Skip to main content

Advertisement

SpringerLink
Log in

Safety of warfarin therapy in chronic hemodialysis patients: a prospective cohort study

  • Original Article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

We conducted a multicenter prospective cohort study to assess the safety of warfarin therapy in Japanese hemodialysis (HD) patients.

Methods

Chronic HD patients on warfarin therapy (warfarin users) were recruited from 111 HD centers in Japan. Two dialysis-vintage-matched warfarin non-users (non-users) were selected from the same HD center as each warfarin user. Clinical data were collected upon registration and every 12 months thereafter for up to 36 months.

Results

The final cohort consisted of 365 warfarin users and 692 non-users and was followed for an average of 27.7 months. The mean age of warfarin users (68.8 ± 10.6 years) was significantly higher than that of non-users (66.9 ± 11.0 years, p < 0.001). The analyses by multivariate Cox proportional-hazard models showed that the age [hazard ratio (HR) = 1.07 for each 1-year increase, 95 % confidence interval (CI) 1.05–1.08, p < 0.001] was significantly associated with the death from any cause, but warfarin use (1.08, CI 0.75–1.57, p = 0.68) was not when being adjusted for sex, diabetes mellitus, antiplatelet use, and atrial fibrillation. The risk of composite events, which included death from any cause, stroke, cardiovascular disease, and peripheral arterial disease, was also associated with age but was not associated with warfarin use.

Conclusion

The results of this study suggested that warfarin use by HD patients might not be harmful in chronic state, while the safety for the initiation of warfarin therapy in HD patients remained to be determined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Foley RN1, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32(Suppl 3):S112–S119.

  2. Nakai S, Iseki K, Itami N, et al. Overview of regular dialysis treatment in Japan (as of 31 December 2009). Ther Apher Dial. 2012;16:11–53.

    Article  PubMed  Google Scholar 

  3. Vázquez E1, Sánchez-Perales C, Borrego F, et al. Influence of atrial fibrillation on the morbido-mortality of patients on hemodialysis. Am Heart J 2000;140:886–890.

  4. Genovesi S1, Vincenti A, Rossi E, et al. Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients. Am J Kidney Dis 2008;51:255–262.

  5. Vazquez E, Sanchez-Perales C, Garcia-Garcia F, et al. Atrial fibrillation in incident dialysis patients. Kidney Int. 2009;76:324–30.

    Article  PubMed  Google Scholar 

  6. Wizemann V1, Tong L, Satayathum S, et al. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int 2010;77:1098–1106.

  7. Fujii H, Kim JI, Yoshiya K, et al. Clinical characteristics and cardiovascular outcomes of hemodialysis patients with atrial fibrillation: a prospective follow-up study. Am J Nephrol. 2011;34:126–34.

    Article  CAS  PubMed  Google Scholar 

  8. Winkelmayer WC, Patrick AR, Liu J, et al. The increasing prevalence of atrial fibrillation among hemodialysis patients. J Am Soc Nephrol. 2011;22:349–57.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zimmerman D, Sood MM, Rigatto C, et al. Systematic review and meta-analysis of incidence, prevalence and outcomes of atrial fibrillation in patients on dialysis. Nephrol Dial Transplant. 2012;27:3816–22.

    Article  CAS  PubMed  Google Scholar 

  10. Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med. 2012;367:625–35.

    Article  CAS  PubMed  Google Scholar 

  11. Mega JL. A new era for anticoagulation in atrial fibrillation. N Engl J Med. 2011;365:1052–4.

    Article  CAS  PubMed  Google Scholar 

  12. You JJ1, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e531S–e575S.

  13. Chan KE, Lazarus JM, Thadhani R, et al. Anticoagulant and antiplatelet usage associates with mortality among hemodialysis patients. J Am Soc Nephrol. 2009;20:872–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chan KE, Lazarus JM, Thadhani R, et al. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol. 2009;20:2223–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Phelan PJ, O’Kelly P, Holian J, et al. Warfarin use in hemodialysis patients: what is the risk? Clin Nephrol. 2011;75:204–11.

    Article  CAS  PubMed  Google Scholar 

  16. Winkelmayer WC, Liu J, Setoguchi S, et al. Effectiveness and safety of warfarin initiation in older hemodialysis patients with incident atrial fibrillation. Clin J Am Soc Nephrol. 2011;6:2662–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shah M, Avgil Tsadok M, Jackevicius CA, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation. 2014;129:1196–203.

    Article  CAS  PubMed  Google Scholar 

  18. Genovesi S, Rossi E, Gallieni M, et al. Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation. Nephrol Dial Transplant. 2015;30:491–8.

