777
   Google Scholar
• Frontera JA, Bhatt P, Lalchan R, et al. Cost comparison of andexanet versus prothrombin complex concentrates for direct factor Xa inhibitor reversal after hemorrhage. J Thromb Thrombolysis. 2020;49(1):121–131.
   PubMed Web of Science ®Google Scholar
• Micieli A, Demchuk AM, Wijeysundera HC. Economic evaluation of andexanet versus prothrombin complex concentrate for reversal of factor Xa-associated intracranial hemorrhage. Stroke. 2021;52(4):1390–1397.
   PubMed Web of Science ®Google Scholar