How to Monitor Patients Receiving Direct Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Practice Tool Endorsed by Thrombosis Canada, the Canadian Stroke Consortium, the Canadian Cardiovascular Pharmacists Network, and the Canadian Cardiovascular Society
Authors: David J. Gladstone, William H. Geerts, James Douketis, Noah Ivers, Jeff S. Healey, Kori Leblanc
Journal: Annals of Internal Medicine (2015)

Ideas and Opinions1 September 2015How to Monitor Patients Receiving Direct Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Practice Tool Endorsed by Thrombosis Canada, the Canadian Stroke Consortium, the Canadian Cardiovascular Pharmacists Network, and the Canadian Cardiovascular SocietyDavid J. Gladstone, MD, PhD, William H. Geerts, MD, James Douketis, MD, Noah Ivers, MD, PhD, Jeff S. Healey, MD, and Kori Leblanc, PharmDDavid J. Gladstone, MD, PhDFrom the University of Toronto Department of Medicine; Sunnybrook Regional Stroke Prevention Clinic, Hurvitz Brain Sciences Program, Dr. Thomas and Harriet Black Rapid TIA Clinic, and Anticoagulant Management Clinic and Thromboembolism Service, Sunnybrook Health Sciences Centre; University of Toronto Stroke Program; Family Practice Health Centre, Women's College Research Institute, and Institute for Health Systems Solutions and Virtual Care, Women's College Hospital;and University Health Network and OpenLab, University Health Network, Toronto, Ontario, Canada, and McMaster University, Population Health Research Institute, and Canadian Stroke Prevention Intervention Network, Hamilton, Ontario, Canada., William H. Geerts, MDFrom the University of Toronto Department of Medicine; Sunnybrook Regional Stroke Prevention Clinic, Hurvitz Brain Sciences Program, Dr. Thomas and Harriet Black Rapid TIA Clinic, and Anticoagulant Management Clinic and Thromboembolism Service, Sunnybrook Health Sciences Centre; University of Toronto Stroke Program; Family Practice Health Centre, Women's College Research Institute, and Institute for Health Systems Solutions and Virtual Care, Women's College Hospital;and University Health Network and OpenLab, University Health Network, Toronto, Ontario, Canada, and McMaster University, Population Health Research Institute, and Canadian Stroke Prevention Intervention Network, Hamilton, Ontario, Canada., James Douketis, MDFrom the University of Toronto Department of Medicine; Sunnybrook Regional Stroke Prevention Clinic, Hurvitz Brain Sciences Program, Dr. Thomas and Harriet Black Rapid TIA Clinic, and Anticoagulant Management Clinic and Thromboembolism Service, Sunnybrook Health Sciences Centre; University of Toronto Stroke Program; Family Practice Health Centre, Women's College Research Institute, and Institute for Health Systems Solutions and Virtual Care, Women's College Hospital;and University Health Network and OpenLab, University Health Network, Toronto, Ontario, Canada, and McMaster University, Population Health Research Institute, and Canadian Stroke Prevention Intervention Network, Hamilton, Ontario, Canada., Noah Ivers, MD, PhDFrom the University of Toronto Department of Medicine; Sunnybrook Regional Stroke Prevention Clinic, Hurvitz Brain Sciences Program, Dr. Thomas and Harriet Black Rapid TIA Clinic, and Anticoagulant Management Clinic and Thromboembolism Service, Sunnybrook Health Sciences Centre; University of Toronto Stroke Program; Family Practice Health Centre, Women's College Research Institute, and Institute for Health Systems Solutions and Virtual Care, Women's College Hospital;and University Health Network and OpenLab, University Health Network, Toronto, Ontario, Canada, and McMaster University, Population Health Research Institute, and Canadian Stroke Prevention Intervention Network, Hamilton, Ontario, Canada., Jeff S. Healey, MDFrom the University of Toronto Department of Medicine; Sunnybrook Regional Stroke Prevention Clinic, Hurvitz Brain Sciences Program, Dr. Thomas and Harriet Black Rapid TIA Clinic, and Anticoagulant Management Clinic and Thromboembolism Service, Sunnybrook Health Sciences Centre; University of Toronto Stroke Program; Family Practice Health Centre, Women's College Research Institute, and Institute for Health Systems Solutions and Virtual Care, Women's College Hospital;and University Health Network and OpenLab, University Health Network, Toronto, Ontario, Canada, and McMaster University, Population Health Research Institute, and Canadian Stroke Prevention Intervention Network, Hamilton, Ontario, Canada., and