Abstract Number: OC 71.5
Meeting: ISTH 2022 Congress
Background: A growing number of very elderly patients with non-valvular atrial fibrillation (NVAF) receive direct oral anticoagulants (DOAC) to prevent ischemic stroke and embolic events. However, no study specifically investigated xaban pharmacokinetics (PK) and pharmacodynamics (PD) in these frail polymedicated patients at high hemorrhagic and thrombotic risks.
Aims: To investigate: i/ xaban concentration-time profiles; ii/ thrombin generation (TG); and iii/ clinical outcomes 6-months after inclusion in very elderly NVAF patients receiving rivaroxaban or apixaban.
Methods: ADAGE (NCT02464488) was a prospective exploratory academic multicenter study, enrolling NVAF patients aged 80-years from geriatrics units, receiving xaban for at least 4 days. Each patient had 1-5 samples at different time-points after DOAC intake over a 20-day period. TG was investigated using ST-Genesia (Drugscreen, Thromboscreen with/without thrombomodulin). Clinical outcomes were collected at 6-months.
Results: Two-hundred-and-fifteen patients (women 71.1%, mean age 87±4-years) were included, 104-rivaroxaban and 111-apixaban, 79.5% receiving reduced-dose regimen (i.e. 15 mg qd and 2.5 mg bid, respectively). We observed important inter-individual variabilities (CV) of Cmax (47% – 45%) and Cmin (38% – 65%) in 15mg-rivaroxaban and 2.5mg-apixaban patients, respectively. Dose regimen was associated with plasma concentration and TG peak-height at Tmax (p=0.0058 and 0.0074) and Tmin (p=0.0222 and 0.0516) in apixaban samples, respectively, but not in rivaroxaban samples (multivariate analysis). Moreover, substantial variability of TG peak-height was noticed at a given plasma concentration for both xabans, suggesting the important impact on TG of the underlying coagulation status in very elderly patients. Major bleeding, thrombotic event and death rates were 6.0%, 2.3%, and 18.1%, respectively, without association with PK/PD data.
Conclusion(s): Our study provides original PK/PD data in very elderly frail patients receiving xabans in real-life setting. The potential clinical impact of such data deserves to be extensively investigated in the context of an aging world.
To cite this abstract in AMA style:FOULON-PINTO G, LAFUENTE-LAFUENTE C, JOURDI G, LE GUEN J, TALL F, PUYMIRAT E, DELRUE M, RIVIERE L, KETZ F, Gouin I, Mullier F, GAUSSEM P, PAUTAS E, LECOMPTE T, CURIS E, SIGURET V. Assessment of DOACs in GEriatrics (ADAGE) study: rivaroxaban and apixaban plasma concentrations and thrombin generation profiles in very elderly patients with non valvular atrial fibrillation [abstract]. https://abstracts.isth.org/abstract/assessment-of-doacs-in-geriatrics-adage-study-rivaroxaban-and-apixaban-plasma-concentrations-and-thrombin-generation-profiles-in-very-elderly-patients-with-non-valvular-atrial-fibrillation/. Accessed September 27, 2022.
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