Edoxaban enfolded beta-1,4-Poly-D-glucosamine nanoparticles for targeting ponym Stuart-Prower factor for treatment of venous thrombosis.

The present research looked for ways to develop shielded nanoparticles (NPs)-drug transporters made of chitosan (CS) to enhance the bioavailability of Edoxaban tosylate monohydrate (ETM) for oral administration by examining the correlation among design aspects and data from experiments using response surface methodology. ETM-loaded CS nanoparticles (ETM-CS-NPs) were developed using the ionic gelation of CS with tripolyphosphate (TPP). Utilizing Zeta-sizer and scanning electron microscopy, the ETM-CS-NPs were evaluated for particle size (PS), zeta potential (ZP), surface morphology, polydispersity index (PDI), entrapment efficiency (EE), and drug loading (DL). Drug and polymer interactions in NPs were assessed using Fourier transform infrared spectroscopy. The response surface approach and Design-Expert software optimized the ETM-CS-NPs. Using response surface methodology, the effects of independent variables such as the amount of CS, the amount of TPP, and the amount of glacial acetic acid on PS, PDI, and ZP were analyzed. The optimal combination of PS (354.8 nm), PDI (0.509), ZP (43.7 + mV), % EE (70.3 ± 1.3), and % DL (9.1 ± 0.4) has been identified for the optimized ETM-CS-NPs. ETM-CS-NPs' anticoagulant activity was evaluated using activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT) assays. In conclusion, a practical and consistent method has been established, and its application has been proven in vitro, indicating its utility for future studies of the biological distribution of ETM-CS-NPs in vivo for specific antithrombotic treatments.

Effectiveness of Novel Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke and systemic embolism (SE). Anticoagulation therapy, particularly with vitamin K antagonists (VKA) or novel oral anticoagulants (NOACs), is essential for stroke prevention in patients with AF. However, the comparative effectiveness of NOACs and warfarin remains debatable. Of the 34 studies included, 14 studies involving 166,845 patients were included in the meta-analysis and 20 studies were included in the systematic review. Our findings indicate that NOACs were associated with a significantly lesser risk of stroke/SE with a relative risk (RR) of 0.84 and p=0.0005, and all-cause mortality RR=0.88 and p=0.006. There were no significant differences between major bleeding events with an RR of 0.87 and p=0.22, and serious adverse events (SAE) with RR=1.01 and p=0.35, compared to warfarin in patients with AF. Our meta-analysis demonstrates strong evidence for the superiority in reducing stroke/SE and all-cause mortality of NOACs compared to warfarin. However, no significant differences were identified in the bleeding outcomes or SAEs between the two groups.

The effectiveness and safety of Rivaroxaban and Edoxaban in the treatment of lower extremity deep vein thrombosis.

INTRODUCTION: Deep vein thrombosis (DVT) is a medical condition characterized by forming a blood clot, or thrombus, in one of the deep veins, typically in the legs. It is a type of venous thromboembolism (VTE), which refers to the formation of blood clots in the veins. It is caused by Virchow's triad (stasis, hypercoagulation, and endothelial injury). OBJECTIVE: Our main objective is to explore the effectiveness and safety of Rivaroxaban and Edoxaban in treating lower extremity deep vein thrombosis. METHODS: We conducted a retrospective study involving 406 patients subjected to DVT treatment using DOACs (Edoxaban and Rivaroxaban) at our hospital. We recruited adult patients (18 years and above) diagnosed with lower extremity deep vein thrombosis and received treatment with either Rivaroxaban or Edoxaban as the primary anticoagulant therapy for DVT. We excluded patients who received treatment with other anticoagulant medications (warfarin heparin) as the primary therapy for DVT. RESULTS: The groups showed statistically significant differences in red blood cell count and haemoglobin levels, with the Edoxaban group having high values. However, the two groups observed no statistically significant differences in creatinine clearance, white blood cell count, platelet count, C-reactive protein, and D-dimer levels. The difference in the incidence of PE between the two groups was statistically significant (P value < 0.001). The Edoxaban group had fewer PE patients than the rivaroxaban group. The reduction in recurrent thrombosis was significantly higher in the rivaroxaban group compared to the Edoxaban group. There were no significant differences in the major bleeding at various sites across the two treatment groups (p > 0.05). CONCLUSION: Rivaroxaban's pharmacokinetic profile includes rapid absorption and a relatively short half-life. It means that once administered, Rivaroxaban quickly reaches its peak concentration in the blood and is subsequently eliminated from the body within a relatively short period. Edoxaban's pharmacokinetic profile may include slower absorption and a longer half-life than Rivaroxaban. It can result in a slower rate of achieving peak concentration and a more prolonged presence in the bloodstream. These results emphasize the need for careful consideration of anticoagulant therapy in patients with underlying cancer and underscore the importance of managing risks while providing adequate anticoagulation to prevent thrombotic events.

