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AIM: The 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation. METHODS: A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation and the 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.

ABSTRACT Aims Methods Results Conclusions Budd‐Chiari syndrome (BCS) is managed by interventions aimed at relieving hepatic venous obstruction and anticoagulation. Despite robust data supporting the tolerability and efficacy of direct oral anticoagulants (DOACs) in patients with other venous thromboembolism, its utility in BCS is not well documented. This study aims to evaluate the efficacy and tolerability of DOACs in Primary BCS from the available literature.Published studies that reported data on patients with BCS treated with DOACs were included.Two retrospective studies and nine case reports met the criteria for inclusion. The combined data from these two retrospective studies include 58 patients administered DOAC and 101 patients treated with VKA/LMWH. The combined re‐stenosis or failure rates after percutaneous endovascular intervention, angioplasty, TIPS, or OLT were 17.2% for the DOAC group and 15.8% for the LMWH/VKA group. The incidence of major bleeding was 8.62% in the DOAC group and 5.94% in the LMWH/VKA group, while minor bleeding rates were 20.7% and 4.95%, respectively. Procedure‐related bleeding was 4.5% in DOAC group and 12.8% in VKA/LMWH group. Nine case reports using apixaban in 3, rivaroxaban in 5, and one with dabigatran‐ described patients tolerating the treatment well and experiencing no major adverse events.DOACs appear to be at least equally effective to LMWH/VKA for the anticoagulation of patients with BCS. We believe DOACs to be preferred over LMWH/VKA for the anticoagulation of patients with BCS due to the known advantages in administration, but randomized trials might be needed to answer this question. [ABSTRACT FROM AUTHOR]

BACKGROUND: Despite consistent recommendations from Clinical guidelines, data from random-deized trials on a Iong-term antithrombotic treatment strategy for patients with atrial fibrillation and stable coronary artery disease are still lacking. METHODS: We conducted a multicenter, open-label, adjudicator-masked, randomized trial com-paring edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus Songpasingle antiplatelet agent) in patients with atrial fibrillation and stable coronary artery disease (defined as coronary artery disease previously treated with revascularization or Divimanaged medically). The risk of stroke was assessed on the basis of the CHA2DS~VASC score (scores range from 0 to 9, with higher scores indicating a greater risk of stroke). The primary outcome was a composite ofdeath from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major bleeding or clinically relevant nonmajor bleeding at 12 months. Secondary outcomes included Supplea composite of major ischemic events and the safety outcome of rnajor bleeding or clinically relevant nonmajor bleeding. RESULTS RESULTS: We assigned 524 patients to the edoxaban monotherapy group and 516 patients to the dual antithrombotic therapy group at 18 sites in South Korea. The mean age of the patients was 72.1 years, 22.9% were women, and the mean CHA2DS2-VASc score was 4.3. At 12 months, a primary-outcome event had occurred in 34 patients (Kaplan-Meier estimate, 6.890) assigned to edoxaban monotherapy and in 79 patients (16.2°6) assigned to dual antithrombotic therapy (hazard ratio, 0.44; 95% confidence interval [CI], 0.30 to 0.65; P<0.001). The cumulative incidence of major ischemic events at 12 months appeared to be similar in the trial groups. Major bleeding or clinically relevant nonmajor bleeding occurred in 23 patients (Kaplan-Meier estimate, 4.70) in the edoxaban monotherapy group and in 70 patients (14.2°/0) in the dual antithrombotic therapy group (hazard ratio, 0.34; 95% CI, 0.22 to 0.53). CONCLUSIONS: In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy led to a lower risk ofa composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding at 12 months than dual antithrombotic therapy. (Funded by the CardioVascular Research Foundation and others; EPIC-CAD ClinicalTrials.gov number, NCT03718559. [ABSTRACT FROM AUTHOR]

