International Journal of Clinical Pharmacy

, Volume 41, Issue 2, pp 546–554 | Cite as

Hospitalization period and direct medical cost in patients using warfarin or novel oral anti‐coagulants after a cerebral embolism

  • Tomohide AkaseEmail author
  • Takanori Tsuchiya
  • Masami Morita
Research Article


Background Warfarin has been used in Japan for a long time in patients after cerebral embolism to prevent recurrence. Recently, several novel oral anti-coagulants (NOACs) have been approved for use and are gradually replacing warfarin. However, it remains unclear whether warfarin and other NOACs differ from each other with respect to drug costs and length of stay (LOS) during treatment in Japan. Objective To assess differences in LOS and direct medical cost between patients after cerebral embolism treated with warfarin and those treated with NOACs. Setting Thirteen acute care hospitals in Japan. Method For hospitalized patients with cerebral embolisms who were treated with NOACs and/or warfarin between April 2012 and March 2014, we assessed LOS for patients with warfarin and NOAC using log-rank test, and stratified proportional hazard regression. Also, we assess direct medical cost using paired-t test. Main Outcome measure LOS and medical cost after first treatment with warfarin and NOAC. Results The median LOS for NOACs-treated patients was 12.5 days and that for warfarin treated patients was 19.0 days while the corresponding mean medical costs were USD 7151 ± 6228 [JPY 736,546 ± 641,437] and USD 8950 ± 5891 [JPY 921,830 ± 606,765]. The drug cost for NOACs-treated patients was higher but costs for laboratory-test and hospitalization were lower than those for warfarin-treated patients. Conclusions For NOAC-treated patients, LOS was shorter, and medical cost during hospitalization tended to be lower than those for warfarin-treated patients, whereas NOACs prices were higher than warfarin price.


DOAC Hospitalization period Japan Medical cost NOAC Novel oral anti-coagulants Warfarin 



This research was not supported by any external funding.

Conflicts of interest

Tomohide Akase has no conflicts of interest to declare. Masami Morita (M.M) was an employee at Shionogi & Co., Ltd at the time of performing this research. Takanori Tsuchiya (T.T) is an employee for Pfizer Japan Inc. However, the roles of M.M and T.T in these companies were not related to this research at the time of conducting the research.

Supplementary material

11096_2019_792_MOESM1_ESM.pptx (76 kb)
Supplementary material 1 (PPTX 75 kb)