    Article  PubMed  Google Scholar 

  19. Hayashi M, Takamatsu I, Kanno Y, et al. A case-control study of calciphylaxis in Japanese end-stage renal disease patients. Nephrol Dial Transplant. 2012;27:1580–4.

    Article  CAS  PubMed  Google Scholar 

  20. JCS Joint Working Group. Guidelines for Pharmacotherapy of Atrial Fibrillation (JCS 2013). Circ J. 2014;78:1997–2021.

    Article  Google Scholar 

  21. Knoll F, Sturm G, Lamina C, et al. Coumarins and survival in incident dialysis patients. Nephrol Dial Transplant. 2012;27:332–3.

    Article  CAS  PubMed  Google Scholar 

  22. Wakasugi M, Kazama JJ, Tokumoto A, et al. Association between warfarin use and incidence of ischemic stroke in Japanese hemodialysis patients with chronic sustained atrial fibrillation: a prospective cohort study. Clin Exp Nephrol. 2014;18:662–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The results presented in this paper have not been published previously in whole or part, except in abstract format, however, parts of this manuscript were presented in abstract form at the 45th Annual Meeting of the American Society of Nephrology, November 2012, in San Diego and the 47th Annual Meeting of the American Society of Nephrology, November 2014, in Philadelphia. This work was funded by “Research on Intractable Diseases of Health and Labour Sciences Research Grants” from the Ministry of Health, Labour and Welfare of Japan.