We investigated bleeding complications in patients admitted to the emergency department (ED) who were taking oral anticoagulants and compared the rates of major and minor bleeding events between the direct oral anticoagulant (DOAC) and warfarin groups. We conducted a prospective, multicenter observational study of warfarinand DOAC-treated patients who presented to the EDs of tertiary-care hospitals between July 2020 and July 2021 with a bleeding event. Among 518 patients on anticoagulation therapy, 121 (23.4%) presented to EDs with bleeding events. A chart review revealed 73 (60.24%) patients with bleeding events who were taking a DOAC (i.e., apixaban, edoxaban, rivaroxaban, or dabigatran) and 48 who were taking warfarin. The rate of bleeding events was significantly higher among patients treated with warfarin than among those treated with DOACs (48/129 [37.2%] vs. 73/389 [18.8%], p<0,001). Subgroup analysis of the DOAC-treated patients revealed a significant difference in the frequency of bleeding events among the DOAC groups (p=0.016), with a significantly lower frequency in patients treated with rivaroxaban versus edoxaban (14.9% vs. 34.7%, p=0.002) and in those treated with apixaban versus edoxaban (18.8% vs. 34.7%, p=0.021). Our findings indicate that although the rates of overall bleeding events differed among DOAC-treated patients, the rates of bleeding events were lower than those in warfarin-treated patients. Additionally, major bleeding events occurred less frequently in patients treated with rivaroxaban or apixaban compared with edoxaban. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the pharmacokinetic (PK) interactions between clarithromycin (a P-glycoprotein [P-gp] inhibitor) and four direct oral anticoagulants (DOACs) (P-gp substrates) using physiologically based PK (PBPK) models to elucidate the influence of P-gp in the interaction between them. Methods: PBPK models for clarithromycin, DABE–dabigatran (DAB), rivaroxaban, apixaban, and edoxaban were constructed using GastroPlus™ (version 9.9), based on physicochemical data and PK parameters from the literature. The models were optimized and validated in healthy subjects. We evaluated the predictive performance of the established model and further assessed the impact of P-gp on the PK of the four DOACs. Successfully validated models were then used to evaluate potential drug–drug interactions (DDIs) between clarithromycin and the DOACs. Results: The established PBPK models accurately described the PK of clarithromycin, DABE–DAB, rivaroxaban, apixaban, and edoxaban. The predicted PK parameters (Cmax, Tmax, AUC0-t) were within 0.5–2 times the observed values. A sensitivity analysis of P-gp parameters indicated that an increase in P-gp expression was reduced by in vivo exposure to DOACs. The models demonstrated good predictive ability for DDIs between clarithromycin and the anticoagulants, and the ratio of the predicted values to the observed values of Cmax and the area under the curve (AUC) in the DDI state was within the range of 0.5–2. Conclusions: Comprehensive PBPK models for clarithromycin, DABE–DAB, rivaroxaban, apixaban, and edoxaban were developed, which can effectively predict DDIs mediated by P-gp's function. These models provide theoretical support for clinical dose adjustments and serve as a foundation for future PBPK model development for DOACs under specific pathological conditions. [ABSTRACT FROM AUTHOR]

Background: The therapeutic effects of oral anticoagulant drugs for nonvalvular atrial fibrillation (NVAF) suggest that the three factor Xa (FXa) inhibitors may have distinct safety profiles, though this is not yet fully conclusive. This study investigated the current dosing of rivaroxaban, apixaban, and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity from the viewpoint of the safety. Methods and results: This multicenter clinical study monitored the drug PC and two coagulation biomarkers (fibrinogen and fibrin monomer complex [FMC]) at peak and trough timing in 268 outpatients taking rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted based on the dose-adjustment criteria of each drug. Referencing our previous study, peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (rivaroxaban, n = 3; apixaban, n = 2; edoxaban, n = 3) in whom bleeding events occurred. Among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels, reflecting thrombin activity, remained within the normal range (<6.1 µg/mL) regardless of PC variations. These results indicated that the anticoagulant effects of these drugs persisted throughout the day regardless of the drug PC levels, dosage, and dosing frequency. Regarding the change over time in peak PC, the elevation over time developed more in rivaroxaban (29/57; 50.9%, p < 0.05) than in edoxaban (32/101; 31.7%), and rivaroxaban tended to accumulate more than edoxaban. Conclusions: Although drug PC levels of once-daily FXa inhibitors widely varied from peak to trough, FMC levels were maintained within the normal range without daily variations. Rivaroxaban also tended to accumulate over time. The results indicate the low risk of thrombotic events with once-daily FXa inhibitors and its correspondence to the twice-daily regimen. [ABSTRACT FROM AUTHOR]

