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Original research article
Early non-persistence with dabigatran and rivaroxaban in patients with atrial fibrillation
  1. Cynthia A Jackevicius1,2,3,4,5,
  2. Meytal Agvil Tsadok6,
  3. Vidal Essebag7,
  4. Clare Atzema2,8,
  5. Mark J Eisenberg6,9,
  6. Jack V Tu2,3,10,
  7. Lingyun Lu1,4,
  8. Elham Rahme6,
  9. P Michael Ho11,12,
  10. Mintu Turakhia13,14,
  11. Karin H Humphries15,
  12. Hassan Behlouli6,
  13. Limei Zhou2,
  14. Louise Pilote6,16
  1. 1 Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, California, USA
  2. 2 Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
  3. 3 Department of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto, Toronto, Canada
  4. 4 Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA
  5. 5 University Health Network, Toronto, Ontario, Canada
  6. 6 Division of Cardiology, McGill University Health Centre, Montreal, Quebec, Canda
  7. 7 Division of Clinical Epidemiology, McGill University Health Centre, Montreal, Quebec, Canada
  8. 8 Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  9. 9 Division of Clinical Epidemiology, Jewish General Hospital/McGill University, Quebec, Canada
  10. 10 Division of Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
  11. 11 Division of Cardiology, University of Colorado, Aurora, Colorado, USA
  12. 12 Veterans Affairs Eastern Colorado Health Care System, Denver, Colorado, USA
  13. 13 Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
  14. 14 Stanford University School of Medicine, Stanford, California, USA
  15. 15 University of British Columbia, Vancouver, British Columbia, Canada
  16. 16 Division of General Internal Medicine, McGill University and Research institute of the McGill University Health Centre, Montreal, Quebec, Canada
  1. Correspondence to Dr Cynthia A Jackevicius, Department of Pharmacy Practice and Administration, Western University of Health Sciences, College of Pharmacy, 309 E. Second St., Pomona CA 91766, USA; cjackevicius{at}


Objective 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.

Methods 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.

Results 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.

Conclusions 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.

  • Atrial fibrillation
  • Medication adherence
  • Quality and outcomes of care
  • Cardiac arrhythmias
  • Resuscitation science
  • Diseases
  • Health services
  • Research approaches

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  • Contributors Study concept and design: CAJ, LP. Acquisition of data, integrity of data and accuracy of the data analysis, drafting of the manuscript and study supervision: CAJ. Analysis and interpretation of data: CAJ, LP, MAT, VE, MJE, ER, KHH, JVT, CA, MJE, LL, PMH, MT, HB, and LZ. Critical revision of the manuscript for important intellectual content: CAJ, LP, MAT, VE, MJE, ER, KHH, JVT, CA, MJE, LL, PMH, MT, HB, and LZ. Statistical analysis: LZ. Obtaining funding: CAJ, LP.

  • Funding LP is a James McGill Professor at McGill University. JVT is supported by a Canada Research Chair in Health Services Research and an Eaton Scholar award. MAT has received a fellowship award from CIHR. VE is supported by a Clinician Scientist award from the Canadian Institutes of Health Research. This study was funded by grant DC0190GP from CIHR and from grant 12GRNT8640001 American Heart Association.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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