OC 71.5 - 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

Wednesday, July 13, 2022

11:15 AM – 11:30 AM

Location: ExCel Center, S11B

Presentation Format: In-Person

Co-Author(s)

GF

Geoffrey FOULON-PINTO

PhD
AP-HP.Nord University of Paris
Paris, Ile-de-France, France
CL

Carmelo LAFUENTE-LAFUENTE

Associate Professor in Pharmacology
Hospital Groupe Pitié-Salpêtrière-Charles Foix/Sorbonne Paris University
Ivry-sur-Seine, Ile-de-France, France
GJ

Georges JOURDI

Post-doctoral fellow
INSERM UMR-S-1140 / University of Paris
Paris, Ile-de-France, France
JL

Julien LE GUEN

Geriatrician
Hôpital Européen Georges Pompidou/University of Paris
Paris, Ile-de-France, France
FT

Fatoumata TALL

Geriatrician
Rotschild Hospital/Sorbonne Paris University
Paris, Ile-de-France, France
EP

Etienne PUYMIRAT

Professor of Cardiology
Hôpital Européen Georges Pompidou/University of Paris
Paris, Ile-de-France, France
MD

Maxime DELRUE

Clinician
AP-HP.Nord / University of Paris
75010, Ile-de-France, France
LR

Léa RIVIERE

Resident
Hospital Group Pitié-Salpêtrière-Charles Foix/ Paris Sorbonne University
Ivry-sur-Seine, Ile-de-France, France
FK

Flora KETZ

Geriatrician
Hospital Group Pitié-Salpêtrière-Charles-Foix/Paris Sorbonne University
IIvry-sur-Seine, Ile-de-France, France
Isabelle Gouin-Thibault, Sr., PhD

Head of hemostasis department
Department of Hematology/Hemostasis, Pontchaillou University Hospital of Rennes, Univ Rennes, Irset - Inserm UMR_S 1085, Rennes, France.
Rennes, Bretagne, France
FM

François Mullier

Professor
University Hospital of Namur
Namur, Namur, Belgium
PG

Pascale Gaussem

Professor
Université Paris Cité, INSERM U1140, Innovative Therapies in Haemostasis, France
Paris, Ile-de-France, France
EP

Eric PAUTAS

Professor in Geriatrics
Hospital Group Pitié-Salpêtrière-Charles Foix - Paris Sorbonne University
Ivry-sur-Seine, Ile-de-France, France
TL

Thomas Lecompte

Professor
Université de Lorraine, Nancy, France
Nancy, Lorraine, France
EC

Emmanuel CURIS

Biostatistician
Faculty of Pharmacy / University of Paris
Paris, Ile-de-France, France

Presenting Author(s)

VS

Virginie Siguret, PhD, PharmD

PharmD PhD, Professor in Hematology
INSERM UMR-S-1140, Innovative therapies in Haemostasis, Université Paris Cité, Paris
Paris, Ile-de-France, France

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.