title: Factors affecting time to maintenance dose in patients initiating warfarin.
abstract: OBJECTIVE
  Patients starting warfarin often experience lengthy dose-titration periods, when they are at high risk for bleeding and thromboembolism. However, relatively little is known about why some patients take longer than others to reach maintenance dose. Thus, we sought to identify social, clinical, and genetic factors associated with prolonged time to maintenance dose (TTM).
  
  
  METHODS
  We conducted a time-to-event analysis, using a prospective cohort of patients initiating warfarin (N = 390). Additionally, we examined whether changes in post-initiation factors were associated with TTM. Finally, we performed a secondary analysis in a subcohort (N = 156) assessing the effect of adherence on TTM.
  
  
  RESULTS
  No genetic or post-initiation factors were significantly associated with TTM. However, previous use of warfarin [hazard ratio (HR) = 0.64; 95% confidence interval (CI) 0.46, 0.88], current smoking status (HR = 0.61; 95%CI 0.39, 0.96), fewer than four doctor's visits in the previous year (HR = 0.63 vs 4-12 visits; 95%CI 0.46, 0.88), and worse general health status (HR = 0.63; 95%CI 0.47, 0.84) were significantly associated with longer TTM. Use of illegal injectable drugs (HR = 2.51; 95%CI 1.17, 5.39) was associated with shorter TTM. On secondary analysis, the HR for better adherence and TTM was 1.70 (95%CI 0.88, 3.27).
  
  
  CONCLUSIONS
  Time to maintenance dose was associated with pre-existing behavioral factors, health care utilization, and health quality but not clinical comorbidities or genetic factors in patients initiating warfarin. Future studies are needed to determine whether warfarin patients with prolonged TTM would have better outcomes on alternative agents.
authors.affiliation: Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Finkelman
authors.forename: Benjamin
authors.initials: B
authors.lastname: French
authors.forename: Luanne
authors.initials: L
authors.lastname: Bershaw
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kimmel
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D010342:Patient Acceptance of Health Care / Q000523:psychology; D011446:Prospective Studies; D013997:Time Factors; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: pharmacoepidemiology; pharmacogenetics; race; survival analysis; treatment effectiveness; warfarin