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Effects of fasting on warfarin sensitivity index in patients undergoing cardiovascular surgery

  • Yoshiki Katada
  • Shunsaku Nakagawa
  • Akiko Nishimura
  • Yu-ki Sato
  • Hiromi Taue
  • Katsuyuki Matsumura
  • Kazuhiro Yamazaki
  • Kenji Minakata
  • Ikuko Yano
  • Tomohiro Omura
  • Satoshi Imai
  • Atsushi Yonezawa
  • Yuki Sato
  • Takayuki Nakagawa
  • Kenji Minatoya
  • Kazuo MatsubaraEmail author
Pharmacoepidemiology and Prescription
  • 75 Downloads

Abstract

Purpose

Warfarin shows large inter- and intra-individual variabilities in its pharmacokinetics and pharmacodynamics. Sufficient understanding of factors affecting the response to warfarin is necessary to achieve improved outcomes for warfarin therapy. In this study, we evaluated effects of fasting on the anticoagulant properties of warfarin.

Methods

We conducted a retrospective observational study involving a total of 58 patients, who received cardiovascular surgeries and subsequent warfarin therapy. The effect of dietary intake on the anticoagulant properties with warfarin was assessed by measurement of the international normalized ratio of prothrombin time (PT-INR): the anticoagulant activities of warfarin were expressed as the warfarin sensitivity index (WSI). Additionally, fluctuations in WSI during the study period were obtained as differences between the maximum and minimum WSI.

Results

The maximum PT-INR and WSI values were significantly higher for patients who were fasting for different reasons during the postoperative period than those in the group without reduced dietary intake. The differences between maximum and minimum WSI in the fasting group significantly increased compared with those in the groups with moderate or no reduced dietary intake. Meanwhile, effects of other markers of clinical conditions including the baseline Child-Pugh score and Charlson Comorbidity Index on WSI were not significant.

Conclusions

Our results indicate that postoperative fasting was significantly associated with the anticoagulation activity of warfarin. In patients fasting for different reasons during the postoperative period, closer control of PT-INR values and warfarin adjustments may be required to avoid adverse effects such as bleeding in warfarin treatment.

Keywords

Warfarin Dietary intake International normalized ratio of prothrombin time (PT-INR) Warfarin sensitivity index (WSI) 

Notes

Author contributions

Katada, Shunsaku Nakagawa, and Matsubara supervised all stages of the project and contributed to the study concept and design, data acquisition, and interpretation, and analyzed data and critical revision of the manuscript. Nishimura contributed to study design, performed research, analyzed data, and wrote the manuscript. Yu-ki Sato, Taue, and Matsumura contributed to study design, data acquisition and interpretation, and critical revision of the manuscript. Yamazaki, Minakata, and Minatoya contributed to study concept and design, data acquisition and interpretation, and critical revision of the manuscript. Yano, Omura, Imai, Yonezawa, Yuki Sato, and Takayuki Nakagawa contributed to study design, data acquisition and interpretation, and critical revision of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Ethics Committee of the Kyoto University Graduate School of Medicine and Kyoto University Hospital (E2461).

Supplementary material

228_2018_2592_MOESM1_ESM.pdf (38 kb)
Supplemental figure. A comparison between median WSI during hospital stay and WSI observed at first visit to hospital after discharge. (PDF 38 kb)
228_2018_2592_MOESM2_ESM.doc (33 kb)
ESM 2 (DOC 33 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Yoshiki Katada
    • 1
  • Shunsaku Nakagawa
    • 1
  • Akiko Nishimura
    • 1
  • Yu-ki Sato
    • 1
  • Hiromi Taue
    • 1
  • Katsuyuki Matsumura
    • 1
  • Kazuhiro Yamazaki
    • 2
  • Kenji Minakata
    • 2
  • Ikuko Yano
    • 1
    • 3
  • Tomohiro Omura
    • 1
  • Satoshi Imai
    • 1
  • Atsushi Yonezawa
    • 1
  • Yuki Sato
    • 1
  • Takayuki Nakagawa
    • 1
  • Kenji Minatoya
    • 2
  • Kazuo Matsubara
    • 1
    Email author
  1. 1.Department of Clinical Pharmacology and TherapeuticsKyoto University HospitalKyotoJapan
  2. 2.Department of Cardiovascular Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
  3. 3.Department of PharmacyKobe University HospitalKobeJapan

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