Adverse events of direct factor Xa inhibitors: a disproportionality analysis of the FAERS database.

OBJECTIVES: Direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, commonly used direct oral anticoagulant (DOAC), are widely used to prevent and treat stroke and venous thromboembolic events in patients with atrial fibrillation (AF). This study aimed to assess and compare reports of adverse events associated with rivaroxaban, apixaban, and edoxaban, including hemorrhagic and non-hemorrhagic events. METHODS: Reporting odds ratio (ROR), proportional reporting ratio (PRR), Medications and Health Care Products Regulatory Agency (MHRA), and the information component (IC) were used to perform a risk assessment of adverse event reports in the FDA Adverse Event Reporting System (FAERS) database for the years 2018-2022. RESULTS: Combined with disproportionality analysis in different backgrounds, the salient risks of the three-factor Xa inhibitors varied. Rivaroxaban had the most significant risk of hemorrhage, apixaban had a higher incidence and risk of death, cardiac and cerebral adverse events, and edoxaban showed a more prominent risk in the kidneys and urinary system. CONCLUSION: Hemorrhage is a common risk with factor Xa inhibitors, with rivaroxaban being the most significant. Apixaban and edoxaban also showed significant association with non-hemorrhagic adverse events, and increased attention to non-hemorrhagic adverse events is needed in clinical use.

Incidence and Predictors of Worsening Renal Function in Edoxaban-Treated Atrial Fibrillation Patients Within ETNA-AF-Europe Registry.

Background: Managing patients with atrial fibrillation (AF) and worsening renal function (WRF) remains a clinical challenge due to the need of dose adjustment of non-vitamin K antagonist oral anticoagulants. Objectives: To determine the incidence of WRF in patients with AF treated with edoxaban, the association of WRF with clinical outcomes, and predictors of WRF and clinical outcomes in these patients. Methods: This is a subanalysis of the Edoxaban Treatment in routiNe clinical prActice for patients with non-valvular Atrial Fibrillation in Europe study (NCT02944019), an observational study of edoxaban-treated patients with AF. WRF was defined as a ≥25% reduction in creatinine clearance between baseline and 2 years. Results: Of the 9,054 patients included (69% of the total 13,133 enrolled), most did not experience WRF (90.3%) during the first 2 years of follow-up. WRF occurred in 9.7% of patients. Patients with WRF had significantly higher rates of all-cause death (3.88%/y vs 1.88%/y; P < 0.0001), cardiovascular death (2.09%/y vs 0.92%/y; P < 0.0001), and major bleeding (1.51%/y vs 0.98%/y; P = 0.0463) compared with those without WRF. Rates of intracranial hemorrhage (0.18%/y vs 0.18%/y) and of any stroke/systemic embolic events were low (0.90%/y vs 0.69%/y; P = 0.3161) in both subgroups. The strongest predictors of WRF were a high CHA2DS2-VASc score, high baseline creatinine clearance, low body weight, and older age. Most predictors of WRF were also predictors of clinical outcomes. Conclusions: WRF occurred in approximately 10% of edoxaban-treated AF patients. Rates of death and major bleeding were significantly higher in patients with WRF than without. Stroke events were low in both subgroups.

Periprocedural Edoxaban Management and Clinical Outcomes in Patients Undergoing Transcatheter Cardiovascular Procedures in the EMIT-AF/VTE Program.

Clinical trial registration number: NCT02950168, NCT02951039.

Optimal Dose of Edoxaban for Very Elderly Atrial Fibrillation Patients at High Risk of Bleeding: The LEDIOS Registry.

