Edoxaban plasma levels in patients with non-valvular atrial fibrillation: Inter and intra-individual variability, correlation with coagulation screening test and renal function

Testa, Sophie; Dellanoce, Claudia; Paoletti, Oriana; Cancellieri, Emilia; Morandini, Rossella; Tala, Maurizio; Zambelli, Silvia; Legnani, Cristina

doi:10.1016/j.thromres.2019.01.008

Cited by 13 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Responses to Edx also exhibit interindividual and individual variability based on patient characteristics, which may affect patient safety. [18] In the present study, a lower preoperative CrCl was associated with an increased frequency of Edx-associated anemia. Additionally, a significant correlation was found between preoperative CrCl and PT & PT-INR during Edx treatment.…”

Section: Discussionsupporting

confidence: 54%

See 1 more Smart Citation

The importance of renal function in anemic patients treated with edoxaban after orthopedic surgery in a real-world clinical setting: A retrospective study

et al. 2022

View full text Add to dashboard Cite

Edoxaban (Edx) has been approved to prevent venous thromboembolism after total knee and/or hip arthroplasty in Japan. However, the risk of anemia with Edx treatment remains elusive. No risk factors for Edx-associated anemia after orthopedic surgery have been reported. This study aimed to clarify the risk of anemia associated with Edx treatment and determine the risk factors for Edx-associated anemia after orthopedic surgery with a high risk for bleeding. First, the association between Edx treatment and the incidence of anemia-related events was retrospectively investigated by pharmacovigilance analyses using data from 5769,866 reports between the first quarters of 2016 and 2020 in the Food and Drug Administration Adverse Event Reporting System and 2752,050 reports between the fourth quarters of 2011 and 2019 in the Japanese Adverse Drug Event Report. Second, 221 patients who underwent Edx treatment after total knee and/or hip arthroplasty between July 2011 and June 2012 at a single center were included in a case−control study to clarify the risk factors for anemia. Edx treatment was associated with an increased risk of anemia-related events in orthopedic patients. Reduced renal function was identified as a critical risk factor for Edx-associated anemia after orthopedic surgery. The present study indicates that renal function should be considered in the risk management of increased Edx-associated anemia after orthopedic surgery.

show abstract

Section: Discussionsupporting

confidence: 54%

“…Responses to Edx also exhibit interindividual and individual variability based on patient characteristics, which may affect patient safety. [ 18 ]…”

Section: Discussionmentioning

confidence: 99%

The importance of renal function in anemic patients treated with edoxaban after orthopedic surgery in a real-world clinical setting: A retrospective study

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Large pooled data analyses from phase I‐III studies did not reveal a significant relationship between apixaban exposure (TL) and clinical end‐points 25,26 . In edoxaban‐treated AF patients, TL after 24 hours and PL after 2 hours showed at least a 10‐fold inter‐individual variability 27 . The FDA data state an exposure‐response relationship for the TL in AF und VTE patients that doubling TL leads to a threefold increase in bleeding rates 28 .…”

Section: Discussionmentioning

confidence: 99%

Plasma levels do not predict thrombin generation in patients taking direct oral anticoagulants

Metze

Klöter

Stöbe

et al. 2021

Int J Lab Hematology

View full text Add to dashboard Cite

Background The antithrombotic effect of direct oral anticoagulants (DOAC) in specific clinical scenarios is difficult to assess. Objective This study aimed to evaluate the effect of DOAC on thrombin generation (TG) in relation to their plasma level. Methods Eighty patients newly started on anticoagulation were included, 20 patients for each DOAC—apixaban, edoxaban, rivaroxaban, and dabigatran. Plasma was sampled before DOAC (baseline), at plasma peak time, 6 and 12 hours after starting DOAC for quantification of drug levels and TG. Results The baseline TG before DOAC intake showed inter‐individual variability. All DOACs significantly prolonged lag time (LT) and time to peak (TTP), but did not change endogenous thrombin potential (ETP). Anti‐Xa inhibitors but not dabigatran reduced thrombin peak, but the effect of apixaban at plasma peak was less pronounced (factor 1.6). LT and TTP prolongation of dabigatran was lower compared to anti‐Xa inhibitors. All DOACs showed a nonlinear dose‐response relationship, with the greatest antithrombotic effect at lower DOAC plasma levels. The inhibition of TG parameters between baseline and peak was parallel between individual patients but the coefficient of variation of TG was lower compared to drug levels. Conclusion The antithrombotic effect at DOAC peak plasma level measured by TG depends on the patient‐specific baseline TG level and the drug‐specific inhibition by the particular DOAC. Although peak plasma levels have a high variability, the variation of TG is lower compared to drug levels. Therefore, TG assays may be superior to plasma levels in the assessment of the intensity of anticoagulation.

show abstract

“…Testa et al reported no significant correlation was found between edoxaban plasma concentrations and CrCl > 17.8 mL/min both at trough and at peak times [ 18 ]. This result seems to contradict ours, but the difference was that we separately analyzed based on the dose and Testa analyzed regardless of the dose.…”

Section: Discussionmentioning

confidence: 99%

Impact of Renal Function on Anti-factor Xa Activity Concentrations with Edoxaban Use in Patients with Non-valvular Atrial Fibrillation

et al. 2022

View full text Add to dashboard Cite

Background Chromogenic anti-factor Xa activity (AXA) assay is used to measure the pharmacodynamics of factor Xa inhibitors, including edoxaban. Although AXA concentrations in patients with non-valvular atrial fibrillation using edoxaban have been reported, the impact of renal function on AXA concentrations with edoxaban use in patients with non-valvular atrial fibrillation has not been fully assessed. Methods Trough and peak AXA concentrations were measured in 93 patients with non-valvular atrial fibrillation taking edoxaban (73.6 ± 11.2 years, 48 were male). The patients were divided into three groups: patients with moderate renal dysfunction (creatinine clearance 15-49 mL/min), mild renal dysfunction (creatinine clearance 50-95 mL/min), and normal renal function (creatinine clearance > 95 mL/min). Both trough and peak AXA concentrations were assessed among the groups according to the edoxaban dose (30 or 60 mg). Results At a 30-mg dose, patients with moderate renal dysfunction showed significantly higher trough AXA concentrations than patients with mild renal dysfunction or normal renal function. At a 60-mg dose, patients with mild renal dysfunction showed significantly higher trough AXA concentrations than patients with normal renal function. Peak AXA concentrations were not significantly different between the groups. Creatinine clearance was significantly and negatively correlated with trough AXA concentrations at a 60-mg dose, whereas the correlation of creatinine clearance with AXA concentrations was borderline significant at a 30-mg dose. No correlation was found between creatinine clearance and peak AXA concentrations at either dose. Conclusions Creatinine clearance tends to be negatively correlated with trough AXA concentrations in patients with nonvalvular atrial fibrillation taking edoxaban, while renal function is not correlated with peak AXA concentrations.

show abstract

Edoxaban plasma levels in patients with non-valvular atrial fibrillation: Inter and intra-individual variability, correlation with coagulation screening test and renal function

Cited by 13 publications

References 31 publications

The importance of renal function in anemic patients treated with edoxaban after orthopedic surgery in a real-world clinical setting: A retrospective study

The importance of renal function in anemic patients treated with edoxaban after orthopedic surgery in a real-world clinical setting: A retrospective study

Plasma levels do not predict thrombin generation in patients taking direct oral anticoagulants

Impact of Renal Function on Anti-factor Xa Activity Concentrations with Edoxaban Use in Patients with Non-valvular Atrial Fibrillation

Contact Info

Product

Resources

About