Successful direct oral anticoagulant management of asymptomatic superior mesenteric vein thrombosis after adjuvant chemotherapy for colorectal cancer patient: A case report.

Owing to advances in cancer treatment and the diversification of treatment methods, cancer-associated thrombosis is increasing. Cancer can cause blood clots by activating the blood clotting system, increasing clotting factors through inflammation, reducing blood flow due to immobilization and damaging blood vessels through treatments such as chemotherapy. In clinical practice, superior mesenteric vein (SMV) thrombosis is occasionally observed in patients with cancer; however, certain cases of asymptomatic thrombosis can be serious. In the present case, a 71-year-old woman underwent laparoscopic high anterior resection for colorectal cancer. The patient received capecitabine as postoperative adjuvant chemotherapy for 6 months. Contrast-enhanced CT after the completion of chemotherapy revealed a sizable thrombus in the SMV. The thrombus occupied the SMV lumen without evident intestinal ischemia. D-dimer levels were elevated. Since the patient remained asymptomatic, edoxaban (30 mg/day) was administered in an outpatient setting. Six months later, contrast-enhanced CT confirmed thrombus resolution. No hemorrhagic events were observed during edoxaban treatment. In conclusion, cancer and chemotherapy are risk factors for thrombosis, indicating that regular D-dimer measurements may be necessary during cancer treatment. In addition, edoxaban may be an effective therapeutic tool for SMV thrombosis during chemotherapy for cancer.

Risk of gastrointestinal bleeding in Asian patients receiving oral anticoagulants for stroke prevention in atrial fibrillation.

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in atrial fibrillation. At the Asia Pacific Advancing Patient care with EdoXaban 2023 meeting, experts shared insights on gastrointestinal bleeding with NOACs for stroke prevention in atrial fibrillation in Asian clinical practice, where NOACs have gained widespread acceptance due to their favourable profiles. Gastrointestinal bleeding risk varies amongst NOACs, emphasizing the importance of diligent patient assessment, dosage selection and vigilant monitoring. Edoxaban emerged as a viable option with a low gastrointestinal bleeding risk profile in Asian compared with non-Asian patients, supporting its continued clinical utilization for appropriate patients.

Assessing Direct Oral Anticoagulants in the Clinical Laboratory.

Direct oral anticoagulants (DOACs) have significant advantages over vitamin K antagonists including lack of need for routine laboratory monitoring. However, assessment of DOAC effect and concentration may be important to guide clinical management including need for DOAC reversal, particularly in acute or emergent situations. In this manuscript, the authors describe tests to screen for DOAC presence and tests that have demonstrated equivalence to gold standard testing for quantifying DOAC exposure. They also discuss the effect of DOACs on other coagulation assays and strategies for monitoring unfractionated heparin in patients with concomitant DOAC exposure.

Can edoxaban be used at extremes of bodyweight and in patients with a creatinine clearance ≥95 ml/min? - A population pharmacokinetic analysis.

BACKGROUND: Clinical evidence surrounding edoxaban use in patients weighing <50 kg and >120 kg is lacking. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee suggests avoiding edoxaban in patients >120 kg. Additionally, concerns exist regarding decreased efficacy in patients prescribed edoxaban for atrial fibrillation with a creatinine clearance (CrCl) >95 ml/min, a finding of the ENGAGE AF-TIMI 48 trial when edoxaban was compared to warfarin. OBJECTIVE: To derive a population pharmacokinetic (PopPK) model using clinical practice data, to understand the impact of bodyweight and renal function on edoxaban pharmacokinetics. METHOD: Edoxaban plasma concentrations and patient characteristics were collated from King's College Hospital anticoagulation clinics between 11/2016 and 08/2022. A PopPK model was developed using non-linear mixed effects modelling and used to simulate edoxaban concentrations at the extremes of bodyweight and with varying renal function. RESULTS: Data from 409 patients (46 < 50 kg, 34 > 120 kg and 123 with a CrCl > 95 ml/min) provided 455 edoxaban plasma concentrations. A one-compartment model with between-subject variability on clearance with a proportional error model best described the data. The most significant covariates impacting on edoxaban exposure were CrCl and bodyweight. Our work suggests that edoxaban exposure in patients weighing up to 140 kg is comparable to those weighing 75 kg. Edoxaban exposure is reduced in patients weighing <50 kg due to the recommended dose reductions. There is also a reduction in AUCss when CrCl > 95 ml/min compared to CrCl 80 ml/min. CONCLUSIONS: Our population PK model for edoxaban suggests that renal function is a key driver for overall edoxaban exposure. Further clinical outcome data is required to understand clinical effectiveness and adverse outcomes.

