title: Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the veterans health administration.
abstract: BACKGROUND
  Dabigatran is a novel oral anti-coagulant (NOAC) that reduces risk of stroke in patients with non-valvular atrial fibrillation (NVAF). It does not require routine monitoring with laboratory testing which may have an adverse impact on adherence. We aimed to describe adherence to dabigatran in the first year after initiation and assess the association between non-adherence to dabigatran and clinical outcomes in a large integrated healthcare system.
  
  
  METHODS
  We studied a national cohort of 5,376 patients with NVAF, initiated on dabigatran between October-2010 and September-2012 at all Veterans Affairs hospitals. Adherence to dabigatran was calculated as proportion of days covered (PDC) and association between PDC and outcomes was assessed using standard regression techniques.
  
  
  RESULTS
  Mean age of the study cohort was 71.3 ± 9.7 years; 98.3% were men and mean CHADS2 score was 2.4 ± 1.2 (mean CHA2DS2VASc score 3.2 ± 1.4). Median PDC was 94% (IQR 76%-100%; mean PDC 84% ± 22%) over a median follow-up of 244 days (IQR 140-351). A total of 1,494 (27.8%) patients had a PDC <80% and were classified as non-adherent. After multivariable adjustment, lower adherence was associated with increased risk for combined all-cause mortality and stroke (HR 1.13, 95% CI 1.07-1.19 per 10% decrease in PDC). Adherence to dabigatran was not associated with non-fatal bleeding or myocardial infarction.
  
  
  CONCLUSIONS
  In the year after initiation, adherence to dabigatran for a majority of patients is very good. However, 28% of patients in our cohort had poor adherence. Furthermore, lower adherence to dabigatran was associated with increased adverse outcomes. Concerted efforts are needed to optimize adherence to NOACs.
authors.affiliation: Veterans Affairs Eastern Colorado Health Care System, Denver, CO; University of Colorado-School of Medicine, Aurora, CO; Colorado Cardiovascular Outcomes Research Consortium, Denver, CO.
authors.forename: Supriya
authors.initials: S
authors.lastname: Shore
authors.affiliation: Veterans Affairs Eastern Colorado Health Care System, Denver, CO; Colorado Cardiovascular Outcomes Research Consortium, Denver, CO; University of Colorado-School of Public Health, Aurora, CO.
authors.forename: Evan P
authors.initials: EP
authors.lastname: Carey
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; Stanford University School of Medicine, Stanford, CA.
authors.forename: Mintu P
authors.initials: MP
authors.lastname: Turakhia
authors.affiliation: Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, CA; Western University of Health Sciences, Pomona, CA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Jackevicius
authors.affiliation: Veterans Affairs, Pharmacy Benefits Management Services and Center for Medication Safety, Hines, IL.
authors.forename: Fran
authors.initials: F
authors.lastname: Cunningham
authors.affiliation: McGill University Health Center, Montréal, Québec, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Pilote
authors.affiliation: Veterans Affairs Eastern Colorado Health Care System, Denver, CO; University of Colorado-School of Medicine, Aurora, CO; Colorado Cardiovascular Outcomes Research Consortium, Denver, CO.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Bradley
authors.affiliation: Veterans Affairs Eastern Colorado Health Care System, Denver, CO; University of Colorado-School of Medicine, Aurora, CO; Colorado Cardiovascular Outcomes Research Consortium, Denver, CO.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Maddox
authors.affiliation: Veterans Affairs Eastern Colorado Health Care System, Denver, CO; University of Colorado-School of Public Health, Aurora, CO.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Grunwald
authors.affiliation: University of Colorado-School of Public Health, Aurora, CO.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Barón
authors.affiliation: Veterans Affairs Eastern Colorado Health Care System, Denver, CO; University of Colorado-School of Medicine, Aurora, CO; Colorado Cardiovascular Outcomes Research Consortium, Denver, CO.
authors.forename: John S
authors.initials: JS
authors.lastname: Rumsfeld
authors.affiliation: Veterans Affairs Eastern Colorado Health Care System, Denver, CO; University of Colorado-School of Medicine, Aurora, CO; Colorado Cardiovascular Outcomes Research Consortium, Denver, CO.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Varosy
authors.affiliation: Veterans Affairs Eastern Colorado Health Care System, Denver, CO; University of Colorado-School of Medicine, Aurora, CO; Colorado Cardiovascular Outcomes Research Consortium, Denver, CO.
authors.forename: Preston M
authors.initials: PM
authors.lastname: Schneider
authors.affiliation: Veterans Affairs Eastern Colorado Health Care System, Denver, CO; University of Colorado-School of Medicine, Aurora, CO; Colorado Cardiovascular Outcomes Research Consortium, Denver, CO.
authors.forename: Lucas N
authors.initials: LN
authors.lastname: Marzec
authors.affiliation: Veterans Affairs Eastern Colorado Health Care System, Denver, CO; University of Colorado-School of Medicine, Aurora, CO; Colorado Cardiovascular Outcomes Research Consortium, Denver, CO. Electronic address: michael.ho@va.gov.
authors.forename: P Michael
authors.initials: PM
authors.lastname: Ho
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications; D001562:Benzimidazoles / Q000627:therapeutic use*; D015331:Cohort Studies; D000069604:Dabigatran; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000517:prevention & control*; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome; D014481:United States; D014493:United States Department of Veterans Affairs; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016903:Drug Monitoring
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D000069604:Dabigatran