Determinants of label non-adherence to non-vitamin K oral anticoagulants in patients with newly diagnosed atrial fibrillation

Abstract

Aims To evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients. Methods and results In the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01–1.02], lower renal function (OR: 0.96 per ml/min/1.73 m2, 0.92–0.98), lower weight (OR: 0.98 per kg, 0.97–1.00), active malignancy (OR: 2.46, 1.19–5.09), anaemia (OR: 1.73, 1.08–2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57–9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88–0.96) and lower renal function (OR: 0.98 per ml/min/1.73 m2, 0.96–1.00). Conclusion In newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets.

Clinical characteristics of apixaban prescription in AF patients with single dose-reduction criterion: the ASPIRE (efficAcy and safety of aPixaban in rEal-world practice in Korean frail patients with atrial fibrillation) study

“…In those with a body weight of ≤60 kg, concomitant APT was significantly associated with reduced dose. These factors overlapped with previously reported factors associated with off-label reduced dose ( 33 – 35 ). Therefore, physicians are likely to adopt a lower dose of apixaban for patients with a marginal value of additional dose reduction criteria or other factors that represent frailty.…”

“…In previous studies, factors such as age, renal dysfunction, past medical history (prior bleeding, hypertension, and congestive heart failure), anaemia, and concomitant APT were found to affect the physicians' prescription of a reduced dose of DOACs ( 33 – 35 ). In our study, the off-label reduced dose group had more comorbidities, such as hypertension, heart failure, and a history of bleeding, suggesting that physicians might be prescribing reduced doses to mitigate bleeding risks.…”

Appropriateness of antithrombotics in geriatric inpatients with atrial fibrillation: a retrospective, cross-sectional study

“…While a presumed increased bleeding risk might push prescribers towards using lower DOAC doses, we could not retain a positive bleeding history as a determinant for underdosing. Moreover, we did not find any association between underdosing and other typical determinants such as age, number of comorbidities, renal function or even recurrent falling 21 22. Only the year 2022 showed a significant association (OR 0.104; 95% CI, 0.012–0.878), during which underdosing was less common.…”

“…Uni- and multi-variable logistic regression models were built to identify determinants for the most common cause of inappropriateness. We included the following determinants: advanced age (>85 years), BMI, creatine clearance (CrCl), history of bleeding and thromboembolic events, history of recent recurrent falling, number of CCI comorbidities, presence of anaemia, CHA 2 DS 2 -VASc score, HAS-BLED score, and calendar year (2020, 2021, 2022) 21 22. The Chi-squared test was used to evaluate the association of time (year) with appropriateness of antithrombotic therapy (appropriate vs inappropriate).…”

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“…In previous studies, factors such as age, renal dysfunction, past medical history (prior bleeding, hypertension, and congestive heart failure), anaemia, and concomitant APT were found to affect the physicians' prescription of a reduced dose of DOACs (33)(34)(35). In our study, the off-label reduced dose group had more comorbidities, such as hypertension, heart failure, and a history of bleeding, suggesting that physicians might be prescribing reduced doses to mitigate bleeding risks.…”