BACKGROUND AND OBJECTIVES: Optimal anticoagulation in very elderly patients is challenging due to the high risk of anticoagulant-induced bleeding. The aim of this study was to assess outcomes of on-label reduced-dose edoxaban (30 mg) in very elderly patients who had additional risk factors for bleeding. METHODS: This was a multi-center, prospective, non-interventional observational study to evaluate the efficacy and safety of on-label reduced-dose edoxaban in atrial fibrillation (AF) patients 80 years of age or older and who had more than 1 risk factor for bleeding. RESULTS: A total of 2448 patients (mean age 75.0±8.3 years, 801 [32.7%] males) was included in the present study, and 586 (23.9%) were 80 years of age or older with additional risk factors for bleeding. Major bleeding events occurred frequently among very elderly AF patients who had additional bleeding risk factors compared to other patients (unadjusted hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.16-4.02); however, there were no significant differences in stroke incidence (HR, 1.86; 95% CI, 0.98-3.55). There were no significant differences for either factor after adjusting for age and sex (adjusted HR, 1.65; 95% CI, 0.75-3.62 for major bleeding; adjusted HR, 1.13; 95% CI, 0.51-2.50 for stroke). CONCLUSIONS: In very elderly AF patients with comorbidities associated with greater risk of bleeding, the incidence of major bleeding events was significantly increased. In addition, risk of stroke showed tendency to increase in same population. Effective anticoagulation therapy might be important in these high-risk population, and close observation of bleeding events might also be required. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03554837.

Edoxaban Improved End-QRS Notches and Early Repolarizations.

Cardiac computed tomography (CT) images sometimes show a donut-like oval structure on the antero-superior wall of the left atrium (LA). What is a donut? Left atrium diverticula (LADs) are common, but there are many unknown features of LADs. The direct effects of pulmonary vein thrombi (PVTs) on the heart are poorly understood. Herein, we report a case report in which we describe the different effects of edoxaban on LA thrombi, the LAD, coronary artery collaterals, early repolarizations, and end-QRS notches using cardiac CT and transesophageal echocardiography (TEE). First, we showed that there was a LAD on the anterior wall of the LA where the LA thrombi from the right lower pulmonary vein (RLPV) thrombi were connected. To our knowledge, this is the first report to reveal LAD's annular transformation and the beneficial effect of edoxaban on the end-QRS notch.

Oral Anticoagulation Use in Individuals With Atrial Fibrillation and Chronic Kidney Disease: A Review.

Atrial fibrillation (AF) is highly prevalent in patients with chronic kidney disease (CKD). It is associated with an increased risk of stroke, which increases as kidney function declines. In the general population and in those with a moderate degree of CKD (creatinine clearance 30-50 mL/min), the use of oral anticoagulation to decrease the risk of stroke has been the standard of care based on a favorable risk-benefit profile that had been established in seminal randomized controlled trials. However, evidence regarding the use of oral anticoagulants for stroke prevention is less clear in patients with severe CKD (creatinine clearance <30 mL/min) and those receiving maintenance dialysis, as these individuals were excluded from such large randomized controlled trials. Nevertheless, the direct oral anticoagulants have invariably usurped vitamin K antagonists as the preferred choice for oral anticoagulation among patients with AF across all strata of CKD based on their well-defined safety and efficacy and multiple pharmacokinetic benefits (e.g., less drug-drug interactions). This review summarizes the current literature on the role of oral anticoagulation in the management of AF among patients with CKD and highlights current deficiencies in the evidence base and how to overcome them.

D-dimer cut-off value for predicting venous thromboembolism at the initial diagnosis in Japanese patients with advanced lung cancer.

