title: 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.
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan. t_hashikata@med.kitasato-u.ac.jp.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Hashikata
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.|Department of Rehabilitation, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0373, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Yamaoka-Tojo
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Kakizaki
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Nemoto
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Fujiyoshi
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Namba
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kitasato
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kameda
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Shimohama
authors.affiliation: Department of Rehabilitation, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0373, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Tojo
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Ako
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000925:Anticoagulants / Q000627:therapeutic use*; D001777:Blood Coagulation; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000188:drug therapy*; D000069438:Ezetimibe / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D019934:International Normalized Ratio; D007564:Japan; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011517:Prothrombin Time; D012189:Retrospective Studies; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D000925:Anticoagulants; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014859:Warfarin; D000069438:Ezetimibe
keywords: Ezetimibe; Niemann–Pick C1-like protein 1; Time in therapeutic range; Vitamin K; Warfarin