title: The Impact of Inpatient Versus Outpatient Initiation on Early Warfarin Dosing.
abstract: OBJECTIVE
  Dosing algorithms for warfarin incorporate clinical and genetic factors but may not account for the numerous comorbidities affecting patients who start warfarin while hospitalized. We aimed to determine whether these algorithms perform differently when warfarin is initiated for inpatients compared with outpatients.
  
  
  METHODS
  We analyzed a prospective cohort of 1015 participants from the Clarification of Optimal Anticoagulation through Genetics (COAG) trial who were randomized to either pharmacogenetically or clinically guided warfarin dosing algorithms. Clinicians and participants were blinded to dose during the first 28 days. We compared groups, based on location at the time of the first warfarin dose request, in relation to the following outcomes: percentage of time in the therapeutic international normalized ratio (INR) range (PTTR) during the first 4 weeks, time to first therapeutic INR, time to maintenance dose, and the difference between predicted and observed maintenance doses.
  
  
  RESULTS
  A total of 527 participants started warfarin as inpatients and 488 as outpatients. There was no difference in PTTR based on location: 43.2 % for inpatient versus 47.4 % for outpatient initiation [mean adjusted difference -2.2 %; 95 % confidence interval (CI) -5.9 to 1.6]. Similarly, there were no differences in time to first therapeutic INR [hazard ratio (HR) 1.06; 95 % CI 0.91-1.24] or to maintenance dose (HR 0.96; 95 % CI 0.81-1.14). There was no evidence of interaction between study intervention (pharmacogenetically vs. clinically guided therapy) and location of initiation for these main outcomes. The difference between predicted and observed maintenance doses was similar for both locations.
  
  
  CONCLUSIONS
  The warfarin dosing algorithms performed similarly for subjects who initiated warfarin as inpatients and outpatients, regardless of whether dosing was pharmacogenetically or clinically guided.
authors.affiliation: Department of Neurology, University of Pennsylvania Medical Center, 3W Gates Bldg, 3400 Spruce Street, Philadelphia, PA, 19104, USA, kasner@mail.med.upenn.edu.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kasner
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.forename: Benjamin
authors.initials: B
authors.lastname: French
authors.forename: Steven R
authors.initials: SR
authors.lastname: Messe
authors.forename: Richard
authors.initials: R
authors.lastname: Horenstein
authors.forename: Emile R
authors.initials: ER
authors.lastname: Mohler
authors.forename: James A S
authors.initials: JA
authors.lastname: Muldowney
authors.forename: Jonas
authors.initials: J
authors.lastname: Ellenberg
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kimmel
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007297:Inpatients / Q000706:statistics & numerical data*; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010045:Outpatients / Q000706:statistics & numerical data*; D057285:Precision Medicine / Q000379:methods; D013923:Thromboembolism / Q000517:prevention & control*; D013997:Time Factors; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D014859:Warfarin