PDF herunterladen
CC BY 4.0 · TH Open 2023; 07(03): e270-e279
DOI: 10.1055/a-2161-0928
Original Article

Prevalence and Predictors of Nonadherence to Direct Oral Anticoagulant Treatment in Patients with Atrial Fibrillation

Sabine F. B. van der Horst    *
1   Department of Thrombosis and Hemostasis, Leiden UMC, Leiden, The Netherlands
,
Tim A.C. de Vries    *
2   Department of Clinical and Experimental Cardiology and Cardiothoracic Surgery, Amsterdam UMC location University of Amsterdam, Heart Center, Amsterdam, The Netherlands
3   Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, Amsterdam, The Netherlands
4   Department of Cardiology, Hospital Rijnstate, Arnhem, The Netherlands
,
Gordon Chu
1   Department of Thrombosis and Hemostasis, Leiden UMC, Leiden, The Netherlands
5   Department of Internal Medicine, Alrijne Hospital, Leiden, The Netherlands
,
Roisin Bavalia
6   Department of Vascular Medicine, Amsterdam UMC location University of Amsterdam, The Netherlands
7   GGD Amsterdam, Amsterdam, The Netherlands
,
Helen Xiong
8   IQVIA Netherlands, Amsterdam, The Netherlands
,
Kayleigh M. van de Wiel
8   IQVIA Netherlands, Amsterdam, The Netherlands
,
Kelly Mulder
8   IQVIA Netherlands, Amsterdam, The Netherlands
,
Hanne van Ballegooijen
8   IQVIA Netherlands, Amsterdam, The Netherlands
,
Joris R. de Groot
2   Department of Clinical and Experimental Cardiology and Cardiothoracic Surgery, Amsterdam UMC location University of Amsterdam, Heart Center, Amsterdam, The Netherlands
3   Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, Amsterdam, The Netherlands
,
Saskia Middeldorp
9   Department of Internal Medicine, Radboudumc, Nijmegen, The Netherlands
,
Frederikus A. Klok 
1   Department of Thrombosis and Hemostasis, Leiden UMC, Leiden, The Netherlands
,
Martin E.W. Hemels
4   Department of Cardiology, Hospital Rijnstate, Arnhem, The Netherlands
10   Department of Cardiology, Radboudumc, Nijmegen, The Netherlands
,
Menno V. Huisman
1   Department of Thrombosis and Hemostasis, Leiden UMC, Leiden, The Netherlands
› Institutsangaben Funding There is no funding to report.
› Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints

Abstract

Background For most patients with newly diagnosed atrial fibrillation (AF), direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists. However, there is concern that the lack of monitoring may impair therapy adherence and therefore the anticoagulant effect.

Objective To assess 1-year DOAC nonadherence in patients with AF and a treatment indication of at least 1 year in the Dutch health care setting, and to identify predictors of nonadherence.

Methods We performed a near-nationwide historical cohort study in patients with a novel DOAC indication for AF. Data were obtained from a pharmacy database, covering 65% of all outpatient prescriptions dispensed in the Netherlands. The 1-year nonadherence was assessed by the proportion of days covered; the threshold was set at <80%. Robust Poisson regression analyses were performed to identify predictors of nonadherence.

Results A total of 46,211 patients were included and the 1-year nonadherence was 6.5%. We identified male sex (risk ratio [RR] 1.23, 95% confidence interval [CI]: 1.15–1.33), younger age (age ≥60 to <70 years: RR: 1.15, 95% CI: 1.00–1.33, age <60 years: RR: 2.22, 95% CI: 1.92–2.57; reference age ≥85 years), a reduced DOAC dose (RR: 1.10, 95% CI: 1.00–1.22), a twice-daily dosing regimen (RR: 1.21, 95% CI: 1.12–1.30), and treatment with apixaban (RR: 1.16, 95% CI: 1.06–1.26, reference rivaroxaban) or dabigatran (RR: 1.25, 95% CI: 1.14–1.37) as independent predictors of 1-year nonadherence.

Conclusion One-year nonadherence to DOACs was low yet relevant in patients with AF newly prescribed a DOAC. Understanding the predictors for nonadherence may help identify patients at risk.

Zoom Image

Keywords

direct oral anticoagulant - anticoagulants - medication adherence - atrial fibrillation

Author Contributions

All authors have contributed to the concept and design of the study. S.F.B.v.d.H., T.A.C.d.V. and G.C. conducted the analyses. S.F.B.v.d.H., T.A.C.d.V., G.C., H.X., K.M.v.d.W., H.v.B., and M.V.H. contributed to the interpretation of data. S.F.B.v.d.H. wrote the first draft of the manuscript. T.A.C.d.V., G.C., R.B., H.X., K.M.v.d.W., K.M., H.v.B., J.R.d.G., S.M., F.A.K., M.E.W.H., and M.V.H. contributed to critical revision of the manuscript for important intellectual content and gave approval of the final version to be published. M.V.H. was the study supervisor.


* Co-first authorship.


Supplementary Material



Publikationsverlauf

Eingereicht: 05. Mai 2023

Angenommen: 25. August 2023

Accepted Manuscript online:
28. August 2023

Artikel online veröffentlicht:
27. September 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 van den Heuvel JM, Hövels AM, Büller HR, Mantel-Teeuwisse AK, de Boer A, Maitland-van der Zee AH. NOACs replace VKA as preferred oral anticoagulant among new patients: a drug utilization study in 560 pharmacies in The Netherlands. Thromb J 2018; 16 (01) 7
    CrossrefPubMedGoogle Scholar
  • 2 Connolly SJ, Ezekowitz MD, Yusuf S. et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
    CrossrefPubMedGoogle Scholar
  • 3 Giugliano RP, Ruff CT, Braunwald E. et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369 (22) 2093-2104
    CrossrefPubMedGoogle Scholar
  • 4 Granger CB, Alexander JH, McMurray JJ. et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
    CrossrefPubMedGoogle Scholar
  • 5 Patel MR, Mahaffey KW, Garg J. et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
    CrossrefPubMedGoogle Scholar
  • 6 Ruff CT, Giugliano RP, Braunwald E. 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 (9921) 955-962
    CrossrefPubMedGoogle Scholar
  • 7 Ozaki AF, Choi AS, Le QT. et al. Real-world adherence and persistence to direct oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2020; 13 (03) e005969
    CrossrefPubMedGoogle Scholar
  • 8 Salmasi S, Loewen PS, Tandun R, Andrade JG, De Vera MA. Adherence to oral anticoagulants among patients with atrial fibrillation: a systematic review and meta-analysis of observational studies. BMJ Open 2020; 10 (04) e034778
    CrossrefPubMedGoogle Scholar
  • 9 Deshpande CG, Kogut S, Laforge R, Willey C. Impact of medication adherence on risk of ischemic stroke, major bleeding and deep vein thrombosis in atrial fibrillation patients using novel oral anticoagulants. Curr Med Res Opin 2018; 34 (07) 1285-1292
    CrossrefPubMedGoogle Scholar
  • 10 Desteghe L, Vijgen J, Koopman P. et al. Telemonitoring-based feedback improves adherence to non-vitamin K antagonist oral anticoagulants intake in patients with atrial fibrillation. Eur Heart J 2018; 39 (16) 1394-1403
    CrossrefPubMedGoogle Scholar
  • 11 Márquez-Contreras E, Martell-Claros N, Márquez-Rivero S. et al; Compliance and Inertia Working Group, Spanish Society of Hypertension (SEH-LELHA). Strategies for improving dabigatran adherence for stroke prevention in patients with non-valvular atrial fibrillation: education and drug intake reminders (FACILITA study). Curr Med Res Opin 2018; 34 (07) 1301-1308
    CrossrefPubMedGoogle Scholar
  • 12 Banerjee A, Benedetto V, Gichuru P. et al. Adherence and persistence to direct oral anticoagulants in atrial fibrillation: a population-based study. Heart 2020; 106 (02) 119-126
    CrossrefPubMedGoogle Scholar
  • 13 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 (08) 1150-1157
    CrossrefPubMedGoogle Scholar
  • 14 Brown JD, Shewale AR, Talbert JC. Adherence to rivaroxaban, dabigatran, and apixaban for stroke prevention for newly diagnosed and treatment-naive atrial fibrillation patients: an update using 2013-2014 data. J Manag Care Spec Pharm 2017; 23 (09) 958-967
    PubMedGoogle Scholar
  • 15 Komen JJ, Pottegård A, Mantel-Teeuwisse AK. et al. Persistence and adherence to non-vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation across five Western European countries. Europace 2021; 23 (11) 1722-1730
    CrossrefPubMedGoogle Scholar
  • 16 McHorney CA, Ashton V, Laliberté F. et al. Adherence to rivaroxaban compared with other oral anticoagulant agents among patients with nonvalvular atrial fibrillation. J Manag Care Spec Pharm 2017; 23 (09) 980-988
    PubMedGoogle Scholar
  • 17 Pham PN, Brown JD. Real-world adherence for direct oral anticoagulants in a newly diagnosed atrial fibrillation cohort: does the dosing interval matter?. BMC Cardiovasc Disord 2019; 19 (01) 64
    CrossrefPubMedGoogle Scholar
  • 18 European Pharmaceutical Market Research Assocation (EPHMRA) - Anatomical Classification of Pharmaceutical Products (ATC). Accessed November 1, 2022 at: https://www.ephmra.org/anatomical-classification
    PubMedGoogle Scholar
  • 19 ESC Guideline Novel Oral Anticoagulants for Atrial Fibrillation. European Society of Cardiology (ESC). Accessed October 17, 2022 at: https://www.escardio.org/Guidelines/Recommended-Reading/Heart-Rhythm/Novel-Oral-Anticoagulants-for-Atrial-Fibrillation
    PubMedGoogle Scholar
  • 20 Konstantinides SV, Meyer G, Becattini C. et al; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
    CrossrefPubMedGoogle Scholar
  • 21 Neumann F-J, Sousa-Uva M, Ahlsson A. et al; ESC Scientific Document Group. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J 2019; 40 (02) 87-165
    CrossrefPubMedGoogle Scholar
  • 22 Johnston R, Jones K, Manley D. Confounding and collinearity in regression analysis: a cautionary tale and an alternative procedure, illustrated by studies of British voting behaviour. Qual Quant 2018; 52 (04) 1957-1976
    CrossrefPubMedGoogle Scholar
  • 23 Jacobs MS, Schouten JF, de Boer PT, Hoffmann M, Levin LÅ, Postma MJ. Secondary adherence to non-vitamin-K antagonist oral anticoagulants in patients with atrial fibrillation in Sweden and the Netherlands. Curr Med Res Opin 2018; 34 (10) 1839-1847
    CrossrefPubMedGoogle Scholar
  • 24 Smits E, Andreotti F, Houben E. et al. Adherence and persistence with once-daily vs twice-daily direct oral anticoagulants among patients with atrial fibrillation: real-world analyses from the Netherlands, Italy and Germany. Drugs Real World Outcomes 2022; 9 (02) 199-209
    CrossrefPubMedGoogle Scholar
  • 25 Capiau A, Mehuys E, Van Tongelen I. et al. Community pharmacy-based study of adherence to non-vitamin K antagonist oral anticoagulants. Heart 2020; 106 (22) 1740-1746
    CrossrefPubMedGoogle Scholar
  • 26 Borne RT, O'Donnell C, Turakhia MP. et al. Adherence and outcomes to direct oral anticoagulants among patients with atrial fibrillation: findings from the veterans health administration. BMC Cardiovasc Disord 2017; 17 (01) 236
    CrossrefPubMedGoogle Scholar
  • 27 Giner-Soriano M, Cortes J, Gomez-Lumbreras A, Prat-Vallverdú O, Quijada-Manuitt MA, Morros R. The use and adherence of oral anticoagulants in Primary Health Care in Catalunya, Spain: a real-world data cohort study. Aten Primaria 2020; 52 (08) 529-538
    CrossrefPubMedGoogle Scholar
  • 28 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 (04) 495-504
    CrossrefPubMedGoogle Scholar
  • 29 Zielinski GD, van Rein N, Teichert M. et al. Adherence to direct oral anticoagulant treatment for atrial fibrillation in the Netherlands: a surveillance study. Pharmacoepidemiol Drug Saf 2021; 30 (08) 1027-1036
    CrossrefPubMedGoogle Scholar
  • 30 Binding C, Olesen JB, Lee CJ. et al. Discontinuation of direct oral anticoagulants among patients with atrial fibrillation according to gender and cohabitation status: a nationwide cohort study. Eur Heart J Cardiovasc Pharmacother 2022; 8 (04) 353-362
    CrossrefPubMedGoogle Scholar
  • 31 Perreault S, de Denus S, White-Guay B. et al. Oral anticoagulant prescription trends, profile use, and determinants of adherence in patients with atrial fibrillation. Pharmacotherapy 2020; 40 (01) 40-54
    CrossrefPubMedGoogle Scholar
  • 32 Dagres N, Nieuwlaat R, Vardas PE. et al. Gender-related differences in presentation, treatment, and outcome of patients with atrial fibrillation in Europe: a report from the Euro Heart Survey on Atrial Fibrillation. J Am Coll Cardiol 2007; 49 (05) 572-577
    CrossrefPubMedGoogle Scholar
  • 33 Dellafiore F, Arrigoni C, Pittella F, Conte G, Magon A, Caruso R. Paradox of self-care gender differences among Italian patients with chronic heart failure: findings from a real-world cross-sectional study. BMJ Open 2018; 8 (09) e021966
    CrossrefPubMedGoogle Scholar
  • 34 Speed V, Auyeung V, Patel JP. et al. Adherence to rivaroxaban for the treatment of venous thromboembolism-results from the FIRST registry. Res Pract Thromb Haemost 2021; 5 (08) e12614
    CrossrefPubMedGoogle Scholar
  • 35 Leslie KH, McCowan C, Pell JP. Adherence to cardiovascular medication: a review of systematic reviews. J Public Health (Oxf) 2019; 41 (01) e84-e94
    CrossrefPubMedGoogle Scholar
  • 36 Hwang J, Lee SR, Park HS. et al. Adherence to dabigatran and the influence of dabigatran-induced gastrointestinal discomfort in the real-world practice. Int J Cardiol 2021; 323: 77-82
    CrossrefPubMedGoogle Scholar
  • 37 Grymonprez M, Steurbaut S, De Sutter A, Lahousse L. Impact of a single non-sex-related stroke risk factor on atrial fibrillation and oral anticoagulant outcomes: a systematic review and meta-analysis. Open Heart 2020; 7 (02) e001465
    CrossrefPubMedGoogle Scholar
  • 38 Nau DP. Proportion of days covered (PDC) as a preferred method of measuring medication adherence. Springfield, VA. Pharmacy Quality Alliance. 2012; 6: 25
    PubMedGoogle Scholar