OBJECTIVE: Cancer is a well-known risk factor for venous thromboembolism. The D-dimer level is used to predict venous thromboembolism; however, reports on an appropriate D-dimer cut-off value in Japanese patients with advanced lung cancer are lacking. Therefore, this study aimed to calculate the D-dimer cut-off value for venous thromboembolism at the time of lung cancer diagnosis. METHODS: The Rising-venous thromboembolism/NEJ037 study was a multicenter, prospective observational study. Patients with lung cancer who were contraindicated for radical resection or radiation were enrolled and followed up for 2 years. In the present study (jRCT no. 061180025), a receiver operating characteristic curve for D-dimer levels was created using the dataset of the Rising-venous thromboembolism/NEJ037 study. RESULTS: The Rising-venous thromboembolism/NEJ037 study included a total of 1008 patients, of whom 976, whose D-dimer levels had been measured at the time of cancer diagnosis, were included in the present study. At the time of lung cancer diagnosis, 62 (6.3%) and 914 (93.7%) patients presented with and without venous thromboembolism, respectively. The D-dimer values ranged from 0.1 to 180.1 µg/ml and from 0.1 to 257.2 µg/ml in patients with and without venous thromboembolism, respectively. The receiver operating characteristic curve was discriminative with a cut-off value of 3.3 µg/ml and an area under the curve of 0.794 (sensitivity, 0.742; specificity, 0.782; 95% confidence interval, 0.725-0.863). CONCLUSIONS: This is the first study to calculate the D-dimer cut-off value in Japanese patients with advanced lung cancer. Patients with D-dimer levels ≥3.3 µg/ml at the time of initial diagnosis may have coexisting venous thromboembolism.

Role of a National Health Service Electronic Prescriptions Database in the Detection of Prescribing and Dispensing Issues and Adherence Evaluation of Direct Oral Anticoagulants.

BACKGROUND: Anticoagulation therapy plays a crucial role in the management of atrial fibrillation (AF) by significantly reducing the risk of stroke. Direct oral anticoagulants (DOAC) became preferred over warfarin due to their superior safety and efficacy profile. Assessing adherence to anticoagulation therapy is necessary in clinical practice for optimising patient outcomes and treatment efficacy, thus emphasising its significance. METHODS: A retrospective study utilised the Latvian National Health Service reimbursement prescriptions database, covering prescriptions for AF and flutter from January 2012 to December 2022. The proportion of days covered method was selected for adherence assessment, categorising it into three groups: (1) below 80%, (2) between 80% and 90%, and (3) above 90%. RESULTS: A total of 1,646,648 prescriptions were analysed. Dabigatran prescriptions started declining after 2020, coinciding with a decrease in warfarin prescriptions since 2018. The total adherence levels to DOAC therapy were 69.4%. Only 44.2% of users achieved an adherence level exceeding 80%. The rate of paper prescriptions decreased from 98.5% in 2017 to 1.3% in 2022. Additionally, the utilisation of international non-proprietary names reached 79.7% in 2022. Specifically, 16.7% of patients selected a single pharmacy, whereas 27.7% visited one or two pharmacies. Meanwhile, other patients obtained medicines from multiple pharmacies. CONCLUSIONS: The total adherence level to DOAC therapy is evaluated as low and there was no significant difference in age, gender, or "switcher" status among adherence groups. Physicians' prescribing habits have changed over a decade.

Long-term effectiveness and safety of edoxaban in patients with atrial fibrillation: 4-year data from the ETNA-AF-Europe study.

BACKGROUND: To assess long-term effectiveness and safety of edoxaban in Europe. METHODS AND RESULTS: ETNA-AF-Europe, a prospective, multinational, multi-centre, post-authorisation, observational study was conducted in agreement with the European Medicines Agency. The primary and secondary objectives assessed real-world safety (including bleeding and deaths) and effectiveness (including stroke, systemic embolic events and clinical edoxaban use), respectively. Median (interquartile range) age of the 13,164 patients was 75.0 (68.0-80.0) years; CHA2DS2-VASc and HAS-BLED scores were 3.0 (2.0-4.0) and 2.0 (1.0-2.0), respectively. Follow-up duration was 3.98 (3.21-4.05) years. Patients on edoxaban 30 mg (n = 3042) at baseline were older (80.0 vs 73.0 years), more likely assessed as frail by investigators (27.0% vs 6.6%) and had more comorbidities than those on edoxaban 60 mg (n = 9617; missing dosing information for n = 505). Annualised event rates of all-cause and cardiovascular death in the overall population, edoxaban 60 mg and edoxaban 30 mg groups were 4.1%, 2.8% and 8.4%, and 1.0%, 0.7% and 2.0%, respectively. Annualised rates of stroke were relatively constant throughout the follow-up, transient ischaemic attack and systemic embolism were < 1% in the overall population. Rates of any major and major gastrointestinal bleeding were low, with slightly higher rates for edoxaban 30 vs 60 mg group. Intracranial haemorrhage was uncommon (0.2%). CONCLUSIONS: In European patients with AF, long-term therapy with edoxaban is associated with low and relatively constant annualised rates of stroke and major bleeding. Differences in outcomes between the two approved doses are attributable to differences in clinical characteristics.

