title: Defining time in therapeutic range for busy clinicians: frequency of dose changes is a good surrogate marker to identify patients with suboptimal anticoagulation with warfarin.
abstract: BACKGROUND
  Patients on warfarin with sub-optimal time-in-therapeutic-range (TTR) are more likely to have adverse events. Target-specific oral anticoagulants (TSOACs) are approved and can be used as an alternative to warfarin for a number of indications. Further, the efficacy and safety profiles of the TSOACs compared to warfarin are more favourable when the TTR is ≤65% for certain indications.
  
  
  OBJECTIVE
  We aimed to determine simple, sensitive and specific diagnostic tools to identify TTR ≤ 65% during the initial three months of warfarin therapy.
  
  
  METHODS
  A cross-sectional study including patients newly initiated on warfarin without any interruption for three months was conducted. TTR was calculated using the Rosendaal method. Patients were stratified by TTR (≤ 65% or >65%). Number of INR measurements, dose changes and INR measurements of ≤ 1.7 or ≥ 4.0 were evaluated as potential diagnostic tools to identify TTR ≤ 65%.
  
  
  RESULTS
  670 patients were included. The most common indication for anticoagulation was venous thromboembolism. The mean TTR in the first three months was 68 ± 21% (Range: 10 to 100%). Three or more dose changes identified TTR ≤ 65% and demonstrated a sensitivity and specificity of 90% (95%CI 86 to 93%) and 56% (95%CI 51 to 61%), respectively. Three or more INR measurements of ≤ 1.7 during the initial three months of anticoagulation showed a sensitivity and specificity of 37% (95%CI 32 to 43%) and 98% (95%CI 96 to 99%), respectively.
  
  
  CONCLUSIONS
  Three or more dose changes and three or more INR measurements of ≤ 1.7 could identify patients with a TTR ≤ 65% in the first three months of warfarin therapy.
authors.affiliation: Department of Medicine, The Ottawa Hospital Research Institute at the University of Ottawa, Ontario, Canada.
authors.forename: Abirami
authors.initials: A
authors.lastname: Vijenthira
authors.affiliation: Department of Medicine, The Ottawa Hospital Research Institute at the University of Ottawa, Ontario, Canada; EA3878, Université de Brest, Brest, France.
authors.forename: Gregoire
authors.initials: G
authors.lastname: Le Gal
authors.affiliation: Department of Medicine, The Ottawa Hospital Research Institute at the University of Ottawa, Ontario, Canada.
authors.forename: Lana A
authors.initials: LA
authors.lastname: Castellucci
authors.affiliation: Department of Medicine, The Ottawa Hospital Research Institute at the University of Ottawa, Ontario, Canada; Institut de Recherche de l'Hôpital Montfort, University of Ottawa, Ontario, Canada. Electronic address: mcarrier@toh.on.ca.
authors.forename: Marc
authors.initials: M
authors.lastname: Carrier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects*; D003430:Cross-Sectional Studies; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D014859:Warfarin / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: Acenocoumarol; Venous thrombosis; Warfarin