Background/Objectives: The practice of holding anticoagulation is a relatively common approach, with the aim of either preventing excessive bleeding in preparation for surgical procedures or managing acute bleeding episodes. Methods: To assess the relationship between the discontinuation of direct oral anticoagulants (DOACs) therapy and the condition of hypercoagulability, a systematic review of the literature was conducted, following PRISMA guidelines, in PubMed/MEDLINE, Cochrane, and Google Scholar. These databases were searched for all publications that described a rebound phenomenon or hypercoagulability state after DOACs discontinuation. Results: A total of 1494 articles were selected from searched databases, and 29 were eligible. A final total of 16 case reports and 14 original research articles were subjected to analysis. Conclusions: The results of this study indicate that the cessation of DOAC therapy may be associated with an increased risk of thrombotic events. More studies are required to ascertain whether DOACs treatment cessation can be linked to rebound phenomena associated with thromboembolic events. This will provide the data needed to determine the incidence and risk of this phenomenon. [ABSTRACT FROM AUTHOR]

Background: Although there are reports on the recurrence prevention in the chronic phase using direct oral anticoagulants (DOACs) for deep vein thrombosis (DVT) in patients with cancer, acute thrombus regression effect using DOACs has not been assessed. This study aimed to assess the thrombus regression effect of initial treatment using edoxaban for acute lower-extremity DVT in patients with active cancer. Methods and Results: In this observational study, among the inpatients with cancer and lower-extremity DVT who underwent initial treatment with edoxaban at our hospital from November 2019 to December 2021, 34 consenting patients were recruited in this study. The quantitative ultrasound thrombus (QUT) score of thrombus volume was calculated at baseline (before administration) and 7–14 days after the start of edoxaban administration, using lower-extremity venous ultrasound to evaluate changes in thrombus volume. The primary and secondary endpoints were the acute thrombus regression effect of edoxaban and the impact of patients' clinical frailty on the thrombus regression effect, respectively. Anticoagulant therapy with edoxaban significantly reduced QUT score (p < 0.001). In addition, regardless of the Clinical Frailty Scale scores, QUT score decreased significantly. Conclusion: Initial treatment with edoxaban was effective for lower-extremity DVT in patients with cancer. In addition, the effect was the same independent of the degree of frailty. [ABSTRACT FROM AUTHOR]

Background: Edoxaban, the only factor Xa inhibitor with active metabolites, is metabolized by carboxylesterase-1 to its main active metabolite, M-4, which is a substrate of organic anion transporting polypeptide 1B1 (OATP1B1) and is excreted in bile and urine. Because the area under the plasma concentration–time curve ratio of M-4 to parent compound is typically less than 10% in healthy subjects, M-4 is generally considered to exhibit negligible antithrombotic activity in patients treated with edoxaban. However, we identified a case in which drug interactions and kidney impairment led to a substantive increase in plasma M-4 concentrations. Case presentation: This case report involved a 68-year-old man with pancreatic cancer who was orally administered edoxaban tablets for prevention of thrombus formation in non-valvular atrial fibrillation, in addition to rifampin and clarithromycin (CAM) for treatment of mycobacterium avium complex lung disease. These medications were temporarily discontinued for a pancreaticoduodenectomy but were resumed 8 days post-surgery (POD8). On POD9, the patient developed acute kidney injury, and the trough concentrations of edoxaban and M-4 were 131.1 ng/mL and 115.8 ng/mL, respectively (M-4 ratio: 88.3%). On POD11, the M-4 trough concentration and M-4 ratio increased to 216.2 ng/mL and 186.2%, respectively. The plasma concentration of coproporphyrin-I, an endogenous biomarker of OATP1B1 activity, increased during this period. Conclusions: This case suggests that in patients with impaired renal function taking edoxaban, co-administration of carboxylesterase-1 inducers such as rifampin and/or OATP1B1 inhibitors such as rifampin or clarithromycin may increase plasma concentrations of M-4 to clinically non-negligible levels. [ABSTRACT FROM AUTHOR]

