Assessment of DOAC in GEriatrics (ADAGE study): rivaroxaban/apixaban concentrations and thrombin generation profiles in NVAF very elderly patients.

Foulon-Pinto, Geoffrey;Lafuente, Carmelo;Jourdi, Georges;Le Guen, Julien;Siguret, Virginie;et.al.
(2023) Thrombosis and Haemostasis : international journal for vascular biology and medicine — Vol. 123, n° 4, p. 402-414 (2023)

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Authors
  • Foulon-Pinto, Geoffrey
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  • Lafuente, Carmelo
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  • Jourdi, Georges
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  • Le Guen, Julien
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  • Mullier, Françoisorcid-logoUCLouvain
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  • Siguret, Virginieorcid-logo
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Abstract
Although a growing number of very elderly patients with atrial fibrillation (AF), multiple conditions and polypharmacy, receive direct oral anticoagulants (DOAC), few studies specifically investigated both apixaban/rivaroxaban pharmacokinetics and pharmacodynamics in such patients. To investigate: i/DOAC concentration-time profiles; ii/thrombin generation (TG); and iii/clinical outcomes 6-months after inclusion in very elderly AF in-patients receiving rivaroxaban or apixaban. ADAGE-NCT02464488 was an academic prospective exploratory multicenter study, enrolling AF in-patients aged 80-years, receiving DOAC for at least 4 days. Each patient had 1-5 blood samples at different time-points over 20-days. DOAC concentrations were determined using chromogenic assays. TG was investigated using ST-Genesia (STG-ThromboScreen, STG-DrugScreen). We included 215 patients (women 71.1%, mean age 87±4-years), 104-rivaroxaban and 111-apixaban, 79.5% receiving reduced-dose regimen. We observed important inter-individual variabilities (CV) whatever the regimen, at Cmax [49-46%] and Cmin [75-61%] in 15mg-rivaroxaban and 2.5mg-apixaban patients, respectively. Dose regimen was associated with Cmax and Cmin plasma concentrations in apixaban (p=0.0058 and p=0.0222, respectively), but not in rivaroxaban samples (multivariate analysis). Moreover, substantial variability of thrombin peak-height (STG-Thromboscreen) was noticed at a given plasma concentration for both xabans, suggesting an impact of the underlying coagulation status on TG in elderly in-patients. After 6-month follow-up, major bleeding/thrombo-embolic event/death rates were 6.7%/1.0%/17.3% in rivaroxaban and 5.4%/3.6%/18.9% in apixaban patients, respectively. Our study provides original data in very elderly patients receiving DOAC in real-life setting, showing great inter-individual variability in plasma concentrations and TG parameters. Further research is needed to understand the potential clinical impact of these findings.
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Foulon-Pinto, G., Lafuente, C., Jourdi, G., Le Guen, J., Tall, F., Puymirat, E., Delrue, M., Riviere, L., Ketz, F., Gouin-Thibault, I., Mullier, F., Gaussem, P., Pautas, E., Lecompte, T., Curis, E., & Siguret, V. (2023). Assessment of DOAC in GEriatrics (ADAGE study): rivaroxaban/apixaban concentrations and thrombin generation profiles in NVAF very elderly patients. Thrombosis and Haemostasis : international journal for vascular biology and medicine, 123(4), 402-414. https://doi.org/10.1055/a-1981-1763 (Original work published 2023)