Randomized Comparison of Progression of Atherosclerotic Plaques and Calcification of Coronary Artery in Atrial Fibrillation Patients Treated With Edoxaban Versus Warfarin (The REPRESENT-AF trial).

Although the adverse effects of long-term use of vitamin K oral anticoagulant (OAC), warfarin, on the coronary vasculature are well-established, it remains unknown whether nonvitamin K oral anticoagulants play a role in the attenuation of plaque progression and coronary calcification. This study aimed to compare the changes in atherosclerotic plaques and calcification of the coronary arteries in patients with atrial fibrillation (AF) treated with edoxaban and warfarin. A total of 150 OAC-naïve patients with AF and atherosclerotic lesions on coronary computed tomography angiography (CCTA) were enrolled and randomly assigned to the edoxaban or warfarin treatment groups. All enrolled patients received rosuvastatin 10 mg and 119 patients completed the entire study protocol. A total of 12 months after the assigned OAC treatment, follow-up CCTA was performed and changes in plaque and calcium volumes of the coronary arteries were analyzed. The baseline characteristics of the 2 groups were well-balanced. The percentage of time in therapeutic range in the warfarin group was 61.1%. Compared with the baseline CCTA, there was a significant reduction in plaque volume after 12 months of OAC and rosuvastatin administration in both groups, and the extent of regression did not differ significantly between the groups. The increase in calcium volume was greater in the warfarin group than in the edoxaban group; however, the difference was not significant. In OAC-naïve patients with AF and atherosclerotic coronary lesions who were treated with moderate-intensity statin, edoxaban use did not have a positive effect on atherosclerotic plaques and coronary calcification compared with warfarin use over a 12-month follow-up period.

Risk of ocular neovascular conversion and systemic bleeding complications in patients with AMD on DOACs or Warfarin.

PURPOSE: Conversion to neovascular disease in patients with non-neovascular age-related macular degeneration (AMD) initiated on direct oral anticoagulants (DOAC) compared to matched patients treated with warfarin. DESIGN: Retrospective cohort study. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: The study included 20,300 patients and 13,387 patients with non-neovascular AMD initiated on DOACs or warfarin, respectively, before propensity score matching (PSM). METHODS, INTERVENTION, OR TESTING: TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with non-neovascular AMD stratified by treatment with DOACs or warfarin with at least six months of follow-up. Propensity score matching was performed to control for baseline demographics and medical comorbidities. MAIN OUTCOME MEASURES: Relative risk (RR) of developing neovascular AMD, macular hemorrhage (MH), vitreous hemorrhage (VH), and requiring an ocular intervention (intravitreal anti-vascular endothelial growth factor (VEGF) therapy or pars plana vitrectomy (PPV)) within six months and one year. Patients with chronic atrial fibrillation (AF) on anticoagulation were separately evaluated for the same measures within 5 years after initiating therapy. RESULTS: Treatment with warfarin was associated with higher risk of developing neovascular AMD at six months (RR,1.24, 95% CI, 1.12 - 1.39; P<.001) and one year (RR, 1.26, 95% CI, 1.14 - 1.40; P<.001) when compared to matched patients treated with DOACs. There was an increased risk of requiring intravitreal anti-VEGF therapy (6 months: RR, 1.30; 95% CI, 1.13-1.49; P<.001; 1 year: RR, 1.31, 95% CI, 0.72 - 2.05; P<.001) and PPV (6 months: RR, 1.16; 95% CI, 1.16-3.94; P = .01; 1 year: RR, 2.29, 95% CI, 1.30 - 4.05; P=.003). Among patients with AMD and AF treated with warfarin, there was an increased risk of ocular complications (neovascular AMD: RR, 1.25; 95% CI, 1.14-1.38; P<.001; MH: RR, 1.86; 95% CI, 1.47-2.35; P<.001; VH: RR, 2.22; 95% CI, 1.51-3.26; P<.001) and need for intravitreal anti-VEGF therapy (RR, 1.34; 95% CI, 1.18-1.52; P<.001) over an extended 5-year period. There was no significant difference in the development of major systemic hemorrhagic events between the two cohorts over five years. CONCLUSIONS: Patients with non-neovascular AMD treated with warfarin were more likely to develop neovascular disease and require ocular intervention for hemorrhagic complications when compared to matched patients initiated on DOACs.

