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Apixaban drug level monitoring in hemodialysis

Schietzel, S.; Limacher, A.; Moor, M. B.; Czerlau, C.; Vogt, B.; Aregger, F.; Uehlinger, D. E.

2023-06-20 nephrology
10.1101/2023.06.13.23291319 medRxiv
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BackgroundApixaban is increasingly being used in hemodialysis patients. However, uncertainty remains regarding appropriate dosing and risk of accumulation. MethodsWe analyzed apixaban drug levels from a tertiary care dialysis unit collected between August 2017 and January 2023. We compared 2.5 mg once versus twice daily dosing. We applied mixed-effects models analyses including dialysis modality, adjusted standard Kt/V, ultrafiltration and dialyzer characteristics. ResultsWe analyzed 143 apixaban drug levels from 24 patients. Mean (SD) age was 64.2 (15.3) years (45.2% female), median (IQR) follow up 12.5 (5.5 - 21) months. For the 2.5 mg once and twice daily groups, median (IQR) drug levels were 54.4 (< 40 - 72.1) and 71.3 (48.8 - 104.1) ng/mL (P < 0.001). Drug levels were below the detection limit in 30 % and 14 %. Only dosing group (twice versus once daily) was independently associated with higher drug levels (P = 0.002). Follow-up did not suggest accumulation. 95th percentile did not exceed those of non-CKD populations taking 5 mg twice daily. Drug levels before a bleeding (8 episodes) were significantly higher than those without a subsequent bleeding: 115 (SD 51.6) versus 65.9 (SD 31.6) ng/mL (P < 0.001). Patients with versus without a bleeding took concomitant antiplatelet therapy in 86% versus 6% (P < 0.001). In 21% of patients, drug level monitoring resulted in change of dosing. ConclusionApixaban drug monitoring might be a contributory tool to increase safety in patients on hemodialysis. Further prospective outcome studies are warranted to investigate possible target levels.

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