  1. 1.
    MHLW. Summary of DPC (Diagnosis Procedure Combination) system and its basic concept. In: Ministry of health Labour and Welfare. 2016. Accessed 18 June 2018.
  2. 2.
    Akase T, Tsuchiya T, Kobayashi M. Study on lengths of stay and use of pharmaceutical products on DPC date in a hospital group. J Jpn Assoc Health Care Adm. 2016;9(1):57–63 (in Japanese).Google Scholar
  3. 3.
    Hamada H, Sekimoto M, Imanaka Y. Effects of the per diem prospective payment system with DRG-like grouping system (DPC/PDPS) on resource usage and healthcare quality in Japan. Health Policy. 2012;107(2–3):194–201.CrossRefGoogle Scholar
  4. 4.
    Kondo A, Kawabuchi K. Evaluation of the introduction of a diagnosis procedure combination system for patient outcome and hospitalisation charges for patients with hip fracture or lung cancer in Japan. Health Policy. 2012;107(2–3):184–93.CrossRefGoogle Scholar
  5. 5.
    Murata A, Matsuda S, Kuwabara K, Ichimiya Y, Fujino Y, Kubo T, et al. Equivalent clinical outcomes of bleeding peptic ulcers in teaching and non-teaching hospitals: evidence for standardization of medical care in Japan. Tohoku J Exp Med. 2011;223(1):1–7.CrossRefGoogle Scholar
  6. 6.
    Kagayama K, Ono S. Duration of clinical developments and approval reviews—based on survey results in 2014. Jpn J Clin Pharmacol Ther. 2015;46(Suppl):S261 (in Japanese).Google Scholar
  7. 7.
    PMDA. List of Approved Products. In: New Drug. 2016. of subordinate document. Accessed 18th June 2018.
  8. 8.
    MHLW. Factor analysis of medical expenditure increasing. In: Cabinet Office, Government Of Japan. 2016. Accessed 1 October 2018 (in Japanese).
  9. 9.
    Tanaka K, Takashima S, Yaguchi Y, Dougu N, Nukui T, Konishi H, et al. Changes in clinical practice after the introduction of non-vitamin K antagonist oral anticoagulants (NOAC) for patients with non-valvular atrial fibrillation. Cereb Blood Flow Metab. 2015;26(2):57–62 (in Japanese).CrossRefGoogle Scholar
  10. 10.
    Toyoda K, Arihiro S, Todo K, Yamagami H, Kimura K, Furui E, et al. Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: the SAMURAI-NVAF study. Int J Stroke. 2015;10(6):836–42.CrossRefGoogle Scholar
  11. 11.
    Senoo K, Lau YC, Dzeshka M, Lane D, Okumura K, Lip GY. Efficacy and safety of non-vitamin K antagonist oral anticoagulants vs warfarin in Japanese patients with atrial fibrillation meta-analysis. Circ J. 2015;79(2):339–45.CrossRefGoogle Scholar
  12. 12.
    Ghanny S, Crowther M. Treatment with novel oral anticoagulants: indications, efficacy and risks. Curr Opin Hematol. 2013;20(5):430–6.CrossRefGoogle Scholar
  13. 13.
    Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.CrossRefGoogle Scholar
  14. 14.
    Srvices HICRR. Master list for drug. In: Health Insurance Claims Review & Reimbursement Srvices. 2012. Accessed 18 June 2018.
  15. 15.
    Srvices HICRR. Master list for medical examination-treatment. In: Health Insurance Claims Review & Reimbursement Srvices. 2012. Accessed 18 June 2018.
  16. 16.
    OECD. PPPs and exchange rates. In: OECD.stat. OECD. Accessed 18 June 2018.
  17. 17.
    Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.CrossRefGoogle Scholar
  18. 18.
    D’Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81.CrossRefGoogle Scholar
  19. 19.
    Hoshino T, Okada K. Estimation of causal effect using propensity score methods in clinical medicine, epidemiology, pharmacoepidemiology and public health; A review. J Natl Inst Public Health. 2006;55(3):230–43 (in Japanese).Google Scholar
  20. 20.
    Group JCSJW. Guidelines for pharmacotherapy of atrial fibrillation (JCS 2013). Circ J. 2014;78(8):1997–2021.CrossRefGoogle Scholar
  21. 21.
    Farr AM, Jing Y, Johnston S, Trocio J, Singhal S, Bruno A, et al. Comparison of hospital length of stay between hospitalized non-valvular atrial fibrillation patients treated with either apixaban or warfarin. Hosp Pract. 2015;43(3):172–9.CrossRefGoogle Scholar
  22. 22.
    Laliberte F, Pilon D, Raut MK, Nelson WW, Olson WH, Germain G, et al. Hospital length of stay: is rivaroxaban associated with shorter inpatient stay compared to warfarin among patients with non-valvular atrial fibrillation? Curr Med Res Opin. 2014;30(4):645–53.CrossRefGoogle Scholar
  23. 23.
    Majeed A, Hwang HG, Connolly SJ, Eikelboom JW, Ezekowitz MD, Wallentin L, et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation. 2013;128(21):2325–32.CrossRefGoogle Scholar
  24. 24.
    Kam JK, Chen Z, Liew D, Yan B. Does warfarin-related intracerebral haemorrhage lead to higher costs of management? Clin Neurol Neurosurg. 2014;126:38–42.CrossRefGoogle Scholar
  25. 25.
    McMurry TL, Hu Y, Blackstone EH, Kozower BD. Propensity scores: Methods, considerations, and applications in the Journal of Thoracic and Cardiovascular Surgery. J Thorac Cardiovasc Surg. 2015;150(1):14–9.CrossRefGoogle Scholar
  26. 26.
    Laliberte F, Cloutier M, Crivera C, Nelson WW, Olson WH, Schein J, et al. Effect of rivaroxaban versus warfarin on health care costs among nonvalvular atrial fibrillation patients: observations from rivaroxaban users and matched warfarin users. Adv Ther. 2015;32(3):216–27.CrossRefGoogle Scholar
  27. 27.
    Sterne JA, Bodalia PN, Bryden PA, Davies PA, Lopez-Lopez JA, Okoli GN, et al. Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis. Health Technol Assess. 2017;21(9):1–386.CrossRefGoogle Scholar
  28. 28.
    Hori M, Koretsune Y, Yasaka M, Shimada I, Fukuda T. Health economic analysis of dabigatran etexilate for stroke prevention in patient with nonvalvular atrial fibrillation. Pharma Medica. 2011;29(4):151–64 (in Japanese).Google Scholar
  29. 29.
    Kimura T, Igarashi A, Ikeda S, Nakajima K, Kashimura S, Kunitomi A, et al. A cost-utility analysis for catheter ablation of atrial fibrillation in combination with warfarin and dabigatran based on the CHADS2 score in Japan. J Cardiol. 2017;69(1):89–97.CrossRefGoogle Scholar
  30. 30.
    Okumura K, Kamae I, Hashimoto Y, Koretsune Y, Tanahashi N, Murata T, et al. Estimation of cost saving effect for non-valvular artrial fibrillation patient treated by apixaban. Med Drug J. 2014;50(3):993–1003 (in Japanese).Google Scholar
  31. 31.
    Hori M, Koretsune Y, Yasaka M, Murata T, Fukaya T, Shibahara T. Burden of cardiovascular event for patient with artrial fibrillation: health economic assessment of dabigatran and warfarin. Pharma Medica. 2015;33(2):87–95 (in Japanese).Google Scholar
  32. 32.
    Kansal AR, Sorensen SV, Gani R, Robinson P, Pan F, Plumb JM, et al. Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation. Heart. 2012;98(7):573–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Tomohide Akase
    • 1
    • 2
    Email author
  • Takanori Tsuchiya
    • 2
    • 3
  • Masami Morita
    • 2
    • 3
  1. 1.Graduate School of BusinessJapan University of EconomicsTokyoJapan
  2. 2.Pharmacy Management InstituteTokyoJapan
  3. 3.Office of Pharmaceutical Industry ResearchTokyoJapan

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