Risk Factors for Anemia Exacerbation Requiring Red Blood Cell Transfusion During Edoxaban Thromboprophylaxis After Orthopedic Surgery.

Background An increased risk of anemia during edoxaban thromboprophylaxis in orthopedic surgery has been reported. However, the risk factors for the exacerbation of anemia requiring transfusion with irradiated red blood cell concentrates during postoperative edoxaban thromboprophylaxis remain unknown. Therefore, this study investigated the factors that increase the possibility of transfusion during edoxaban thromboprophylaxis after orthopedic surgery by reanalyzing clinical data from a previous collection. Methods A total of 221 patients who underwent total hip or knee arthroplasty at a single center between July 2011 and June 2012 were included in this study. Among these, 167 patients who received 30 mg of postoperative edoxaban thromboprophylaxis were retrospectively analyzed to identify critical factors for transfusion during edoxaban thromboprophylaxis after orthopedic surgery. Results Lower preoperative hemoglobin levels and higher intraoperative blood loss per body weight were significantly associated with an increase in the frequency of transfusion during postoperative edoxaban thromboprophylaxis. These factors were also potentially related to increased coagulation parameters during edoxaban thromboprophylaxis. Conclusion Our study shows that lower preoperative hemoglobin levels and higher intraoperative blood loss are associated with increased coagulation parameters with edoxaban thromboprophylaxis after orthopedic surgery and may lead to worsening of anemia, thereby requiring blood transfusion.

Arg-Specific serine Protease-Targeted edoxaban tosylate monohydrate-Poly (lactic-co-glycolic acid) Nanoparticles: Investigating Stuart-Prower factor targeting and intestinal distribution through Ex-Vivo fluorescent visualization.

The goal of the current study was to formulate and examine the potential of poly (lactic-co-glycolic acid) (PLGA) as carriers to facilitate the targeted administration of edoxaban tosylate monohydrate (ETM). ETM-PLGA-NPs were effectively formulated using the nanoprecipitation technique. Particle size, drug entrapment percentage, zeta potential, assessment of intestinal absorption, FT-IR, SEM, drug dissolution behavior, and histopathology investigations were used to describe ETM-PLGA-NPs. The produced NPs had a roughly spherical shape with a particle size of 99.85 d.nm, a PDI of 0.478, and a zeta potential of 38.5 mV with a maximum drug entrapment of 82.1 %. FTIR measurements showed that the drug's chemical stability remained intact after preapred into nanoparticles. In vitro drug release behavior followed the Higuchi model and revealed an early burst release of 30 % and persistent drug release of 78 % from optimized NPs for up to 120 hrs. According to in vitro data, a 1:10 ratio of ETM to PLGA provided longer-lasting ETM release and improved encapsulation efficiency. Images captured with an inverted fluorescent microscope exhibited that NPs may both greatly increase the amount of ETM accumulated in the intestinal tract and make it easier for ETM to enter the membrane beneath the cells of the intestines. The study found that using PLGA nanoparticles to encapsulate the ETM resulted in longer circulation duration (aPTT, PT, TT). In vivo investigations found that nanoparticles encapsulated had no negative impact on hematological parameters, lung, liver, or kidney tissues. All things considered, the NPs are a potential delivery method to increase the oral absorption and antithrombotic activity of ETM.

Andexanet Alfa for Edoxaban Reversal and Associated Thromboelastography Changes in Surgical Pulmonary Embolectomy.

Andexanet alfa neutralizes factor Xa inhibitors in critical bleeding situations. However, in cardiac surgery with cardiopulmonary bypass (CPB), heparin resistance induced by andexanet alfa should be a concern, and the lack of point-of-care monitoring of plasma concentration of factor Xa inhibitors makes it difficult to decide when to administer andexanet alfa. A 69-year-old man underwent emergency surgery for acute pulmonary thromboembolism. The patient had been on edoxaban until the day before the surgery. Withdrawal from CPB required venoarterial extracorporeal membrane oxygenation due to right heart failure, followed by severe bleeding that required massive transfusion. Despite adequate coagulation factor replacement, bleeding persisted and citrated kaolin-reaction time (CK-R) on thromboelastography (TEG) was prolonged. Administering andexanet alfa achieved excellent hemostasis without any thrombosis and normalized the prolonged CK-R of TEG. This is the first report of a change in TEG findings before and after administration of andexanet alfa in a cardiac surgery patient taking factor Xa inhibitor. Monitoring CK-R in TEG may help evaluate the anticoagulant effect of factor Xa inhibitors and the reversal effect of andexanet alfa.

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.

Risk Factors of Ischemic Stroke in Patients With Atrial Fibrillation After Transcatheter Aortic Valve Implantation from the Randomized ENVISAGE-TAVI AF Trial.

In patients with prevalent or incident atrial fibrillation (AF) after successful transcatheter aortic valve implantation (TAVI) enrolled in the EdoxabaN Versus standard of care and theIr effectS on clinical outcomes in pAtients havinG undergonE Transcatheter Aortic Valve Implantation - in Atrial Fibrillation (ENVISAGE-TAVI AF) trial, the incidence of ischemic stroke (IS) and any stroke was numerically less in the edoxaban group than in the vitamin K antagonist (VKA) group. The present study aimed to identify risk factors associated with IS in an on-treatment subanalysis in patients from ENVISAGE-TAVI AF who received ≥1 dose of edoxaban or VKA. Baseline patient characteristics were compared in patients with and those without IS. Numerical variables were compared using a 1-way analysis of variance; categorical variables were compared using Fisher's exact test. Stepwise Cox regression determined patient characteristics associated with the first IS event. Of 1,377 patients, 41 (3.0%) experienced an IS, and 1,336 (97.0%) did not; baseline demographics and clinical characteristics were well balanced between groups. Most ISs occurred within 180 days of TAVI for edoxaban (57.9%) and VKA (68.2%). The rate of IS was 2.0/100 person-years for edoxaban versus 2.7/100 person-years for VKA. Independently associated with IS were history of systemic embolic events (hazard ratio 2.96, 95% confidence interval 1.26 to 7.00, p = 0.01) and pre-TAVI use of VKAs (hazard ratio 2.17, 95% confidence interval 1.12 to 4.20, p = 0.02). In conclusion, although the overall incidence of IS was small for patients with AF on edoxaban or VKA after successful TAVI, patients with a history of systemic embolic events or pre-TAVI use of VKAs may be at greater risk of IS after TAVI.

Edoxaban enfolded beta-1,4-poly-d-glucosamine nanoparticles for targeting eponym 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 (RSM). ETM-loaded CS nanoparticles (ETM-CS-NPs) were developed using the ionic gelation of CS with tripolyphosphate (TPP). Utilising 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 infra-red spectroscopy. The response surface approach and Design-Expert software optimised the ETM-CS-NPs. Using RSM, 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 analysed. 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 optimised 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.

Clinical trial evaluation: the EDOSURE clinical trial program.

EDOSURE is a trial program of the direct oral anticoagulant drug edoxaban, comprising ten randomized clinical trials of which eight are currently published. They evaluate the use of edoxaban in the treatment of nonvalvular atrial fibrillation and acute venous thromboembolism, including in special circumstances such as patients undergoing cardiac procedures, cancer-associated venous thromboembolism, and elderly patients whose bleeding risk precludes conventional anticoagulation strategies. As a result of the collective evidence generated by EDOSURE, edoxaban is now recommended as a treatment option by numerous international guidelines. This review summarizes the context, rationale, and key findings of the studies.

EDOSURE is a collection of clinical trials of the medication edoxaban ­ a blood thinner used to treat or prevent clotting. It encompasses ten trials, eight of which are complete and two are ongoing. Edoxaban's main uses are in patients with atrial fibrillation, or venous clots (e.g., deep vein thrombosis). Trials of blood thinners need to assess the balance of effectiveness (how well the drug treats or prevents clotting) against risk (causing bleeding). These trials collectively demonstrate first that edoxaban is an effective treatment in these conditions and is at least as safe as traditional options like warfarin. Second, in patients with atrial fibrillation who are undergoing procedures like cardiac stenting or ablations, edoxaban is as effective as the previous standard treatments. Finally, in higher-risk populations, such as frail and/or elderly patients, edoxaban can represent a relatively safe option at lower doses. This article is a review of the individual trials, their important findings, and potential limiting factors.

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.

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.

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

Clinical trial registration number: NCT02950168, NCT02951039.

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.

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.