Kori Leblanc, PharmDFrom the University of Toronto Department of Medicine; Sunnybrook Regional Stroke Prevention Clinic, Hurvitz Brain Sciences Program, Dr. Thomas and Harriet Black Rapid TIA Clinic, and Anticoagulant Management Clinic and Thromboembolism Service, Sunnybrook Health Sciences Centre; University of Toronto Stroke Program; Family Practice Health Centre, Women's College Research Institute, and Institute for Health Systems Solutions and Virtual Care, Women's College Hospital;and University Health Network and OpenLab, University Health Network, Toronto, Ontario, Canada, and McMaster University, Population Health Research Institute, and Canadian Stroke Prevention Intervention Network, Hamilton, Ontario, Canada.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-0143 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Anticoagulation for atrial fibrillation with direct oral anticoagulants (DOACs)—apixaban, dabigatran, edoxaban, and rivaroxaban—is one of the most powerful stroke prevention interventions (1) and is now being prescribed to millions worldwide. Guidelines, however, have focused primarily on patient selection and therapy initiation, with little guidance on patient follow-up and monitoring for these long-term therapies. Given the increasing use of these agents, their associated risks for bleeding and nonadherence (one quarter of patients in recent reports was less than 80% adherent [2–4]), the absence of routine coagulation monitoring, and variable follow-up practices, we advocate regular, standardized clinical monitoring of patients receiving these ...References1. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383:955-62. [PMID: 24315724] doi:10.1016/S0140-6736(13)62343-0 CrossrefMedlineGoogle Scholar2. Shore S, Carey EP, Turakhia MP, Jackevicius CA, Cunningham F, Pilote L, et al. Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the Veterans Health Administration. Am Heart J. 2014;167:810-7. [PMID: 24890529] doi:10.1016/j.ahj.2014.03.023 CrossrefMedlineGoogle Scholar3. Gorst-Rasmussen A, Skjøth F, Larsen TB, Rasmussen LH, Lip GY, Lane DA. Dabigatran adherence in atrial fibrillation patients during the first year after diagnosis: a nationwide cohort study. J Thromb Haemost. 2015;13:495-504. [PMID: 25594442] doi:10.1111/jth.12845 CrossrefMedlineGoogle Scholar4. Shore S, Ho PM, Lambert-Kerzner A, Glorioso TJ, Carey EP, Cunningham F, et al. Site-level variation in and practices associated with dabigatran adherence. JAMA. 2015;313:1443-50. [PMID: 25871670] doi:10.1001/jama.2015.2761 CrossrefMedlineGoogle Scholar5. Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;123:2363-72. [PMID: 21576658] doi:10.1161/CIRCULATIONAHA.110.004747 CrossrefMedlineGoogle Scholar6. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al; European Heart Rhythm Association. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013;15:625-51. [PMID: 23625942] doi:10.1093/europace/eut083 CrossrefMedlineGoogle Scholar7. Gladstone DJ, Geerts WH, Douketis J, Ivers N, Healey JS, Leblanc K. Anticoagulant Monitoring Checklist and Quick-Reference Tables for Managing Patients on Direct Oral Anticoagulants (DOACs) for Stroke Prevention in Atrial Fibrillation. Thrombosis Canada. 2015. Accessed at www.thrombosiscanada.ca on 30 June 2015. Google Scholar8. Craig HM. Accuracy of indirect measures of medication compliance in hypertension. Res Nurs Health. 1985;8:61-6. [PMID: 3846318] CrossrefMedlineGoogle Scholar9. Ewen S, Rettig-Ewen V, Mahfoud F, Böhm M, Laufs U. Drug adherence in patients taking oral anticoagulation therapy. Clin Res Cardiol. 2014;103:173-82. [PMID: 23999974] doi:10.1007/s00392-013-0616-8 CrossrefMedlineGoogle Scholar10. Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood. 2012;120:2954-62. [PMID: 22932800] doi:10.1182/blood-2012-06-415943 CrossrefMedlineGoogle Scholar11. Gladstone DJ, Bui E, Fang J, Laupacis A, Lindsay MP, Tu JV, et al. Potentially preventable strokes in high-risk patients with atrial fibrillation who are not adequately anticoagulated. Stroke. 