title: Early non-persistence with dabigatran and rivaroxaban in patients with atrial fibrillation.
abstract: Dabigatran and rivaroxaban are novel oral anticoagulants (NOACs) approved for stroke prevention in atrial fibrillation (AF). Although NOACs are more convenient than warfarin, their lack of monitoring may predispose patients to non-persistence. Limited information is available on NOAC non-persistence rates and related clinical outcomes in clinical practice.
  
  
  
  We conducted a retrospective cohort study using administrative data from Ontario, Canada, from January 1998 to March 2014 of patients with AF who were dispensed dabigatran or rivaroxaban. Non-persistence was defined as a gap in dabigatran or rivaroxaban prescriptions ≥14 days. A multivariable Cox proportional hazards model was used to estimate the primary composite outcome of stroke, transient ischaemic attack (TIA) and mortality associated with non-persistence.
  
  
  
  The cohort consisted of 15 857 dabigatran (age 80.7±6.7 year) and 10 119 rivaroxaban users (age 77.0±7.1 year) with women comprising 52% of each medication group. At 6 months, 36.4% of patients were non-persistent to dabigatran, while 31.9% of patients were non-persistent to rivaroxaban. Stroke/TIA/death was significantly higher for those non-persistent to dabigatran (HR 1.76 (95% CI 1.60 to 1.94); p<0.0001) or rivaroxaban (HR 1.89 (95% CI 1.64 to 2.19); p<0.0001) compared with those who were persistent. Risk of stroke/TIA was markedly higher in non-persistent patients to dabigatran (HR 3.75 (95% CI 2.59 to 5.43); p<0.0001) and rivaroxaban (HR 6.25 (95% CI 3.37 to 11.58); p<0.0001) than those persistent.
  
  
  
  NOAC non-persistence rates are high in clinical practice, with approximately one in three patients becoming non-persistent to dabigatran or rivaroxaban within 6 months after drug initiation. Non-persistence with either dabigatran or rivaroxaban is significantly associated with worse clinical outcomes of stroke/TIA/death.
authors.affiliation: Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, California, USA.|Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.|Department of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto, Toronto, Canada.|Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.|University Health Network, Toronto, Ontario, Canada.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Jackevicius
authors.affiliation: Division of Cardiology, McGill University Health Centre, Montreal, Quebec, Canda.
authors.forename: Meytal Agvil
authors.initials: MA
authors.lastname: Tsadok
authors.affiliation: Division of Clinical Epidemiology, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Vidal
authors.initials: V
authors.lastname: Essebag
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.|Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Clare
authors.initials: C
authors.lastname: Atzema
authors.affiliation: Division of Cardiology, McGill University Health Centre, Montreal, Quebec, Canda.|Division of Clinical Epidemiology, Jewish General Hospital/McGill University, Quebec, Canada.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Eisenberg
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.|Department of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto, Toronto, Canada.|Division of Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
authors.forename: Jack V
authors.initials: JV
authors.lastname: Tu
authors.affiliation: Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, California, USA.|Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Lu
authors.affiliation: Division of Cardiology, McGill University Health Centre, Montreal, Quebec, Canda.
authors.forename: Elham
authors.initials: E
authors.lastname: Rahme
authors.affiliation: Division of Cardiology, University of Colorado, Aurora, Colorado, USA.|Veterans Affairs Eastern Colorado Health Care System, Denver, Colorado, USA.
authors.forename: P Michael
authors.initials: PM
authors.lastname: Ho
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.|Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Mintu
authors.initials: M
authors.lastname: Turakhia
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Karin H
authors.initials: KH
authors.lastname: Humphries
authors.affiliation: Division of Cardiology, McGill University Health Centre, Montreal, Quebec, Canda.
authors.forename: Hassan
authors.initials: H
authors.lastname: Behlouli
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
authors.forename: Limei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Division of Cardiology, McGill University Health Centre, Montreal, Quebec, Canda.|Division of General Internal Medicine, McGill University and Research institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Pilote
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000150:complications* / Q000188:drug therapy; D000069604:Dabigatran / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D009864:Ontario / Q000453:epidemiology; D012042:Registries; D012189:Retrospective Studies; D000069552:Rivaroxaban / Q000008:administration & dosage*; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000991:Antithrombins; D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban; D000069604:Dabigatran
keywords: Atrial fibrillation; Cardiac arrhythmias; Diseases; Health services; Medication adherence; Quality and outcomes of care; Research approaches; Resuscitation science