The Members of the Warfarin Study Group are

Takuro Kanekawa (Aiseikai Tajirigaoka Hospital), Jiro Teraoka (Kandachi Hospital), Kazumi Akiyama (Akiyama Clinic of Nephrology and Urology), Sayako Hoshi (Adachi Iriya Toneri Clinic), Naoki Aoyama (Arisawa General Hospital), Toshihide Suzuki (Iidabashi Internal Medicine), Hideki Ikenaga (Ikenaga Clinic), Kanji Shishido (Sekishinkai Kawasaki Clinic), Tomoyuki Kita (Sakai Rumi Clinic), Yoshihiko Otsubo (Tenjin-kai Shin-Koga Clinic), Akihiro Chikaraishi (Inagi Kidney Clinic), Tomoyuki Nomura (Inabe General Hospital), Norio Ishida (IMS Miyoshi General Hospital), Kenkichi Kato (Kato Clinic), Kenji Watanabe (Iwami Municipal Hospital), Hideko Nakamura (Ushiku aiwa General Hospital), Hiromasa Uno (Uno Clinic Hokkaido Otaru), Himiko Okuda (Ohme Jin Clinic),Yoshio Nomura (Oita Sanai Medical Center), Eijiro Mihara (Taiseikai Ogaki Kita Clinic), Sadayoshi Ikezaki (Otemachi Clinic), Michihiro Ohya (Ohmori Clinic), Manami Sato (Ojiya general Hospital), Yoshinobu Satoh (Onoba Nephro-Urological Clinic), Kozo Kajino (Kajino Clinic), Hirofumi Nakano (Kashima Hospital), Iwao Michibata (Hakuyukai Hakuyu Clinic), Shigeyuki Katayama (Katayama Clinic), Shinichiro Iyoda (Kanayama Clinic, Nagoya Memorial Foundation), Kenichi Mizowaki (Kamiamakusa General Hospital), Akihide Fukumoto (Kamifukuhara Medical Clinic), Yoshiaki Itaya (Medical corporation Keishinkai Kameido Nephrology Clinic), Akihiro Kawamura (Medical corporation Kawamurakai Kubokawa Hospital), Susumu Uda (Kantoh Rosai Hospital), Kenjiro Kitamura (Kitamura Clinic), Hitoshi Tagawa (Kichijoji Asahi Hospital), Kodama Toshihiro (Kinokawa Clinic), Yoshio Kimura (Kimura Internal Medicine), Chikayuki Yamada (Keiyu Clinic Takanawa), Kazuhiko Tsuruya (Graduate School of Medical Sciences, Kyushu University), Toshihiro Dazai (Keihin Hospital), Kenji Yuasa (Kochi Takasu Hospital), Takeyuki Hiramatsu (Konan Kosei Hospital), Yoji Kaneda (Kobe Kyodo Hospital), Youichi Osako (Kobayashi city Hospital), Kuriyama Satoru (Saiseikai Central Hospital), Tsutomu Inoue (Saitama Medical University), Kazuhiro Horikawa (Saitama Honoka Clinic), Yoshiya Ishikura (Saitoh Medical Clinic), Setsuko Kuroda (Sapporo Kyoritsu Gorinbashi Hospital), Terukazu Yokota (Hakuryuko Hospital), Kazue Ueki (Dialysis and Rheumatolgy Center, Toho-Hospital), Shigeru Otsubo (Sangenjaya Hospital), Genei Ihara (Akebono Hospital), Naohiko Katoh (Shinagawa Renal Clinic), Naoki Satou (Shihoro-cho National Health Insurance Hospital), Yuzuru Kuriyama (Tokai Hospital), Yoshikazu Fuse (Kishiwada Municipal Hospital), Masayuki Kosino (Jinken Clinic), Kiyoshi Ozawa (Shinjinkai Yokosuka Clinic), Maki Takahashi (Suda Naika Clinic), Akiko Okazaki (Seikoukai Kitamura Hospital), Kiyoshi Kitamura (Seikoukai Kitamura Hospital), Seizo Murai (Iidabashi Muraiiin), Eimei Shimoike (Takahashi-naika-clinic), Machiko Shinkai (Shinkai Family Clinic), Tatsuo Tsukamoto (Kitano Hospital,The Tazuke Kofukai Medical Research Institute), Chikamori Masaaki (Chikamori Hospital), Junichi Chihara (Chihara Internal Medicine), Nobuyuki Yoshizawa (Chofu Hospital), Haruo Niwa (Toei National Health Insurance Hospital), Keishi Okada (Tohumi Municipal Hospital), Masakazu Otsuka (Tokiwa Clinic), Kenmei Takaichi (Toranomon Hospital Kidney Center), Fumitada Hattori (Nagao Hospital), Masato Tadokoro (Nagasaki Harbor Medical Center Community Hospital), Daisuke Nakayama (Medical corporation Nakayama Clinic), Daijo Inaguma (Ngoya Daini Red Cross Hospital, Division of Nephrology), Masahiro Nishida (Nishida Medical Clinic), Michihiko Nishimura (Koyo Hospital), Chizuru Ishiguro (Bousei Nishishinjuku Shinryoujou), Chika Onoe (Hattori Hospital), Yuko Tanaka (Toyota Clinic), Takayuki Miyagawa (Miai Clinic), Soichi Sakai (Hibiya Ishikawa Clinic), Shiro Koguma (Kojinkai Nagamachi Clinic), Yoshiyuki Yamaoka (Yushikai Chuki Clinic), Noritoshi Kudoh (Kouwa Clinic, Aomori), Keiji Usui (Bunanomori-Hosoya Clinic), Kazuo Kawagoe (Goi Hospital), Shuji Hoshino (Hoshino Clinic), Kazuko Itoh (2nd Akebono Clinic), Hiroshi Kida (Bohsei Akabane Clinic), Yachiyo Iwamoto (Minamiosawa Paore Renal Clinic), Kouichi Yamaai (Morokuma Hospital), Toshiyuki Araki (Yakuendai Hinyokika Zin Clinic), Hiroaki Watanabe (Yasugi municipal Hospital), Hidehiro Tanji (Yoshida General Hospital), Mamoru Yoshizawa (Yoshizawa Iin), Norimasa Yamashita (Yoyogi Station Clinic).

Author information

Authors and Affiliations

  1. Apheresis and Dialysis Center, Keio University School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan

    Matsuhiko Hayashi, Mieko Iwai, Tadashi Yoshida & Yoshihiko Kanno

  2. Center for Clinical Research, Keio University School of Medicine, Tokyo, Japan

    Takayuki Abe & Yuji Sato

  3. Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan

    Takayuki Abe

  4. Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Ayumi Matsui

  5. Division of Nephrology, Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan

    Yoshihiko Kanno

Authors
  1. Matsuhiko Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takayuki Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mieko Iwai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ayumi Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tadashi Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuji Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoshihiko Kanno
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Warfarin Study Group

Corresponding author

Correspondence to Matsuhiko Hayashi.

Ethics declarations

Conflict of interest

MH has received research Grants from Kyowa Hakko Kirin Co., Ltd., Torii Pharmaceutical Co., Ltd., MSD Co., Ltd, Dai-ichi Sankyo Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., LTD. TA, MI, AM, TY, YS, and YK declared that no conflict of interest exist.

Additional information

Members of the Warfarin Study Group are given Acknowledgments

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hayashi, M., Abe, T., Iwai, M. et al. Safety of warfarin therapy in chronic hemodialysis patients: a prospective cohort study. Clin Exp Nephrol 20, 787–794 (2016). https://doi.org/10.1007/s10157-015-1205-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-015-1205-0

Keywords

Search

Navigation