title: Impact of global geographic region on time in therapeutic range on warfarin anticoagulant therapy: data from the ROCKET AF clinical trial.
abstract: BACKGROUND
  Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial.
  
  
  RESULTS
  TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i-TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i-TTR was 55.2% (SD 21.3%) and the median i-TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i-TTR, dominant determinants were previous warfarin use (mean i-TTR of 61.1% for warfarin-experienced versus 47.4% in VKA-naïve patients) and geographic region where patients were managed (mean i-TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i-TTRs had INR distributions shifted toward lower INR values and had longer inter-INR test intervals.
  
  
  CONCLUSIONS
  Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i-TTR in global studies of warfarin. Regional differences in mean i-TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing.
  
  
  BACKGROUND
  URL: ClinicalTrials.gov. Unique identifier: NCT00403767.
authors.affiliation: Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. dsinger@partners.org
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.forename: Anne S
authors.initials: AS
authors.lastname: Hellkamp
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.forename: Guohua
authors.initials: G
authors.lastname: Pan
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001208:Asia; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects*; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods*; D005060:Europe; D005260:Female; D054625:Healthcare Disparities; D006801:Humans; D019934:International Normalized Ratio; D016014:Linear Models; D008297:Male; D009025:Morpholines / Q000627:therapeutic use; D015999:Multivariate Analysis; D009656:North America; D011237:Predictive Value of Tests; D012111:Residence Characteristics; D000069552:Rivaroxaban; D013019:South Africa; D013020:South America; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013876:Thiophenes / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D009025:Morpholines; D013876:Thiophenes; D014859:Warfarin; D000069552:Rivaroxaban