title: Single-dose adjustment versus no adjustment of warfarin in stably anticoagulated patients with an occasional international normalized ratio (INR) out of range.
abstract: BACKGROUND
  Well-controlled patients on warfarin may still have occasional International Normalized Ratios (INRs) outside the therapeutic range. It is unclear whether there is any benefit of a single-dose correction in this situation.
  
  
  OBJECTIVE
  To evaluate whether patients with very stable INR results should continue with the maintenance dose of warfarin without a single-dose correction, even when the result unexpectedly is moderately below or above the therapeutic range.
  
  
  METHODS
  A) We reviewed retrospectively 364 patients with unchanged maintenance dose for at least 6 months and an occasional INR outside the therapeutic range regarding decision on dosing and the effect on the next INR. B) We randomized 160 patients with at least 3 months of unchanged maintenance dose, an occasional INR deviating to a minimum of 1.5 or a maximum of 4.4 and unexplained or temporary, removable cause to a single-dose Change or No change. Follow-up INRs and telephone interviews were obtained after 2 weeks.
  
  
  RESULTS
  A) Retrospectively, the proportion of follow-up INRs outside the therapeutic range was 29.9% after No change, 27.1% after Increased dose and 25.7% after Skipped/reduced dose. However, the decision on No change was mainly taken in case of minimal INR deviations. B) Forty-eight (60%) of the patients randomized to Change were within the therapeutic range at follow-up versus 45 (56%) of those with No change, odds ratio 1.17 (95% confidence interval 0.59-2.30). For baseline INRs deviating down to 1.6 or up to 3.6 (therapeutic range, INR 2.0-3.0) the 2-week INRs did not differ between the groups.
  
  
  CONCLUSIONS
  Our results suggest only a small or no difference between the two managements of an occasional INR out of range in terms of the 2-week follow-up INR. In stable patients on warfarin with an occasional INR outside the therapeutic range it seems reasonable to continue with the same dose without a single-dose change and perform a repeat test in about 2 weeks. (ClinicalTrials.gov number, NCT00814177.).
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada. schulms@mcmaster.ca
authors.forename: S
authors.initials: S
authors.lastname: Schulman
authors.forename: A
authors.initials: A
authors.lastname: Melinyshyn
authors.forename: D
authors.initials: D
authors.lastname: Ennis
authors.forename: L
authors.initials: L
authors.lastname: Rudd-Scott
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods*; D008297:Male; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin