Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Edoxaban Exposure in Patients With Atrial Fibrillation and Estimated Creatinine Clearance Exceeding 100 mL/min.

ABSTRACT: Edoxaban 60 mg is approved for stroke prevention in patients with atrial fibrillation (AF) not fulfilling any dose-reduction criteria. As edoxaban is partially renally cleared (≈50%), this study compared pharmacokinetics (PK) and pharmacodynamics of edoxaban 60 mg once daily with edoxaban 75 mg once daily in patients with AF with high renal clearance (creatinine clearance > 100 mL/min) over 12 months. Primary PK and pharmacodynamics end points were plasma edoxaban exposure and anti-factor Xa (FXa) concentration. A population PK model estimated edoxaban exposure at steady state. Efficacy and safety outcomes included composites of stroke, transient ischemic attack, systemic embolism, and major and clinically relevant nonmajor bleeding. Of 607 patients, 303 and 304 were randomized to edoxaban 60 and 75 mg, respectively. Edoxaban 75 mg provided ≈25% higher exposure than 60 mg. This increase was accurately depicted in the population PK model; anti-factor Xa concentration correlated with edoxaban exposure. Rates of composite and individual outcomes were similarly low between doses. In conclusion, the 25% increase in edoxaban dose (60-75 mg) resulted in ≈25% exposure increase in the 75-mg group. Higher exposure was not associated with reduced stroke risk in patients with AF with high renal clearance.

SUBMITTER: Yin O

PROVIDER: S-EPMC9299591 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Edoxaban in patients with atrial fibrillation.

Project description:Edoxaban, a direct factor Xa inhibitor, was extensively studied in the prevention and treatment of venous thromboembolism and in patients with nonvalvular atrial fibrillation (AF). The aim of this review is to focus specifically on the efficacy and safety profile of edoxaban in patients with AF from preclinical development through the phase III trial that led to regulatory approval.

| S-EPMC5942795 | biostudies-literature

Predictive ability of creatinine clearance versus estimated glomerular filtration rate for outcomes in patients with non-valvular atrial fibrillation: Subanalysis of the J-RHYTHM Registry.

Project description:BackgroundRenal impairment is a risk factor for various adverse events, especially for death. In general, creatinine clearance (CrCl) is used for dose-adjustments of many drugs including oral anticoagulants, and estimated glomerular filtration rate (eGFR) is adopted for the diagnosis of chronic kidney disease. Predictive ability of CrCl versus eGFR for outcomes in patients with non-valvular atrial fibrillation (NVAF) remains controversial; therefore, this was compared using data from the J-RHYTHM Registry.MethodsOut of 7406 outpatients with NVAF from 158 institutions, 6004 (age, 69.7 ± 9.9 years; men, 71.2%) having data of CrCl (mL/min, by the Cockcroft-Gault formula), eGFR (mL/min/1.73 m2, by the equations of the Japanese Society of Nephrology), and body surface area (BSA) were analyzed. C-statistics (area under the receiver-operating characteristic curve) of CrCl and eGFR for events were compared by DeLong's test.ResultsThromboembolism, major hemorrhage, and all-cause death occurred in 107 (1.8%), 117 (1.9%), and 154 (2.6%) patients during the 2-year follow-up period. C-statistics of CrCl for each event were 0.609 (95% confidence interval, 0.559-0.658), 0.599 (0.548-0.657), and 0.746 (0.706-0.786); and those of eGFR were 0.542 (0.487-0.597), 0.573 (0.519-0.626), and 0.677 (0.631-0.723), respectively. C-statistics of CrCl for thromboembolism and all-cause death were significantly higher than those of eGFR (P < 0.001 for both). These results were consistent when BSA-unadjusted eGFR was used instead of eGFR (P = 0.002 for thromboembolism and P < 0.001 for all-cause death).ConclusionsCrCl was superior to eGFR in the prediction of adverse outcomes, i.e., thromboembolism and all-cause death in Japanese patients with NVAF.

| S-EPMC7298529 | biostudies-literature

Changes over time in creatinine clearance and comparison of emergent adverse events for HIV-positive adults receiving standard doses (300 mg/day) of lamivudine-containing antiretroviral therapy with baseline creatinine clearance of 30-49 vs ?50 mL/min.

