title: Out-of-range INR values and outcomes among new warfarin patients with non-valvular atrial fibrillation.
abstract: BACKGROUND
  Although efficacious in stroke prevention in non-valvular atrial fibrillation, many warfarin patients are sub-optimally managed.
  
  
  OBJECTIVE
  To evaluate the association of international normalized ratio control and clinical outcomes among new warfarin patients with non-valvular atrial fibrillation.
  
  
  METHODS
  Adult non-valvular atrial fibrillation patients (≥18 years) initiating warfarin treatment were selected from the US Veterans Health Administration dataset between 10/2007 and 9/2012.
  
  
  METHODS
  Valid international normalized ratio values were examined from the warfarin initiation date through the earlier of the first clinical outcome, end of warfarin exposure or death. Each patient contributed multiple in-range and out-of-range time periods.
  
  
  METHODS
  The relative risk ratios of clinical outcomes associated with international normalized ratio control were estimated.
  
  
  RESULTS
  34,346 patients were included for analysis. During the warfarin exposure period, the incidence of events per 100 person-years was highest when patients had international normalized ratio <2:13.66 for acute coronary syndrome; 10.30 for ischemic stroke; 2.93 for transient ischemic attack; 1.81 for systemic embolism; and 4.55 for major bleeding. Poisson regression confirmed that during periods with international normalized ratio <2, patients were at increased risk of developing acute coronary syndrome (relative risk ratio: 7.9; 95 % confidence interval 6.9-9.1), ischemic stroke (relative risk ratio: 7.6; 95 % confidence interval 6.5-8.9), transient ischemic attack (relative risk ratio: 8.2; 95 % confidence interval 6.1-11.2), systemic embolism (relative risk ratio: 6.3; 95 % confidence interval 4.4-8.9) and major bleeding (relative risk ratio: 2.6; 95 % confidence interval 2.2-3.0). During time periods with international normalized ratio >3, patients had significantly increased risk of major bleeding (relative risk ratio: 1.5; 95 % confidence interval 1.2-2.0).
  
  
  CONCLUSIONS
  In a Veterans Health Administration non-valvular atrial fibrillation population, exposure to out-of-range international normalized ratio values was associated with significantly increased risk of adverse clinical outcomes.
authors.affiliation: Health Economics & Outcomes Research (HECOR), Janssen Scientific Affairs, LLC, 1000 US Highway 202 South, Room 3264, Raritan, NJ, 08869, USA, wnelson@its.jnj.com.
authors.forename: Winnie W
authors.initials: WW
authors.lastname: Nelson
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Onur
authors.initials: O
authors.lastname: Baser
authors.forename: Chandrasekharrao V
authors.initials: CV
authors.lastname: Damaraju
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Schein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D019934:International Normalized Ratio / Q000592:standards*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014493:United States Department of Veterans Affairs / Q000639:trends; D014859:Warfarin / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin