Abstract: TH-PO1116
Exploring the Pharmacokinetics, Pharmacodynamics, and Safety of Apixaban in Hemodiafiltration: Insights from the HEMOCIONA Study
Session Information
- Late-Breaking Posters
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Hueso, Miguel, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalunya, Spain
- Otero, Aurema, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalunya, Spain
- Rosselló-Palmer, Elena, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalunya, Spain
- Peris Vidal, Juan, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalunya, Spain
- Codina Sanchez, Sergi, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalunya, Spain
- Martínez Vilar, Yurema, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalunya, Spain
- Rigo-Bonnin, Raúl, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalunya, Spain
- Lloberas, Nuria, Institut d'Investigacio Biomedica de Bellvitge, Barcelona, Catalunya, Spain
- Videla Cés, Sebastián, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalunya, Spain
Group or Team Name
- HEMOCIONA
Background
Atrial fibrillation (AF) is common among hemodialysis (HD) patients, and increases the risk of stroke. Since vitamin K antagonists increase the risk of bleeding and vascular calcifications, direct oral anticoagulants (DOACs) has attracted considerable attention. However, there is limited experience with DOACs in HD patients and concerns have been raised about their potential accumulation. Consequently, DOACs are currently not recommended in HD patients.
Our study aims to assess the safety of low-dose of apixaban, based on long-term their pharmacokinetic profile, for patients with nonvalvular AF undergoing hemodiafiltration.
Methods
We conducted a single-center phase 2 clinical trial to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of apixaban at a dose of 2.5 mg twice daily (BID) over a period of 4 weeks. Plasma levels were obtained during the middle dialysis session of the week, as well as the day before and after for PK/PD assessments. Concentration of apixaban was directly measured in plasma, urine and dialysis wasted liquid using a validated liquid chromatography-mass spectrometry/mass spectrometry LC-MS/MS). Blood samples for the determination of Anti-FXa activity A (AXA) were collected at the same time points as the PK samples.
Results
A total of 11 patients (8 male, 3 female) with a mean age of 67±3 years old were enrolled. The main result was the demonstration of the absence of accumulation of apixaban since daily exposure (mean (%CV) AUC0-12) appeared similar the day of dialysis of the first week (1030 (0.51) mcg*h/mL), and after 4 weeks (921 (0.42) mcg*h/mL). Hemodiafiltration had no impact on apixaban plasma concentration and patients without residual diuresis did not show higher apixaban levels. A close temporal relationship between apixaban plasma concentrations and AXA was observed across the dosing intervals. No bleeding events were observed.
Conclusion
Our results have significant clinical implications, as they provide PK/PD data that justify the use of 2.5 mg BID in patients with atrial fibrillation on hemodiafiltration. Our findings emphasize the importance of considering intersubject variability in drug response and adopting individualized treatment approaches.
Funding
- Government Support - Non-U.S.