title: Stroke associated with discontinuation of warfarin therapy for atrial fibrillation.
abstract: OBJECTIVE
  The objective of this study was to determine the association between warfarin discontinuation and stroke among patients with nonvalvular atrial fibrillation (NVAF).
  
  
  METHODS
  This was a retrospective, observational study of adult NVAF patients (≥ 18 years) who were on warfarin in the Truven MarketScan commercial claims and encounters and Medicare supplemental and coordination of benefits databases (1 January 2008 to 30 June 2012). Warfarin discontinuation was defined as a gap of ≥ 45 days in warfarin prescription within 1 year after initiation. Patients who did and did not discontinue warfarin were matched at a 1:1 ratio using a propensity score method. Matched patients were followed for up to 1 year to determine risks of ischemic stroke, transient ischemic attack (TIA), and hemorrhagic stroke. A multivariate Cox proportional hazards model was used to further adjust for the effects of potential confounders.
  
  
  RESULTS
  A total of 27,000 patients were included. Patients who discontinued warfarin had higher rates of ischemic stroke compared to persistent patients (1.0 vs. 0.5 per 100 patient years, P < 0.01), but similar rates of TIA (1.2 vs. 0.9 per 100 patient years, respectively; P = 0.07) and hemorrhagic stroke (0.3 vs. 0.2 per 100 patient years, P = 0.31). After adjustment for potential confounders, warfarin discontinuation was significantly associated with increased risk of ischemic stroke (hazard ratio [HR]: 2.04; 95% confidence interval [CI]: 1.47-2.84), TIA (HR: 1.36; 95% CI: 1.04-1.78), and ischemic stroke or TIA (HR: 1.50; 95% CI: 1.20-1.87).
  
  
  CONCLUSIONS
  Warfarin discontinuation is associated with increased risk of ischemic stroke and TIA. Health care providers may need to take a more active role in the management of warfarin discontinuation and clinical outcomes, e.g., by considering newer anticoagulants with favorable risk-benefit profiles. Key limitations of the study include unavailability of important clinical factors and measures in claims data.
authors.affiliation: a a University of Tennessee College of Pharmacy , Memphis , TN , USA.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Spivey
authors.affiliation: a a University of Tennessee College of Pharmacy , Memphis , TN , USA.|b b Global Health Economics & Outcomes Research, Pfizer Inc. , New York , NY , USA.
authors.forename: Xianchen
authors.initials: X
authors.lastname: Liu
authors.affiliation: a a University of Tennessee College of Pharmacy , Memphis , TN , USA.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: c c Statistics, Pfizer Inc. , New York , NY , USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Mardekian
authors.affiliation: a a University of Tennessee College of Pharmacy , Memphis , TN , USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Parker
authors.affiliation: d d Global Health Economics & Outcomes Research , Bristol-Myers Squibb, Princeton , NJ , USA.
authors.forename: Hemant
authors.initials: H
authors.lastname: Phatak
authors.affiliation: e e Global Health Economics & Outcomes Research, Pfizer Inc. , New York , NY , USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Masseria
authors.affiliation: d d Global Health Economics & Outcomes Research , Bristol-Myers Squibb, Princeton , NJ , USA.
authors.forename: Sumesh
authors.initials: S
authors.lastname: Kachroo
authors.affiliation: f f Global Medical Affairs, Pfizer Inc. , New York , NY , USA.
authors.forename: Younos
authors.initials: Y
authors.lastname: Abdulsattar
authors.affiliation: a a University of Tennessee College of Pharmacy , Memphis , TN , USA.
authors.forename: Junling
authors.initials: J
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology; D014859:Warfarin / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: Atrial fibrillation; Discontinuation; Persistence; Stroke; Warfarin therapy