Adherence to oral anticoagulant therapy in patients with atrial fibrillation

Valeria Raparelli; Marco Proietti; Roberto Cangemi; Gregory Y. H. Lip; Deirdre A. Lane; Stefania Basili

doi:10.1160/TH16-10-0757

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2017; 117(02): 209-218
DOI: 10.1160/TH16-10-0757

Review Article

Schattauer GmbH

Adherence to oral anticoagulant therapy in patients with atrial fibrillation

Focus on non-vitamin K antagonist oral anticoagulants

Valeria Raparelli^*

¹Department of Experimental Medicine, Sapienza-University of Rome, Rome, Italy

,

Marco Proietti^*

²Department of Internal Medicine and Medical Specialties, Sapienza-University of Rome, Rome, Italy

³University of Birmingham, Institute of Cardiovascular Sciences, City Hospital, Birmingham, UK

,

Roberto Cangemi

²Department of Internal Medicine and Medical Specialties, Sapienza-University of Rome, Rome, Italy

,

Gregory Y. H. Lip

³University of Birmingham, Institute of Cardiovascular Sciences, City Hospital, Birmingham, UK

⁴Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

,

Deirdre A. Lane^#

³University of Birmingham, Institute of Cardiovascular Sciences, City Hospital, Birmingham, UK

,

Stefania Basili^#

²Department of Internal Medicine and Medical Specialties, Sapienza-University of Rome, Rome, Italy

⁵Research Center on Gender and Evaluation and Promotion of Quality in Medicine (CEQUAM), Sapienza-University of Rome, Rome, Italy

› Author Affiliations

Abstract

Summary

Oral anticoagulation is pivotal in the management of thromboembolic risk in non-valvular atrial fibrillation (NVAF) patients. Effective anticoagulation is important to avoid major adverse events and medication adherence is central to achieve good anticoagulation control. Non-vitamin K antagonist oral anticoagulants (NOACs) are as effective and safe as vitamin K antagonist (VKAs) in NVAF patients. Due to the absence of routine anticoagulation monitoring with NOACs treatment, concerns have been raised about patient’s adherence to NOACs and real-life data demonstrates variability in adherence and persistence. A multi-level approach, including patients’ preferences, factors determining physicians’ prescribing habits and healthcare system infrastructure and support, is warranted to improve initiation and adherence of anticoagulants. Adherence to NOACs is paramount to achieve a clinical benefit. Implementation of educational programs and easy-to-use tools to identify patients most likely to be non-adherent to NOACs, are central issues in improving the quality of NVAF anticoagulation management.

Note: The review process for this manuscript was fully handled by C. Weber, Editor in Chief.

Keywords

Atrial fibrillation - Oral anticoagulation - non-vitamin K antagonist oral anticoagulants - adherence - persistence

Full Text

References

References
1 Lip GYH, Lane DA.. Stroke Prevention in Atrial Fibrillatio. J Am Med Assoc 2015; 313: 1950-1962.
2 Krueger KP. et al. Medication adherence and persistence: a comprehensive revie. Adv Ther 2005; 22: 313-356.
3 Osterberg L, Blaschke T.. Adherence to medicatio. N Engl J Med 2005; 353: 487-497.
4 Ho PM. et al. Medication adherence: its importance in cardiovascular outcomes. Circulation 2009; 119: 3028-3035.
5 De Geest S, Sabaté E.. Adherence to long-term therapies: Evidence for actio. Eur J Cardiovasc Nurs 2003; 02: 323.
6 Horne R. et al. Concordance, adherence and compliance in medicine taking. Rep Natl Coord Cent NHS Serv Deliv Organ. R D. 2005
7 Gomes T. et al. Persistence with therapy among patients treated with warfarin for atrial fibrillation. Arch Intern Med 2012; 172: 1687-1689.
8 Zalesak M. et al. Higher persistence in newly diagnosed nonvalvular atrial fibrillation patients treated with dabigatran versus warfarin. Circ Cardiovasc Qual Outcomes 2013; 06: 567-574.
9 Di Minno MND. et al. Direct anticoagulant drugs to overcome limitations of vitamin K antagonists. A critical appraisal of data in atrial fibrillation patients. Expert Opin Emerg Drugs 2013; 18: 9-23.
10 Vrijens B, Urquhart J.. From monitoring to vigilance about patient adherence to new oral anticoagulant. Europace 2013; 16: 149..
11 Rodriguez RA. et al. Non-adherence to new oral anticoagulants: a reason for concern during long-term anticoagulation? J Thromb Haemos. 2013; 11: 390-394.
12 Raparelli V. et al. Medication prescription and adherence disparities in non valvular atrial fibrillation patients: an Italian portrait from the ARAPACIS study. Intern Emerg Med 2014; 09: 861-870.
13 Kimmel SE.. The Influence of Patient Adherence on Anticoagulation Control With Warfari. Arch Intern Med 2007; 167: 229..
14 O’Brien EC. et al. Reasons for warfarin discontinuation in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Am Heart J 2014; 168: 487-494.
15 Lane DA. et al. Cardiac tachyarrhythmias and patient values and preferences for their management: the European Heart Rhythm Association (EHRA) consensus document endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoame. Europace 2015; euv233.
16 Camm AJ. et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33: 2719-2747.
17 Camm AJ, Kirchhof P, Lip GYH. et al. Guidelines for the management of atrial fibrillation. Eur Heart J 2010 31. 2369-2429.
18 Atrial Fibrillation: The Management of Atrial Fibrillation - PubMed - NCBI [Internet] Available fro. http://www.ncbi.nlm.nih.gov/pubmed/?term=25340239 Accessed March 2, 2015.
19 Lahaye S. et al. Evaluation of patients’ attitudes towards stroke prevention and bleeding risk in atrial fibrillation. Thromb Haemost 2014; 111: 465-473.
20 Gallagher AM. et al. Initiation and persistence of warfarin or aspirin in patients with chronic atrial fibrillation in general practice: do the appropriate patients receive stroke prophylaxis? J Thromb Haemos. 2008; 06: 1500-1506.
21 Fang MC. et al. Warfarin discontinuation after starting warfarin for atrial fibrillation. Circ Cardiovasc Qual Outcomes 2010; 03: 624-631.
22 Arnsten JH. et al. Determinants of compliance with anticoagulation: A case-control study. Am J Med 1997; 103: 11-17.
23 Schauer DP. et al. Psychosocial risk factors for adverse outcomes in patients with nonvalvular atrial fibrillation receiving warfarin. J Gen Intern Med 2005; 20: 1114-1119.
24 Cruess DG. et al. Patient Attitudinal and Behavioral Factors Associated with Warfarin Non-adherence at Outpatient Anticoagulation Clinics. Int J Behav Med 2009; 17: 33-42
25 Johnston JA. et al. Predictors of warfarin use among Ohio medicaid patients with new-onset nonvalvular atrial fibrillation. Arch Intern Med 2003; 163: 1705-1710
26 Orensky IA, Holdford DA.. Predictors of Noncompliance with Warfarin Therapy in an Outpatient Anticoagulation Clini. Pharmacotherapy 2005; 25: 1801-1808
27 Dantas GC. et al. Patients’ perspectives on taking warfarin: qualitative study in family practice. BMC Fam Pract 2004; 05: 15
28 Devereaux PJ. et al. Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. Br Med J 2001; 323: 1218-1222
29 Attaya S. et al. Study of Warfarin Patients Investigating Attitudes Toward Therapy Change (SWITCH Survey). Am J Ther 2012; 19: 432-435.
30 Palacio AM. et al. Patient values and preferences when choosing anticoagulants. Patient Prefer Adherence 2015; 09: 133-138.
31 Borg Xuereb. C. et al. Patients’ and health professionals’ views and experiences of atrial fibrillation and oral-anticoagulant therapy: a qualitative meta-synthesis. Patient Educ Couns 2012; 88: 330-337
32 Borg Xuereb. C. et al. Patients’ and physicians’ experiences of atrial fibrillation consultations and anticoagulation decision-making: a multi-perspective IPA design. Psychol Health 2015; 1-35
33 Amara W. et al. Patients’ attitude and knowledge about oral anticoagulation therapy: results of a self-assessment survey in patients with atrial fibrillation conducted by the European Heart Rhythm Association. Europace 2016; 18: 151-155
34 Di Minno. A. et al. Ensuring medication adherence with direct oral anticoagulant drugs: lessons from adherence with vitamin K antagonists (VKAs). Thromb Res 2014; 133: 699-704.
35 Giardini A. et al. Toward appropriate criteria in medication adherence assessment in older persons: Position Paper. Aging Clin Exp Res 2016; 28: 371-381.
36 Mohammed S. et al. Impact of Polypharmacy on Adherence to Evidence-Based Medication in Patients who Underwent Percutaneous Coronary Intervention. Curr Vasc Pharmacol 2016; 14: 388-393.
37 Proietti M. et al. Polypharmacy and major adverse events in atrial fibrillation: observations from the AFFIRM trial. Clin Res Cardiol 2016; 105: 412-420.
38 Piccini JP. et al. Polypharmacy and the Efficacy and Safety of Rivaroxaban versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation. Circulation 2015; 133: 352-360.
39 Bungard TJ, Ghali WA, Teo KK. et al. Why do patients with atrial fibrillation not receive warfarin? Arch Intern Me. 2000; 160: 41-46.
40 O’Brien EC. et al. Physician practices regarding contraindications to oral anticoagulation in atrial fibrillation: Findings from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. Am Heart J 2014; 167: 601-609 e1.
41 Pugh D. et al. Attitudes of physicians regarding anticoagulation for atrial fibrillation: a systematic review. Age Ageing 2011; 40: 675-683.
42 Choudhry NK, Anderson GM, Laupacis A. et al. Impact of adverse events on prescribing warfarin in patients with atrial fibrillation: matched pair analysis. Br Med J 2006; 332: 141-145.
43 Lip GYH. et al. Improved outcomes with European Society of Cardiology guideline-adherent antithrombotic treatment in high-risk patients with atrial fibrillation: a report from the EORP-AF General Pilot Registry. Europace 2015; 17: 1777-1786.
44 Alberts MJ. et al. Antithrombotic therapy for stroke prevention in non-valvular atrial fibrillation. Lancet Neurol 2012; 11: 1066-1081.
45 Wutzler A. et al. The use of direct oral anticoagulants for stroke prevention in atrial fibrillation: A study on physicians’ perspective and preferences. Int J Cardiol 2014; 175: 188-191.
46 Potpara TS. et al. How are patients with atrial fibrillation approached and informed about their risk profile and available therapies in Europe? Results of the European Heart Rhythm Association Survey. Europace 2015; 17: 468-472.
47 van Walraven. C. et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest 2006; 129: 1155-1166.
48 Oake N. et al. Frequency of adverse events in patients with poor anticoagulation: a meta-analysis. CMAJ 2007; 176: 1589-1594.
49 van Walraven. C. et al. The effect of hospitalization on oral anticoagulation control: a population-based study. Thromb Res 2007; 119: 705-714.
50 Yong CM. et al. Association of insurance type with receipt of oral anticoagulation in atrial fibrillation: an analysis of the American College of Cardiology NCDR PINNACLE registry. J Am Coll Cardiol 2016; 67: 888.
51 Connolly SJ. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
52 Patel MR. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891.
53 Granger CB. et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-992.
