Medication adherence to non-vitamin K antagonist oral anticoagulants at non-valvular atrial fibrillation – the literature review

Authors: Simona Dvořáčková 1;  Kateřina Ládová 1,2;  Josef Malý 1,3;  Jozef Kolář 1;  Miroslav Penka 4
Authors‘ workplace: Katedra sociální a klinické farmacie Farmaceutické fakulty UK v Hradci Králové 1;  Oddělení klinické farmacie Nemocnice Na Homolce, Praha 2;  Oddělení klinické farmacie Nemocniční lékárny FN v Motole, Praha 3;  Oddělení klinické hematologie FN Brno 4
Published in: Vnitř Lék 2017; 63(10): 633-639
Category: Original Contributions


Medication adherence is a complex problem reflecting variations in terms of medication taking behavior. It is essential in maximizing of the effect and risk minimization of the therapy and health care costs reduction, even in the case of oral anticoagulants (non-vitamin K antagonist oral anticoagulants – NOACs). The aim of this paper was to review the published literature and to discuss results in the field of medication adherence to NOACs in patients with non-valvular atrial fibrillation (NVAF). Based on the searching in databases Embase and PubMed 25 studies were identified, of which conclusions were summarized in this paper. Patients treated with dabigatran reported poorer medication adherence than patients with rivaroxaban. However, medication adherence is influenced by many circumstances as well as included studies were not sufficiently uniform, therefore, a prerequisite for further investigation of this issue is expected.

Key words:
apixaban – atrial fibrillation – dabigatran – medication adherence – patient compliance – rivaroxaban


1. Kehinde OO, Chalmers L, Bereznicki LR. A Summary of the Literature Evaluating Adherence and Persistence with Oral Anticoagulants in Atrial Fibrilation. Am J Cardiovasc Drugs 2016; 16(5): 349–363. Dostupné z DOI: <–016–0171–6>.

2. 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(4): 514–523. Dostupné z DOI: <>.

3. Vrijens B, De Geest S, Hughes K et al. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol 2012; 73(5): 691–705. Dostupné z DOI: <–2125.2012.04167.x>.

4. Wilke T, Bauer S, Mueller S et al. Patient Preferences for Oral Anticoagulation Therapy in Atrial Fibrillation: A Systematic Literature Review. Patient 2017; 10(1): 17–37. Dostupné z DOI: <–016–0185–9>.

5. Sabaté E. Adherence to long-term therapies. Evidence for action. WHO Library Cataloguing-in-Publication Data: Geneva2003: 3–6. ISBN 92 4 154599 2. Dostupné z DOI: <>.

6. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353(5): 487–497.

7. Michalcová J, Penka M, Bulíková A et al. Nová – přímá perorální antikoagulancia: aktuální přehled. Vnitř Lék 2016; 62(10): 805–813.

8. Kvasnička J, Penka M, Kvasnička T et al. Doporučení České společnosti pro trombózu a hemostázu České lékařské společnosti J. E. Purkyně pro bezpečnou léčbu novými perorálními antikoagulancii (NOAC) – dabigatran etexilátem, apixabanem a rivaroxabanem. Vnitř Lék 2015; 61(6): 537–546.

9. Heidbuchel H, Verhamme P, Alings M 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; 17(10): 1467–1507. Dostupné z DOI: <>.

10. Kirchhof P, Benussi S, Kotecha D et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37(38): 2893–2962.

11. Ladova K, Vytrisalova M, Vlcek J. Measures of adherence to therapy in patients with osteoporosis. Osteol Bull 2013; 18(1): 15–20.

12. Lehmann A, Aslani P, Ahmed R et al. Assessing medication adherence: options to consider. Int J Clin Pharm 2014; 36(1): 55–69. Dostupné z DOI: <–013–9865-x>.

13. Verdecchia P, Molini G, Bartolini C et al. Safety of dabigatran in an elderly population: Single center experience in Italy. Curr Drug Saf 2015; 10(2): 165–169.

14. Schulman S, Shortt B, Robinson M et al. Adherence to anticoagulant treatment with dabigatran in a real-world setting. J Thromb Haemost 2013; 11(7): 1295–1299. Dostupné z DOI: <>.

15. Marquez-Contreras E, Martell-Carlos N, Gil-Guillen V et al. Therapeutic compliance with rivaroxaban in preventing stroke in patients with non-valvular atrial fibrillation: CUMRIVAFA study. Curr Med Res Opin 2016; 32(12): 2013–2020.

16. Farmer KC. Methods for measuring and monitoring medication regimen adherence in clinical trials and clinical practice. Clin Ther 1999; 21(6): 1074–1090.

17. De Bleser L, De Geest S, Vandenbroeck S et al. How accurate are electronic monitoring devices? A laboratory study testing two devices to measure medication adherence. Sensors (Basel) 2010; 10(3): 1652–1660. Dostupné z DOI: <>.

18. Choi JC, Dibonaventura MD, Kopenhafer L et al. Survey of the use of warfarin and the newer anticoagulant dabigatran in patients with atrial fibrillation. Patient Prefer Adherence 2014; 8: 167–177. Dostupné z DOI: <>.

19. Andrade JG, Krahn AD, Skanes AC et al. Values and Preferences of Physicians and Patients With Nonvalvular Atrial Fibrillation Who Receive Oral Anticoagulation Therapy for Stroke Prevention. Can J Cardiol 2016; 32(6): 747–753. Dostupné z DOI: <>.

20. Castellucci LA, Shaw J, Van Der Salm K et al. Self-reported adherence to anticoagulation and its determinants using the Morisky medication adherence scale. Thromb Res 2015; 136(4): 727–731. Dostupné z DOI: <>.

