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Ezetimibe enhances and stabilizes anticoagulant effect of warfarin

Abstract

Ezetimibe reduces plasma levels of low-density lipoprotein cholesterol by inhibiting Niemann–Pick C1-like protein 1 (NPC1L1). A recent study demonstrated that NPC1L1 plays an important role in absorption of fat-soluble vitamins including vitamin K. We evaluated whether the add-on treatment of ezetimibe affects anticoagulation in patients taking warfarin. Between October 2007 and March 2015, the administration of ezetimibe was started to a total of 101 outpatients who were already on oral anticoagulation with warfarin. We retrospectively analyzed blood lipid levels, prothrombin time international normalized ratio (PT-INR) and time in therapeutic INR range (TTR). Seventy-one patients (70 %) showed increase in PT-INR after ezetimibe treatment (1.96 ± 0.45 to 2.20 ± 0.61, p < 0.001). It was necessary to reduce the warfarin dose in 9 of 101 patients for clinical indication. There was a significant positive correlation between change in PT-INR and statin usage at baseline (p = 0.03). The mean value of changes in PT-INR of patients with taking statin was significantly larger than that of patients without taking statin (0.34 ± 0.54 vs. 0.06 ± 0.36, p = 0.03). There was an increase in the TTR (52 ± 26 to 61 ± 23 %, p < 0.0001) and a decrease in the frequency to change the dose of warfarin after the ezetimibe treatment [45 times of 735 examination days (6 %) to 20 times of 695 examination days (3 %), p = 0.02]. Our data suggest possible drug interaction between warfarin and ezetimibe. Ezetimibe may increase and stabilize the anticoagulant effect of warfarin, especially in patients taking statins.

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Correspondence to Takehiro Hashikata.

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Conflict of interest

Dr. Junya Ako received speaking honorarium from Eisai, Bayer Pharma, Tanabe Mitsubishi, Daiichi-Sankyo, MSD K.K., Boehringer Ingelheim, Kowa, and Kyowa Hakko Kirin. Dr. Minako Yamaoka-Tojo received speaking honorarium from Bayer Pharma, Tanabe Mitsubishi, Daiichi-Sankyo, MSD K.K. The other authors have nothing to disclose regarding this study.

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Hashikata, T., Yamaoka-Tojo, M., Kakizaki, R. et al. Ezetimibe enhances and stabilizes anticoagulant effect of warfarin. Heart Vessels 32, 47–54 (2017). https://doi.org/10.1007/s00380-016-0832-z

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  • DOI: https://doi.org/10.1007/s00380-016-0832-z

Keywords

  • Niemann–Pick C1-like protein 1
  • Vitamin K
  • Ezetimibe
  • Warfarin
  • Time in therapeutic range