title: Adherence to Rivaroxaban, Dabigatran, and Apixaban for Stroke Prevention in Incident, Treatment-Naïve Nonvalvular Atrial Fibrillation.
abstract: BACKGROUND
  Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used for prevention of stroke secondary to nonvalvular atrial fibrillation (NVAF). Increased use of NOACs is partially a result of simplified regimens compared with warfarin, which has been associated with poor adherence and persistence to therapy. Few studies have assessed adherence to NOACs, especially using contemporary data now that multiple NOACs are available.
  
  
  OBJECTIVE
  To evaluate adherence to NOACs in a cohort of newly diagnosed NVAF patients who are commercially insured.
  
  
  METHODS
  Incident, treatment-naïve NVAF patients were identified in 2013 from a large claims database. Patients were included who initiated rivaroxaban, dabigatran, or apixaban within 30 days after diagnosis. Subjects were required to have 12 months of pre-index information to assess demographic and clinical characteristics (comorbidities, CHA2DS2-VASc, and HAS-BLED scores). Adherence to the index medication and adherence to any oral anticoagulant was assessed using proportion of days covered (PDC) at 3, 6, and 9 months. The number of switches and gaps in therapy were also evaluated. Analyses were stratified by stroke risk scores, and a logistic regression model was used to control for factors that may predict high adherence (PDC ≥ 0.80).
  
  
  RESULTS
  A total of 3,455 rivaroxaban, 1,264 dabigatran, and 504 apixaban users were included with no major clinical or demographic differences between groups. At 3, 6, and 9 months of follow-up, dabigatran had lower adherence (PDC = 0.77, 0.67, and 0.62) compared with rivaroxaban (PDC = 0.84, 0.75, and 0.70; P < 0.001) and apixaban (PDC = 0.82, 0.75, and 0.71; P < 0.001), as well as nearly twice the number of switches to either other anticoagulants or antiplatelet therapy. At 9 months, 55.0% of rivaroxaban initiators had PDC ≥ 0.80, which was comparable with 56.8% for apixaban and significantly greater than 46.7% for dabigatran (P < 0.001). Adherence was higher overall as stroke risk increased and showed dabigatran had consistently lower adherence compared with the other NOACs. Overall adherence to any oral anticoagulants, allowing for switches to another NOAC or warfarin, was not dependent on the index medication (9-month PDC = 0.74, 0.71, and 0.74 for rivaroxaban, dabigatran, and apixaban initiators). Adjusted analyses showed that increasing age and comorbid hypertension and diabetes were associated with higher adherence. Compared with rivaroxaban, dabigatran initiators had nearly 30% lower odds of being adherent to their index medication, and no differences were observed between apixaban and rivaroxaban. At 9 months, there were no differences between NOACs for overall adherence to oral anticoagulants.
  
  
  CONCLUSIONS
  In this real-world analysis of adherence to NOACs, rivaroxaban and apixaban had favorable profiles compared with dabigatran, and rivaroxaban appeared to have higher overall adherence among the NOACs. Clinicians and managed care organizations should consider the implications of lower adherence on clinical outcomes as well as quality assessment.
  
  
  BACKGROUND
  The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1TR000117. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Brown reports receiving a training fellowship from Human and Pfizer. Study concept and design were contributed by Brown and Shewale. Talbert took the lead in data collection, along with Brown, and data interpretation was primarily performed by Brown, along with Shewale. The manuscript was written primarily by Brown, along with Shewale, and revised by all the authors.
authors: 1 Institute for Pharmaceutical Outcomes & Policy, Department of Pharmacy Practice & Science, University of Kentucky College of Pharmacy, Lexington, Kentucky.
authors: Joshua D
authors: JD
authors: Brown
authors: 2 Division of Pharmaceutical Evaluation & Policy, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors: Anand R
authors: AR
authors: Shewale
authors: 1 Institute for Pharmaceutical Outcomes & Policy, Department of Pharmacy Practice & Science, University of Kentucky College of Pharmacy, Lexington, Kentucky.
authors: Jeffery C
authors: JC
authors: Talbert
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000453:epidemiology; D015331:Cohort Studies; D000069604:Dabigatran / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D007345:Insurance Claim Review; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage*; D011728:Pyridones / Q000008:administration & dosage*; D000069552:Rivaroxaban / Q000008:administration & dosage*; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D014481:United States / Q000453:epidemiology
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran