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Clinical Trial
. 2019 Jun 6;14(6):e0217302.
doi: 10.1371/journal.pone.0217302. eCollection 2019.

The daily practice of direct oral anticoagulant use in patients with atrial fibrillation; an observational cohort study

Anouk J W Gulpen  1   2   3 , Hugo Ten Cate  1   2   3 , Yvonne M C Henskens  1   2   4 , René van Oerle  1   2   4 , Rick Wetzels  4 , Simon Schalla  2   5 , Harry J Crijns  2   5 , Arina J Ten Cate-Hoek  1   2
Affiliations
Clinical Trial

The daily practice of direct oral anticoagulant use in patients with atrial fibrillation; an observational cohort study

Anouk J W Gulpen et al. PLoS One. .

Abstract

Background: Direct oral anticoagulants (DOACs) are administered in fixed doses without monitoring. There is still little published data on the impact of the absence of monitoring on adherence to medication and stability of DOAC plasma levels over time.

Objectives: To explore adherence and stability of DOAC plasma levels over time in patients with atrial fibrillation (NVAF) recently started on DOAC therapy.

Patients and methods: A prospective observational cohort study with structured follow up including assessment of adherence to medication, plasma levels at baseline, 3,6 and 12 months and adverse events.

Results: We included 164 patients; 89% were previous users of a vitamin K antagonist (VKA). One-year adherence was reasonably good: Morisky adherence measurement scores of 6-8 in 92%. The majority of DOAC plasma levels were within reported on-therapy ranges; dabigatran (median 104.4 ng/ml, IQR 110.2), rivaroxaban (median 185.2 ng/ml, IQR 216.1) and on average levels were not different for full and adjusted doses. There was significant variation between patients, but no significant differences over time within individuals. A substantial proportion of patients starting in the upper-or lower 20th percentiles remained there during the entire follow up. Seventeen bleedings (16 minor, 1 major) were reported, no ischemic events and bleeding or thrombotic events were not associated with DOAC plasma levels.

Conclusions: Adherence was reasonably good in the majority of patients. Our data confirm the stability of DOAC plasma levels over time. Knowledge of such data may, in the individual patient, contribute to optimal drug and dose selection.

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Conflict of interest statement

During the period the work was done, HTC was a consultant to the diagnostic company STAGO. However, for this specific article, this consultancy was essentially not relevant.

Figures

Fig 1
Fig 1. Trajectories for activity levels for patients on dabigatran (upper panel) and rivaroxaban (lower panel) who had one or more data points outside the 20th or 80th percentile.
The grey lines represent patients with more than one outlier; the red lines represent patients with 1 outlier.
Fig 2
Fig 2. Activity levels DOACs at different time points.
The red lines represent the calculated upper and lower 20th percentiles for the different doses. The grey shaded area represents the ‘expected on therapy’ activity levels.
Fig 3
Fig 3. Reasons used by attending physicians to adjust dabigatran dose.
See this image and copyright information in PMC

References

    1. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51. 10.1056/NEJMoa0905561 . - DOI - PubMed
    1. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91. 10.1056/NEJMoa1009638 . - DOI - PubMed
    1. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92. 10.1056/NEJMoa1107039 . - DOI - PubMed
    1. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–104. 10.1056/NEJMoa1310907 . - DOI - PubMed
    1. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893–962. 10.1093/eurheartj/ehw210 . - DOI - PubMed