Background: To evaluate the clearance of edoxaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. Methods: Edoxaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of edoxaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for edoxaban were estimated via noncompartmental analysis. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLCRRT. Linear regression was utilized to provide dosing estimations across CRRT effluent flow rates from 0.5 to 5 L/h. Optimal edoxaban doses were suggested using CLCRRT and population non-renal clearance (CLNR) to estimate total clearance and match the systemic AUC associated with efficacy in the treatment of venous thromboembolism. Results: Edoxaban clearance from the CRRT circuit occurred primarily via hemofilter adsorption to the HF1400 and M150 filters at 74% and 65%, respectively, while mean percent protein binding was 41%. Multivariate analyses confirmed the lack of influence of CRRT mode, filter type, and point of dilution on the CLCRRT of edoxaban allowing dosing recommendations to be made based on effluent flow rate. Edoxaban doses of 30-45 mg once daily were estimated to achieve target the AUC threshold for flow rates from 0.5 to 5 L/h. Conclusion: For CRRT flow rates most employed in clinical practice, an edoxaban dose of 45 mg once daily is predicted to achieve target systemic exposure thresholds for venous thromboembolism treatment. The safety and efficacy of this proposed dosing warrants further investigation in clinical studies. [ABSTRACT FROM AUTHOR]

Background: Vitamin‐K antagonists (VKAs) have widely been replaced by non‐VKA oral anticoagulants (NOACs). This includes Austria, Germany and Switzerland, where as VKA, instead of warfarin, the much longer‐acting phenprocoumon is used, which was not compared to NOACs in clinical trials. Methods: Using administrative data from a large German health insurance, we included all anticoagulation‐naïve patients with a first prescription of a NOAC or VKA between 2012 and 2020. We analysed overall survival, major adverse cardiac and cerebrovascular events, major thromboembolic events and major bleeding. Results: Overall, 570,137 patients were included (apixaban: 26.9%, dabigatran: 4.6%, edoxaban: 8.8%, rivaroxaban: 39.1% and VKA: 20.7% of these 99.4% phenprocoumon). In the primary analysis using a 1:1 propensity score matching‐cohort (PSM‐cohort), a significantly higher overall mortality was found for apixaban, edoxaban and rivaroxaban (all p < 0.001) but not for dabigatran (p = 0.13) compared to VKA. In this PSM‐cohort, 5‐year mortality was 22.7% for apixaban versus 12.7% for VKA, 19.5% for edoxaban versus 11.4% for VKA, 16.0% for rivaroxaban versus 12.3% for VKA (all p < 0.001) and 13.0% for dabigatran versus 12.8% for VKA (p = 0.06). The observed effect was confirmed in sensitivity analyses using un‐weighted and three different weighted Fine–Gray regression models on the basis of the entire cohort. Conclusions: In this large real‐world analysis, apixaban, edoxaban and rivaroxaban, but not dabigatran, were associated with worse survival compared to VKA. These findings, consistent with a few other studies including phenprocoumon, cast profound doubts on the unreflected, general use of NOACs. Randomized trials should assess whether phenprocoumon might actually be superior to NOACs. [ABSTRACT FROM AUTHOR]

Purpose: To report an incident of a breakthrough deep vein thrombosis (DVT) and potential example of a drug-drug interaction in a patient treated with edoxaban and rifabutin who was being treated for respiratory tuberculosis. Case: A 76-year-old male presented with anemia requiring transfusion and subsequent shortness of breath that was later diagnosed to be respiratory tuberculosis. He experienced a prolonged hospital stay due to persistently positive Mycobacterium tuberculosis respiratory samples and a complicated social situation that required continuous hospitalization for approximately five months. During his treatment the patient was transitioned from apixaban to edoxaban due to a drug-drug interaction with rifabutin. He subsequently had a DVT while on edoxaban after two months of therapy that would require him to transition to warfarin. Conclusion: This case represents an example of a potentially significant drug-drug interaction between edoxaban and rifabutin. Other direct oral anticoagulants (DOACs) exhibit a potential drug-drug interaction that limit their effectiveness when used with rifamycins. This report describes the first known case of a patient experiencing a DVT after prolonged edoxaban use in combination with rifabutin. Treatment with DOACs for patients taking concomitant cytochrome P450 (CYP) inducers such as rifabutin may be more complicated than previously believed. [ABSTRACT FROM AUTHOR]