Project description:A retrospective analysis of the randomized controlled DART (Development of AntiRetroviral Therapy in Africa; ISRCTN13968779) trial in HIV-1-positive adults initiating antiretroviral therapy with co-formulated zidovudine/lamivudine plus either tenofovir, abacavir, or nevirapine was conducted to evaluate the safety of initiating standard lamivudine dosing in patients with impaired creatinine clearance (CLcr). Safety data collected through 96 weeks were analyzed after stratification by baseline CLcr (estimated using Cockcroft-Gault) of 30-49 mL/min (n = 168) versus ?50 mL/min (n = 3,132) and treatment regimen. The Grade 3-4 adverse events (AEs) and serious AEs (for hematological, hepatic and gastrointestinal events), maximal toxicities for liver enzymes, serum creatinine and bilirubin and maximum treatment-emergent hematology toxicities were comparable for groups with baseline CLcr 30-49 versus CLcr?50 mL/min. No new risks or trends were identified from this dataset. Substantial and similar increases in the mean creatinine clearance (>25 mL/min) were observed from baseline though Week 96 among participants who entered the trial with CLcr 30-49 mL/min, while no increase or smaller median changes in creatinine clearance (<7 mL/min) were observed for participants who entered the trial with CLcr ?50 mL/min. Substantial increases (> 150 cells/ mm3) in mean CD4+ cells counts from baseline to Week 96 were also observed for participants who entered the trial with CLcr 30-49 mL/min and those with baseline CLcr ?50 mL/min. Though these results are descriptive, they suggest that HIV-positive patients with CLcr of 30-49 mL/min would have similar AE risks in comparison to patients with CLcr ?50 mL/min when initiating antiretroviral therapy delivering doses of 300 mg of lamivudine daily through 96 weeks of treatment. Overall improvements in CLcr were observed for patients with baseline CLcr 30-49 mL/min.

| S-EPMC6855468 | biostudies-literature

Factors Associated With Edoxaban Concentration Among Patients With Atrial Fibrillation.

Project description:Background and Purpose: Edoxaban exposure varies across different ethnicities. The purpose of our study was to examine the risk factors associated with high or low edoxaban concentrations in Asian populations. Methods: Participants with atrial fibrillation who were undergoing edoxaban therapy were enrolled. Peak (1-4 h after edoxaban administration) and trough (24 ± 4 h from the last edoxaban dose) blood samples were collected to measure edoxaban concentrations using ultrahigh-performance liquid chromatography with tandem mass spectrometry. The edoxaban concentrations were compared to those observed in clinical trials to define a higher- or lower-than-expected range. Multivariate logistic regression was used to analyze the risk factors associated with high or low edoxaban concentrations. Results: Eighty participants (49 men, 61.3%) were enrolled and provided 78 trough and 76 peak samples. Twenty participants (25.6%) were determined to have low trough concentrations, which was associated with higher creatinine clearance and the use of the 30 mg regimen (odds ratio [OR] and 95% confidence interval [CI], 1.06 [1.01, 1.11], p = 0.01 and 5.77 [1.34, 24.75], p = 0.02, respectively). In contrast, 21 participants (27.6%) had high peak concentrations, which was associated with an off-label overdosing regimen (OR = 4.68 [1.23, 17.70], p = 0.02). Conclusion: Our study identified factors associated with increased or decreased edoxaban exposure. The measurement of edoxaban concentration may be recommended for patients with selected characteristics.

| S-EPMC8458830 | biostudies-literature

Clinical Evidence for the Choice of the Direct Oral Anticoagulant in Patients with Atrial Fibrillation According to Creatinine Clearance.

Project description:Atrial fibrillation (AF) often coexists with chronic kidney disease (CKD), which confer to the patient a higher risk of both thromboembolic and hemorrhagic events. Oral anticoagulation therapy, nowadays preferably with direct oral anticoagulants (DOACs), represents the cornerstone for ischemic stroke prevention in high-risk patients. However, all four available DOACs (dabigatran, apixaban, rivaroxaban and edoxaban) are eliminated by the kidneys to some extent. Reduced kidney function facilitates DOACs accumulation and, therefore, different dose reductions are required, with slight differences between American and European recommendations especially in case of severe renal impairment (creatinine clearance < 30 mL/min). Overall, the use of DOACs in patients with non-end stage CKD and AF is effective similarly to warfarin, showing a better safety profile. The management of thromboembolic risk among patients with AF on dialysis remains challenging, as warfarin effectiveness for stroke prevention in this population is questionable and retrospective data on apixaban need to be confirmed on a larger scale. In kidney transplant recipients, DOACs may provide a potentially safer option compared to warfarin, but co-administration with immunosuppressants is a matter of concern.

| S-EPMC8003529 | biostudies-literature

Impact of creatinine clearance on outcomes in patients with non-valvular atrial fibrillation: a subanalysis of the J-RHYTHM Registry.

Project description:AimsTo clarify the influence of renal function on adverse outcomes in patients with non-valvular atrial fibrillation (NVAF), a post hoc analysis of the J-RHYTHM Registry was performed.Methods and resultsA consecutive series of outpatients with atrial fibrillation (AF) were enrolled from 158 institutions and followed for 2 years or until the occurrence of an event. Among 7406 patients with non-valvular AF, 6052 patients (69.8 ± 10.0 years, 71.2% men) with creatinine clearance (CrCl) value at baseline were divided into four groups according to CrCl level (<30, 30-49.9, 50-79.9, and ≥80 mL/min). Patients with CrCl <80 mL/min showed increased incidence of thromboembolism, major haemorrhage, all-cause and cardiovascular death, and composite events as compared with patients with CrCl ≥80 mL/min. After adjustment for multiple confounders, lower CrCl values emerged as independent predictors for thromboembolism [CrCl 30-49.9, hazard ratio (HR) 2.27, 95% confidence interval (CI) 1.09-4.72, P = 0.029; and CrCl 50-79.9, HR 1.99, 95% CI 1.07-3.72, P = 0.030] and all-cause death (CrCl <30, HR 6.44, 95% CI 3.03-13.7, P < 0.001; and CrCl 30-49.9, HR 3.14, 95% CI 1.54-6.41, P = 0.002), with CrCl ≥80 mL/min serving as a reference, whereas not for major haemorrhage. Warfarin treatment was associated with lower rates of composite events in patients with lower CrCl values of <80 mL/min.ConclusionRenal impairment was an independent predictor of adverse clinical outcomes except for major haemorrhage in Japanese patients with non-valvular AF. Warfarin was associated with lower rates of composite events in patients with lower CrCl values.Clinical trial registrationhttp://www.umin.ac.jp/ctr/. Unique identifier: UMIN000001569.

| S-EPMC5862022 | biostudies-literature

Remdesivir in Patients With Estimated GFR <30 ml/min per 1.73 m<sup>2</sup> or on Renal Replacement Therapy.

Project description: Not available

| S-EPMC7694470 | biostudies-literature

Comparison of Once-Daily Administration of Edoxaban and Rivaroxaban in Asian Patients with Atrial Fibrillation.

Project description:It is unclear whether the two once-daily dosing non-vitamin K antagonist oral anticoagulants (NOACs), edoxaban and rivaroxaban, have similar effectiveness and safety in Asian patients with non-valvular atrial fibrillation (AF). This study aimed to compare the effectiveness and safety of edoxaban and rivaroxaban in a Korean population with non-valvular AF. Using the Korean National Health Insurance Service database from January 2014 to December 2016, we compared the risk of ischemic stroke, intracranial hemorrhage (ICH), hospitalization for gastrointestinal (GI) bleeding, hospitalization for major bleeding, all-cause death, and composite outcome in a 3:1 propensity score matched cohort in patients with AF who were naïve to rivaroxaban (n = 12,369) and edoxaban (n = 4,123). Hazard ratios for the six clinical outcomes were analyzed using Cox regression analysis with rivaroxaban as the reference. Baseline characteristics were balanced between the two groups (median age, 71 years; median CHA2DS2-VASc score, 3; 56% of patients received a reduced dose). Edoxaban users showed comparable results in all six clinical outcomes (all p = nonsignificant) when compared to rivaroxaban users for total, standard, and reduced doses. We provide for the first time the comparison of effectiveness and safety between the two once-daily NOACs in a large-scale Asian AF population. In both standard and reduced dose regimens, edoxaban showed comparable effectiveness and safety compared to rivaroxaban.

| S-EPMC6491445 | biostudies-literature

Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial.

Project description:AimsEdoxaban is a direct factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF). Uninterrupted edoxaban therapy in patients undergoing AF ablation has not been tested.Methods and resultsThe ELIMINATE-AF trial, a multinational, multicentre, randomized, open-label, parallel-group study, was conducted to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for dose reduction) vs. vitamin K antagonists (VKAs) in AF patients undergoing catheter ablation. Patients were randomized 2:1 to edoxaban vs. VKA. The primary endpoint (per-protocol population) was time to first occurrence of all-cause death, stroke, or International Society of Thrombosis and Haemostasis-defined major bleeding during the period from the end of the ablation procedure to end of treatment (90 days). Overall, 632 patients were enrolled, 614 randomized, and 553 received study drug and underwent ablation; 177 subjects underwent brain magnetic resonance imaging to assess silent cerebral infarcts. The primary endpoint (only major bleeds occurred) was observed in 0.3% (1 patient) on edoxaban and 2.0% (2 patients) on VKA [hazard ratio (95% confidence interval): 0.16 (0.02-1.73)]. In the ablation population (modified intent-to-treat population including patients with ablation), the primary endpoint was observed in 2.7% of edoxaban (N = 10) and 1.7% of VKA patients (N = 3) between start of ablation and end of treatment. There were one ischaemic and one haemorrhagic stroke, both in patients on edoxaban. Cerebral microemboli were detected in 13.8% (16) patients who received edoxaban and 9.6% (5) patients in the VKA group (nominal P = 0.62).ConclusionUninterrupted edoxaban therapy represents an alternative to uninterrupted VKA treatment in patients undergoing AF ablation.

| S-EPMC6754569 | biostudies-literature

Edoxaban in patients with non-valvular atrial fibrillation after percutaneous coronary intervention: ENCOURAGE-AF design.

Project description:Approximately one fifth of patients diagnosed with atrial fibrillation (AF) undergo a percutaneous coronary intervention (PCI). Current guidelines recommend different combinations and durations of triple or dual antithrombotic therapy for these patients but data on the implementation of these recommendations in clinical routine are scarce. ENCOURAGE-AF is a prospective, non-interventional, non-comparative, multicentre study. Approximately 720 patients will be consecutively enrolled from 70 participating sites across Germany. Patients with non-valvular AF treated with edoxaban, who have undergone successful PCI, have no planned elective cardiac intervention during the study period, have capability, availability, and willingness for follow-up by telephone interview during the study, are aged ≥ 18 years with life expectancy ≥ 1 year, and provide written informed consent, will be included. Eligible patients will be enrolled between 4- and 72-h after completing a successful PCI. Duration of exposure to and dosing regimens of edoxaban, antiplatelet agents and other concomitant medications of interest will be monitored in line with the clinical practice. Physician- and patient-reported clinical events, adverse drug reactions, patient quality of life (EQ-5D-5L) and health resource utilisation (HRU) parameters will be evaluated at 30 days and 1-year post-PCI. The ENCOURAGE-AF non-interventional study will provide insights into the patterns of edoxaban usage in combination with antiplatelet treatment and other concomitant medications in AF patients with a successful PCI over a 1-year time period during routine clinical practice in Germany. The effectiveness and safety of edoxaban in this patient population, as well as patients' quality of life and HRU will be evaluated.Trial registration: Clinicaltrial.gov NCT04519944, registered on 20 August 2020.

| S-EPMC10600182 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data