Interactions between antiepileptic drugs and direct oral anticoagulants for primary and secondary stroke prevention.

INTRODUCTION: Direct oral anticoagulants (DOAC) are the guideline-recommended therapy for prevention of stroke in atrial fibrillation (AF) and venous thromboembolism. Since approximately 10% of patients using antiepileptic drugs (AED) also receive DOAC, aim of this review is to summarize data about drug-drug interactions (DDI) of DOAC with AED by using data from PubMed until December 2023. AREAS COVERED: Of 49 AED, only 16 have been investigated regarding DDI with DOAC by case reports or observational studies. No increased risk for stroke was reported only for topiramate, zonisamide, pregabalin, and gabapentin, whereas for the remaining 12 AED conflicting results regarding the risk for stroke and bleeding were found. Further 16 AED have the potential for pharmacodynamic or pharmacokinetic DDI, but no data regarding DOAC are available. For the remaining 17 AED it is unknown if they have DDI with DOAC. EXPERT OPINION: Knowledge about pharmacokinetic and pharmacodynamic DDI of AED and DOAC is limited and frequently restricted to in vitro and in vivo findings. Since no data about DDI with DOAC are available for 67% of AED and an increasing number of patients have a combined medication of DOAC and AED, there is an urgent need for research on this topic.

Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulants.

Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs. This review is aimed at analyzing the scientific literature on the gene polymorphisms involved in the metabolism of DOACs. We searched PubMed, Cochrane, Google Scholar, and CyberLeninka (Russian version) databases with keywords: 'dabigatran', 'apixaban', 'rivaroxaban', 'edoxaban', 'gene polymorphism', 'pharmacogenetics', 'ABCB1', 'CES1', 'SULT1A', 'ABCG2', and 'CYP3A4'. The articles referred for this review include (1) full-text articles; (2) study design with meta-analysis, an observational study in patients taking DOAC; and (3) data on the single-nucleotide polymorphisms and kinetic parameters of DOACs (plasma concentration), or a particular clinical outcome, published in English and Russian languages during the last 10 years. The ages of the patients ranged from 18 to 75 years. Out of 114 reviewed works, 24 were found eligible. As per the available pharmacogenomic data, polymorphisms affecting DOACs are different. This may aid in developing individual approaches to optimize DOAC pharmacotherapy to reduce the risk of hemorrhagic complications. However, large-scale population studies are required to determine the dosage of the new oral anticoagulants based on genotyping. Information on the genetic effects is limited owing to the lack of large-scale studies. Uncovering the mechanisms of the genetic basis of sensitivity to DOACs helps in developing personalized therapy based on patient-specific genetic variants and improves the efficacy and safety of DOACs in the general population.

Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulantsAtrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs.

Edoxaban for 12 Versus 3 Months in Cancer-associated Isolated Distal Deep Vein Thrombosis According to Different Doses: Insights from the ONCO DVT study.

BACKGROUND: The ONCO DVT study revealed the superiority of 12-month relative to 3-month edoxaban treatment for cancer-associated isolated distal deep vein thrombosis (DVT) regarding the thrombotic risk. METHODS: In this pre-specified subgroup analysis of the ONCO DVT study, we stratified the patients into those with a standard edoxaban dose (60 mg/day; N=151) and those with a reduced edoxaban dose (30 mg/day; N=450) and evaluated the clinical outcomes for the 12-month and 3-month treatments. RESULTS: The cumulative 12-month incidence of symptomatic recurrent venous thromboembolism was lower in the 12-month than 3-month group for both the 60 mg (1.3% vs. 11.6%, P=0.02; odds ratio [OR], 0.12; 95% CI, 0.01-0.97) and 30 mg (1.1% vs. 7.6%, P=0.002; OR, 0.14; 95% CI, 0.03-0.60) edoxaban subgroups, which was consistent across the edoxaban doses without a significant interaction (P =0.90). The 12-month cumulative incidence of major bleeding was higher in the 12-month group than 3-month group for the 60 mg edoxaban subgroup (14.3% vs. 4.4%, P=0.046; OR, 3.61; 95% CI, 0.97-13.52), whereas it did not significantly differ between the two groups for the 30 mg edoxaban subgroup (8.7% vs. 8.6%, P=0.89; OR, 0.97; 95% CI, 0.49-1.91), signaling there was a potential interaction (P=0.07). CONCLUSIONS: A 12-month edoxaban regimen for cancer-associated isolated distal DVT was consistently superior to a 3-month regimen, across the edoxaban doses for the thrombotic risk. However, caution was suggested for the standard dose of edoxaban due to the potential for an increased risk of bleeding with prolonged anticoagulation therapy.

Safety and efficacy of direct oral anticoagulants in comparison to warfarin in obese patients with atrial fibrillation: A systematic review and meta-analysis.

Background and Aim: Obesity affects nearly 650 million adults worldwide, and the prevalence is steadily rising. This condition has significant adverse effects on cardiovascular health, increasing the risk of hypertension, coronary artery disease, heart failure, and atrial fibrillation (AF). While anticoagulation for obese patients with AF is a well-established therapy for the prevention of thromboembolism, the safety and efficacy of different anticoagulants in this specific population are not well explored. This meta-analysis aimed to compare direct oral anticoagulants (DOAC) to vitamin K antagonists in obese populations with AF. Methods: The PRISMA guidelines were followed for this meta-analysis, registered in PROSPERO (CRD42023392711). PubMed, PubMed Central, Embase, Cochrane Library, and Scopus databases were searched for relevant articles from inception through January 2023. Two independent authors screened titles and abstracts, followed by a full-text review in Covidence. Data were extracted in Microsoft Excel and analyzed using RevMan v5.4 using odds ratio as an effect measure. Results: Two thousand two hundred fifty-nine studies were identified from the database search, and 18 were included in the analysis. There were statistically significant reductions in the odds of ischemic and hemorrhagic stroke in the DOAC group compared with the VKA group (OR 0.70, CI 0.66-0.75) and (OR 0.47, CI 0.35-0.62), respectively. In addition, the DOAC group exhibited lower odds of systemic embolism (OR 0.67, CI 0.54-0.83), major bleeding (OR 0.62, CI 0.54-0.72), and composite outcome (OR 0.72, CI 0.63-0.81). Conclusion: Based on the findings from this meta-analysis, DOACs demonstrate superior safety and efficacy in obese patients with AF compared with VKAs. These results may have significant implications for guiding anticoagulation strategies in this patient population.

Prescribing Patterns and Outcomes of Edoxaban in Atrial Fibrillation Patients From Asia　- One-Year Data From the Global ETNA-AF Program.

Background: This study reports prescribing patterns and the 1-year effectiveness and safety of edoxaban in an Asian cohort of Edoxaban Treatment in routiNe clinical prActice (ETNA)-Atrial Fibrillation (AF) patients. Methods and Results: The Global ETNA-AF program integrates prospective, observational, noninterventional regional studies, collecting data on characteristics and clinical outcomes of patients with AF receiving edoxaban for stroke prevention. Baseline characteristics, medical history, and 1-year clinical event rates were assessed in patients from South Korea, Taiwan, Hong Kong, and Thailand. Clinically relevant events assessed at 12 months included all-cause death, cardiovascular death, ischemic and hemorrhagic stroke, systemic embolic events (SEEs), bleeding, and net clinical outcome (NCO). Overall, 3,359 patients treated with edoxaban 60 or 30 mg once daily completed 1-year follow-up; 70.9% of patients received recommended dosing according to local labels. Baseline mean±standard deviation age was 71.7±9.6 years, CHA2DS2-VASc score was 3.1±1.5, and modified HAS-BLED score was 2.3±1.1. Mean age and sex were similar across countries/regions. The 1-year event rate for all-cause death was 1.8%; major bleeding, 1.3%; ischemic stroke, 1.1%; cardiovascular mortality, 0.7%; hemorrhagic stroke, 0.3%; SEEs, 0%; and NCO, 4.1%; with differences observed between countries/regions and dosing groups. Conclusions: Most Asian patients with AF were prescribed recommended edoxaban dosing in routine care settings. At 1-year follow-up, this analysis supports the effectiveness and safety of edoxaban in these patients.