21. Luger S, Hohmann C, Niemann D et al. Adherence to oral anticoagulant therapy in secondary stroke prevention – impact of the novel oral anticoagulants. Patient Prefer Adherence 2015; 9: 1695–1705. Dostupné z DOI: <>.

22. Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care 1986; 24(1): 67–74.

23. Knobela H, Alonsob J, Casadoc JL et al. Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study. AIDS 2002; 16(4): 605–613.

24. Ortega Suárez FJ, Sánchez Plumed J, Pérez Valentín MA et al. Validation on the simplified medication adherence questionnaire (SMAQ) in renal transplant patients on tacrolimus. Nefrologia 2011; 31(6): 690–696. Dostupné z DOI: <>.

25. Hu YF, Liao JN, Chern CM et al. Identification and management of noncompliance in atrial fibrillation patients receiving dabigatran: the role of a drug monitor. Pacing Clin Electrophysiol 2015; 38(4): 465–471. Dostupné z DOI: <>.

26. Beyer-Westendorf J, Ehlken B, Evers T. Real-world persistence and adherence to oral anticoagulation for stroke risk reduction in patients with atrial fibrillation. Europace 2016; 18(8): 1150–1557. Dostupné z DOI: <>.

27. Forslund T, Wettermark B, Hjemdahl P. Comparison of treatment persistence with different oral anticoagulants in patients with atrial fibrillation. Eur J Clin. Pharmacol 2016; 72(3): 329–338. Dostupné z DOI: <–015–1983-z>.

28. Alberts MJ, Peacock WF, Fields LE 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. Dostupné z DOI: <>.

29. Brown JD, Shewale AR, Talbert JC. Adherence to Rivaroxaban, Dabigatran, and Apixaban for Stroke Prevention in Incident, Treatment-Naïve Nonvalvular Atrial Fibrillation. J Manag Care Spec Pharm 2016; 22(11): 1319–1329.

30. Yao X, Abraham NS, Alexander GC 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; 5(2). pii: e003074. Dostupné z DOI: <>.

31. Lee PY, Han SY, Miyahara RK. Adherence and outcomes of patients treated with dabigatran: pharmacist-managed anticoagulation clinic versus usual care. Am J Health Syst Pharm 2013; 70(13): 1154–1161. Dostupné z DOI: <>.

32. Shore S, Ho PM, Lambert-Kerzner A et al. Site-level variation in and practices associated with dabigatran adherence. JAMA 2015; 313(14): 1443–1450. Dostupné z DOI: <>.

33. Michel J, Mundell D, Boga T et al. Dabigatran for anticoagulation in atrial fibrillation – early clinical experience in a hospital population and comparison to trial data. Heart Lung Circ 2013; 22(1): 50–55. Dostupné z DOI: <>.

34. Hanon O, Chaussade E, Gueranger P et al. Patient-Reported Treatment Satisfaction with Rivaroxaban for Stroke Prevention in Atrial Fibrillation. A French Observational Study, the SAFARI Study. PLoS One 2016; 11(12): e0166218. Dostupné z DOI: <>.

35. Polymeris AA, Traenka C, Hert L et al. Frequency and Determinants of Adherence to Oral Anticoagulants in Stroke Patients with Atrial Fibrillation in Clinical Practice. Eur Neurol 2016; 76(3–4): 187–193.

36. SPC Pradaxa. Dostupné z WWW: <>.

37. Zhou M, Chang HY, Segal JB et al. Adherence to a novel oral anticoagulant among patients with atrial fibrillation. J Manag Care Spec Pharm 2015; 21(11): 1054–1062.

38. Shore S, Carey EP, Turakhia MP et al. Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the veterans health administration. Am Heart J 2014; 167(6): 810–817. Dostupné z DOI: <>.

39. Gorst-Rasmussen A, Skjoth F, Larsen TB et al. Dabigatran adherence in atrial fibrillation patients during the first year after diagnosis: a nationwide cohort study. J Thromb Haemost 2015; 13(4): 495–504. Dostupné z DOI: <>.

40. Kilickiran Avci B, Vatan B, Ozden Tok O et al. The Trends in Utilizing Nonvitamin K Antagonist Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation: A Real-Life Experience. Clin Appl Thromb Hemost 2016; 22(8): 785–791.

41. McHorney CA, Peterson ED, Laliberte F et al. Comparison of Adherence to Rivaroxaban Versus Apixaban Among Patients With Atrial Fibrillation. Clin Ther 2016; 38(11): 2477–2488. Dostupné z DOI: <>.

42. Al-Khalili F, Lindstrom C, Benson L. Adherence to anticoagulant treatment with apixaban and rivaroxaban in a real-world setting. Clin Trials Regul Sci Cardiol 2016; 18: 1–4. Dostupné z DOI: <>.

43. Ho JC, Chang AM, Yan BP et al. Dabigatran compared with warfarin for stroke prevention with atrial fibrillation: experience in Hong Kong. Clin Cardiol 2012; 35(12): E40-E45. Dostupné z DOI: <>.

44. Huisman MV, Lip GYH, Diener HC et al. Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: Resolving uncertainties in routine practice. Thromb Haemost 2012; 107(5): 838–847. Dostupné z DOI: <–10–0718>.

45. Agewall S, Cattaneo M, Collet JP et al. Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy. Eur Heart J 2013; 34(23): 1708–1713. Dostupné z DOI: <>.

46. Tsivgoulis G, Krogias C, Sands KA et al. Dabigatran etexilate for secondary stroke prevention: the first year experience from a multicenter short-term registry. Ther Adv Neurol Disord 2014; 7(3): 155–161. Dostupné z DOI: <>.

Diabetology Endocrinology Internal medicine

Article was published in

Internal Medicine

Issue 10

2017 Issue 10

Most read in this issue

This topic is also in:

Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account