54 Giugliano RP. et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369: 2093-2104.
55 Connolly SJ. et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364: 806-817.
56 Villines TC. et al. A comparison of the safety and effectiveness of dabigatran and warfarin in non-valvular atrial fibrillation patients in a large healthcare system. Thromb Haemost 2015; 115: 1-9.
57 Avgil-Tsadok M. et al. Dabigatran use in elderly patients with atrial fibrillation. Thromb Haemost 2016; 115: 152-160.
58 Potpara TS.. Dabigatran in ‘real-world’ clinical practice for stroke prevention in patients with non-valvular atrial fibrillatio. Thromb Haemost 2015; 114: 1093-1098.
59 Seeger JD. et al. Safety and effectiveness of dabigatran and warfarin in routine care of patients with atrial fibrillation. Thromb Haemost 2015; 114: 1277-1289.
60 Coleman CI. et al. Medication adherence to rivaroxaban and dabigatran for stroke prevention in patients with non-valvular atrial fibrillation in the United States. Int J Cardiol 2016; 212: 171-173.
61 Schulman S. et al. Adherence to anticoagulant treatment with dabigatran in a real-world setting. J Thromb Haemost 2013; 11: 1295-1299.
62 Shore S. et al. Site-level variation in and practices associated with dabigatran adherence. J Am Med Assoc 2015; 313: 1443-1450.
63 Gorst-Rasmussen A. et al. Dabigatran adherence in atrial fibrillation patients during the first year after diagnosis: a nationwide cohort study. J Thromb Haemost 2015; 13: 495-504.
64 Beyer-Westendorf J. et al. Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost 2015; 113: 1247-1257.
65 Tsai K. et al. Adherence, persistence, and switching patterns of dabigatran etexilate. Am J Manag Care 2013; 19: e325-332.
66 Laliberté F. et al. Real-world comparative effectiveness and safety of rivaroxaban and warfarin in nonvalvular atrial fibrillation patients. Curr Med Res Opin 2014; 30: 1317-1325.
67 Nelson WW. et al. Medication persistence and discontinuation of rivaroxaban versus warfarin among patients with non-valvular atrial fibrillation. Curr Med Res Opin 2014; 30: 2461-2469.
68 Beyer-Westendorf J. et al. Drug persistence with rivaroxaban therapy in atrial fibrillation patients-results from the Dresden non-interventional oral anticoagulation registry. Europace 2015; 17: 530-538.
69 Hecker J. et al. Effectiveness and safety of rivaroxaban therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost 2016; 115: 939-949.
70 Camm AJ. et al. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 2015; ehv466.
71 ESC. ESC CONGRESS 2015 in REVIEW: Focus on Arrhythmias. 2015. Available a. http://www.nxtbook.com/nxtbooks/md_conference_express/esccongress2015_focusonarrhythmias/
72 Chatterjee S. et al. Treatment discontinuations with new oral agents for long-term anticoagulation: insights from a meta-analysis of 18 randomized trials including 101,801 patients. Mayo Clin Proc 2014; 89: 896-907.
73 Al-Khalili F. et al. The safety and persistence of non-vitamin-K-antagonist oral anticoagulants in atrial fibrillation patients treated in a well structured atrial fibrillation clinic. Curr Med Res Opin 2016; 1-7.
74 Shiga T. et al. Persistence of non-vitamin K antagonist oral anticoagulant use in Japanese patients with atrial fibrillation: A single-center observational study. J Arrhythmia 2015; 31: 339-344.
75 McHorney CA. et al. Adherence to Non-VKA Oral Anticoagulant Medications Based on the Pharmacy Quality Alliance Measure. Curr Med Res Opin 2015; 1-16.
76 Forslund T. et al. Comparison of treatment persistence with different oral anticoagulants in patients with atrial fibrillation. Eur J Clin Pharmacol 2016; 72: 329-338.
77 Martinez C. et al. Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC. A cohort study. Thromb Haemost 2015; 115: 31-39.
78 Beyer-Westendorf J. et al. Real-world persistence and adherence to oral anticoagulation for stroke risk reduction in patients with atrial fibrillation. Europace 2016; euv421.
79 Yao X. et al. Effect of Adherence to Oral Anticoagulants on Risk of Stroke and Major Bleeding Among Patients With Atrial Fibrillation. J Am Heart Assoc 2016; 05: pii: e003074.