Edoxaban for the treatment of hypercoagulability and cerebral thromboembolism associated with cancer: A randomized clinical trial of biomarker targets.

BACKGROUND: This study aimed compare efficacy of edoxaban and enoxaparin upon biomarkers of hypercoagulability in patients with cancer-related embolic stroke of undetermined source (ESUS). METHODS: In this open-label, randomized, pilot trial, patients with cancer-related ESUS within 30 days of diagnosis were randomly assigned (1:1) to receive edoxaban (60 mg once daily) or enoxaparin (1 mg/kg twice daily) for 90 days. The primary endpoint was interval change of serum D-dimer level between days 0 and 7. The secondary endpoints were microembolic signals detected by transcranial Doppler at 7 and 90 days, the modified Rankin scale score, and stroke recurrence during 90 days. Safety outcomes included major bleeding and all-cause death at 90 days. RESULTS: Of 303 patients with ischemic stroke and cancer, 40 fully met enrollment criteria and were randomized. Baseline D-dimer levels were numerically higher in the edoxaban group (22.9 ± 15.9 µg/mL vs 16.9 ± 16.9 µg/mL). D-dimer level change (%) between days 0 and 7 was similar in the two groups (53.2 ± 25.7 vs 52.2 ± 52.0; P = 0.11). Microembolic signals were detected in 41.1% and 43.8% at baseline, 41.2% and 42.9% at day 7, and 25.0% and 28.6% at day 90 in the edoxaban and enoxaparin groups, respectively. Non-significantly higher major bleeding (35.0% vs 10.0%, P = 0.06) and 90-day mortality (40.0% vs 25.0%, P = 0.31) were noted in the edoxaban group. CONCLUSION: Edoxaban and enoxaparin were comparable with respect to the biomarkers of hypercoagulability and cerebral thromboembolism. Larger trials are warranted to compare effects of edoxaban and enoxaparin upon recurrent stroke and major bleeding in patients with cancer-related ESUS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03570281 (https://clinicaltrials.gov/ct2/show/NCT03570281).

Effectiveness and Safety of Edoxaban Compared With Apixaban in Elderly Patients With Nonvalvular Atrial Fibrillation: A Real-World Population-Based Cohort Study.

BACKGROUND: The very elderly (≥80 years) are at high risk of nonvalvular atrial fibrillation and thromboembolism. Given its recent approval, the comparative effectiveness and safety of edoxaban in this population, relative to the commonly used apixaban, remain unknown. METHODS: Using the United Kingdom Clinical Practice Research Datalink, we identified a cohort of patients aged ≥80 with incident nonvalvular atrial fibrillation and newly treated with edoxaban or apixaban between 2015 and 2021. Cohort entry was defined as the first prescription for one of the 2 drugs. We used propensity score fine stratification and weighting for confounding adjustment. A weighted Cox proportional hazards model was used to estimate the hazard ratios (HR) with 95% CI of ischemic stroke/transient ischemic attack/systemic embolism (primary effectiveness outcome) and of major bleeding (primary safety outcome) associated with edoxaban compared with apixaban. We also assessed the risk of all-cause mortality and a composite outcome of ischemic stroke/transient ischemic attack, systemic embolism, gastrointestinal bleeding, and intracranial hemorrhage as secondary outcomes. RESULTS: The cohort included 7251 new-users of edoxaban and 39 991 of apixaban. Edoxaban and apixaban had similar incidence rates of thromboembolism (adjusted rates, 20.38 versus 19.22 per 1000 person-years; adjusted HR, 1.06 [95% CI, 0.89-1.26]), although the rates of major bleeding were higher with edoxaban (adjusted rates, 45.57 versus 31.21 per 1000 person-years; adjusted HR, 1.42 [95% CI, 1.26-1.61]). The risk of the composite outcome was 21% higher with edoxaban (adjusted HR, 1.21 [95% CI, 1.07-1.38]). All-cause mortality was similar between edoxaban and apixaban (adjusted HR, 1.04 [95% CI, 0.96-1.12]). CONCLUSIONS: In very elderly patients with nonvalvular atrial fibrillation, edoxaban resulted in similar thromboembolism prevention as apixaban, although it was associated with a higher risk of major bleeding. These findings may improve the management of nonvalvular atrial fibrillation by informing physicians on the choice of anticoagulant for this vulnerable population.