2009;40:235-40. [PMID: 18757287] doi:10.1161/STROKEAHA.108.516344 CrossrefMedlineGoogle Scholar12. Rosenbaum L. Beyond belief—how people feel about taking medications for heart disease. N Engl J Med. 2015;372:183-7. [PMID: 25564902] doi:10.1056/NEJMms1409015 CrossrefMedlineGoogle Scholar13. Di Minno A, Spadarella G, Tufano A, Prisco D, Di Minno G. Ensuring medication adherence with direct oral anticoagulant drugs: lessons from adherence with vitamin K antagonists (VKAs). Thromb Res. 2014;133:699-704. [PMID: 24525314] doi:10.1016/j.thromres.2014.01.016 CrossrefMedlineGoogle Scholar14. Arima H, Anderson C, Omae T, Woodward M, MacMahon S, Mancia G, et al; Perindopril Protection Against Recurrent Stroke Study (PROGRESS) Collaborative Group. Effects of blood pressure lowering on intracranial and extracranial bleeding in patients on antithrombotic therapy: the PROGRESS trial. Stroke. 2012;43:1675-7. [PMID: 22535269] doi:10.1161/STROKEAHA.112.651448 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From the University of Toronto Department of Medicine; Sunnybrook Regional Stroke Prevention Clinic, Hurvitz Brain Sciences Program, Dr. Thomas and Harriet Black Rapid TIA Clinic, and Anticoagulant Management Clinic and Thromboembolism Service, Sunnybrook Health Sciences Centre; University of Toronto Stroke Program; Family Practice Health Centre, Women's College Research Institute, and Institute for Health Systems Solutions and Virtual Care, Women's College Hospital;and University Health Network and OpenLab, University Health Network, Toronto, Ontario, Canada, and McMaster University, Population Health Research Institute, and Canadian Stroke Prevention Intervention Network, Hamilton, Ontario, Canada.Acknowledgment: The authors thank Dr. Ken Gruchalla (Health Canada) for valuable comments on an earlier draft and Najla Nina Zahr (OpenLab, University Health Network, Toronto) for graphic design assistance for the checklist. The authors also thank numerous external reviewers, clinic nurses, and members of national professional organizations for the feedback received on earlier drafts. Dr. Gladstone thanks the Division of Neurology and Department of Medicine of Sunnybrook Health Sciences Centre and the University of Toronto.Grant Support: This article and the accompanying checklist were conceived, developed, authored, and revised by the authors as an investigator-initiated academic project, independent of industry, and refined through pilot-testing in outpatient clinics. Dr. Gladstone's research program is supported by the Bastable-Potts Chair in Stroke Research at Sunnybrook Health Sciences Centre, the Sunnybrook Department of Medicine Research Committee, the University of Toronto Department of Medicine Eaton Scholar Award, the Sam Sorbara Charitable Foundation, and the Heart and Stroke Foundation Canadian Partnership for Stroke Recovery. Dr. Ivers is funded by a Canadian Institutes of Health Research New Investigator Award in Community-Based Primary Health Care and a New Investigator Award from the Department of Family and Community Medicine, University of Toronto.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0143.Corresponding Author: David J. Gladstone, MD, PhD, Regional Stroke Prevention Clinic, Sunnybrook Health Sciences Centre, A442-2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada; e-mail, david.[email protected]ca.Current Author Addresses: Dr. Gladstone: Regional Stroke Prevention Clinic, Sunnybrook Health Sciences Centre, A442-2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.Dr. Geerts: Sunnybrook Health Sciences Centre, Room D764, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.Dr. Douketis: St. Joseph's Healthcare Hamilton, Room F-544, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.Dr. Ivers: Women's College Hospital Family Practice, 76 Grenville Street, Toronto, Ontario M5S 1B2, Canada.Dr. Healey: Room C3-121, DBCVSRI Building, Hamilton Health Sciences, General Site, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.Dr. Leblanc: Pharmacy Department, 585 University Avenue, Clinical Services Building, BCS-080, Toronto, Ontario M5G 2N2, Canada.Author Contributions: Conception and design: D.J. Gladstone, K. Leblanc.Analysis and interpretation of the data: D.J. Gladstone, J. Douketis, N. Ivers, K. Leblanc.Drafting of the article: D.J. Gladstone, W.H. Geerts, J. Douketis, N. Ivers, K. Leblanc.Critical revision of the article for important intellectual content: D.J. Gladstone, W.H. Geerts, J. Douketis, J.S. Healey, K. Leblanc.Final approval of the article: D.J. Gladstone, W.H. Geerts, J. Douketis, N. Ivers, J.S. Healey, K. Leblanc.Administrative, technical, or logistic support: N. Ivers, K. Leblanc.Collection and assembly of data: D.J. Gladstone, N. Ivers, K. Leblanc.This article was published online first at www.annals.org on 30 June 2015. 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