title: Risk of recurrent venous thromboembolism among deep vein thrombosis and pulmonary embolism patients treated with warfarin.
abstract: OBJECTIVE
  Guidelines for warfarin treatment of venous thromboembolism (VTE) recommend targeting an international normalized ratio (INR) level of 2-3. This study examines the association between INR levels and VTE recurrence among warfarin-treated patients.
  
  
  METHODS
  A retrospective cohort study in the MedMining electronic health record database included adults treated with warfarin for VTE in 2004-2011. INR levels during warfarin use were categorized as below therapeutic range (<2), in range (2-3), or above range (>3), with time in each category estimated using the Rosendaal method. Recurrent VTE was noted from 30 days after the initial VTE to end of follow-up, which ranged up to 8 years. The incidence of recurrent VTE was calculated, and association with time-varying INR levels estimated using Cox models.
  
  
  RESULTS
  Of 1753 qualifying patients, 867 had deep vein thrombosis, and 886 had pulmonary embolism. Mean age was 58 years, and 50.7% were female. Across all follow-up time, VTE recurrences were observed in 134 (7.6%) patients, at a rate of 3.2 (95% confidence interval [CI]: 0.7-9.1) events per 100 person-years. The risk of VTE recurrence was greater during time spent with INR <2 than with INR in the therapeutic range (hazard ratio [HR]: 3.37; 95% CI: 2.16-5.27). Low platelet counts also predicted greater risk of VTE recurrence (HR: 2.13; 95% CI: 1.24-3.67).
  
  
  CONCLUSIONS
  Exposure to warfarin and other anticoagulants was estimated based on prescription data and may be inaccurate. The study data include care within a single health system; thus, care received outside of the health system may be missing, and results may not be generalizable to the broader US population.
  
  
  CONCLUSIONS
  Approximately 8% of patients experienced a recurrent VTE during follow-up. Subtherapeutic INR levels were associated with a more than three-fold increased risk of VTE recurrence.
authors.affiliation: Evidera , Lexington, MA , USA.
authors.forename: Beth L
authors.initials: BL
authors.lastname: Nordstrom
authors.forename: Michael A
authors.initials: MA
authors.lastname: Evans
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Edith A
authors.initials: EA
authors.lastname: Nutescu
authors.forename: Jeff R
authors.initials: JR
authors.lastname: Schein
authors.forename: Brahim K
authors.initials: BK
authors.lastname: Bookhart
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D016208:Databases, Factual; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015994:Incidence; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011655:Pulmonary Embolism / Q000188:drug therapy; D012189:Retrospective Studies; D018570:Risk Assessment; D055502:Secondary Prevention / Q000379:methods / Q000706:statistics & numerical data; D054556:Venous Thromboembolism / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000188:drug therapy*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: Deep vein thrombosis; International normalized ratio; Pulmonary embolism; Venous thromboembolism; Warfarin