80 Alberts MJ. et al. Association between once- and twice-daily direct oral anticoagulant adherence in nonvalvular atrial fibrillation patients and rates of ischemic stroke. Int J Cardiol 2016; 215: 11-13.
81 Vrijens B, Heidbuchel H.. Non-vitamin K antagonist oral anticoagulants: considerations on once- vs. twice-daily regimens and their potential impact on medication adherence. Europace 2015; 17: 514-523.
82 Heidbuchel H. et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015; euv309.
83 Renda G, De Caterina R.. The new oral anticoagulants in atrial fibrillation: once daily or twice daily. Vascul Pharmacol 2013; 59: 53-62.
84 Wan Y. et al. Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Circ Cardiovasc Qual Outcomes 2008; 01: 84-91.
85 Hylek EM.. Vitamin K antagonists and time in the therapeutic range: implications, challenges, and strategies for improvemen. J Thromb Thrombolysis 2013; 35: 333-335.
86 Gallego P, Roldan V, Marín F. et al. Cessation of oral anticoagulation in relation to mortality and the risk of thrombotic events in patients with atrial fibrillation. Thromb Haemost 2013; 110: 1189-1198.
87 Gallagher AM. et al. Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Thromb Haemost 2011; 106: 968-977.
88 De Caterina. R. et al. Vitamin K antagonists in heart disease: Current status and perspectives (Section III). Thromb Haemost 2013; 110: 1087-1107.
89 Apostolakis S. et al. Factors affecting quality of anticoagulation control among patients with atrial fibrillation on warfarin: the SAMe-TT2R2 score. Chest 2013; 144: 1555-1563.
90 Poli D. et al. A prospective validation of the SAME-TT2R2 score: how to identify atrial fibrillation patients who will have good anticoagulation control on warfarin. Intern Emerg Med 2014; 09: 443-447.
91 Gallego P. et al. SAMe-TT2R2 Score, Time in Therapeutic Range, and Outcomes in Anticoagulated Patients with Atrial Fibrillation. Am J Med 2014; 127: 1083-1088.
92 Abumuaileq RR-. Y. et al. Evaluation of SAMe-TT2R2 risk score for predicting the quality of anticoagulation control in a real-world cohort of patients with non-valvular atrial fibrillation on vitamin-K antagonists. Europace 2015; 17: 711-717.
93 Lip GYH. et al. Relationship of the SAMe-TT2R2 score to poor-quality anticoagulation, stroke, clinically relevant bleeding, and mortality in patients with atrial fibrillation. Chest 2014; 146: 719-726.
94 Proietti M, Lip GYH.. Simple decision-making between a vitamin K antagonist and a non-vitamin K antagonist oral anticoagulant: using the SAMe-TT2R2 scor. Eur Hear J 2015; 01: 150-152.
95 Clarkesmith DE. et al. Educational intervention improves anticoagulation control in atrial fibrillation patients: the TREAT randomised trial. PLoS One 2013; 08: e74037..
96 Heidbuchel H. et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013; 15: 625-651.
97 Berti D. et al. A proposal for interdisciplinary, nurse-coordinated atrial fibrillation expert programmes as a way to structure daily practice. Eur Heart J 2013; 34: 2725-2730.
98 Hendriks JML. et al. An integrated chronic care program for patients with atrial fibrillation: study protocol and methodology for an ongoing prospective randomised controlled trial. Int J Nurs Stud 2010; 47: 1310-1316.
99 Hendriks JML. et al. Nurse-led care vs. usual care for patients with atrial fibrillation: results of a randomized trial of integrated chronic care vs. routine clinical care in ambulatory patients with atrial fibrillation. Eur Heart J 2012; 33: 2692-2699.
100 Hendriks JML. et al. The effect of a nurse-led integrated chronic care approach on quality of life in patients with atrial fibrillation. Europace 2014; 16: 491-499.
101 Stewart S. et al. Standard versus atrial fibrillation-specific management strategy (SAFETY) to reduce recurrent admission and prolong survival: pragmatic, multicentre, randomised controlled trial. Lancet 2015; 385: 775-784.
102 Demonceau J. et al. Identification and assessment of adherence-enhancing interventions in studies assessing medication adherence through electronically compiled drug dosing histories: a systematic literature review and meta-analysis. Drugs 2013; 73: 545-562.