Background: The distribution of anti‐factor Xa activity (AXA) in patients with nonvalvular atrial fibrillation (NVAF) taking edoxaban 15 mg has not been fully elucidated. Methods and Results: The trough and peak AXA were measured in 19 NVAF patients taking edoxaban 15 mg. We compared these results with those in patients taking edoxaban 30 mg. The peak AXA differed significantly between the 15 mg and the 30 mg groups (0.74 ± 0.40 IU/mL vs. 1.25 ± 0.48 IU/mL, respectively; p < 0.0001). Conclusions: Peak but trough AXA in the patients receiving edoxaban 15 mg were significantly lower than those in patients receiving edoxaban 30 mg. [ABSTRACT FROM AUTHOR]

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Abstract Background Edoxaban, the only factor Xa inhibitor with active metabolites, is metabolized by carboxylesterase-1 to its main active metabolite, M-4, which is a substrate of organic anion transporting polypeptide 1B1 (OATP1B1) and is excreted in bile and urine. Because the area under the plasma concentration–time curve ratio of M-4 to parent compound is typically less than 10% in healthy subjects, M-4 is generally considered to exhibit negligible antithrombotic activity in patients treated with edoxaban. However, we identified a case in which drug interactions and kidney impairment led to a substantive increase in plasma M-4 concentrations. Case presentation This case report involved a 68-year-old man with pancreatic cancer who was orally administered edoxaban tablets for prevention of thrombus formation in non-valvular atrial fibrillation, in addition to rifampin and clarithromycin (CAM) for treatment of mycobacterium avium complex lung disease. These medications were temporarily discontinued for a pancreaticoduodenectomy but were resumed 8 days post-surgery (POD8). On POD9, the patient developed acute kidney injury, and the trough concentrations of edoxaban and M-4 were 131.1 ng/mL and 115.8 ng/mL, respectively (M-4 ratio: 88.3%). On POD11, the M-4 trough concentration and M-4 ratio increased to 216.2 ng/mL and 186.2%, respectively. The plasma concentration of coproporphyrin-I, an endogenous biomarker of OATP1B1 activity, increased during this period. Conclusions This case suggests that in patients with impaired renal function taking edoxaban, co-administration of carboxylesterase-1 inducers such as rifampin and/or OATP1B1 inhibitors such as rifampin or clarithromycin may increase plasma concentrations of M-4 to clinically non-negligible levels.

Abstract Background The distribution of anti‐factor Xa activity (AXA) in patients with nonvalvular atrial fibrillation (NVAF) taking edoxaban 15 mg has not been fully elucidated. Methods and Results The trough and peak AXA were measured in 19 NVAF patients taking edoxaban 15 mg. We compared these results with those in patients taking edoxaban 30 mg. The peak AXA differed significantly between the 15 mg and the 30 mg groups (0.74 ± 0.40 IU/mL vs. 1.25 ± 0.48 IU/mL, respectively; p

Abstract Background To evaluate the clearance of edoxaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. Methods Edoxaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of edoxaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for edoxaban were estimated via noncompartmental analysis. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLCRRT. Linear regression was utilized to provide dosing estimations across CRRT effluent flow rates from 0.5 to 5 L/h. Optimal edoxaban doses were suggested using CLCRRT and population non-renal clearance (CLNR) to estimate total clearance and match the systemic AUC associated with efficacy in the treatment of venous thromboembolism. Results Edoxaban clearance from the CRRT circuit occurred primarily via hemofilter adsorption to the HF1400 and M150 filters at 74% and 65%, respectively, while mean percent protein binding was 41%. Multivariate analyses confirmed the lack of influence of CRRT mode, filter type, and point of dilution on the CLCRRT of edoxaban allowing dosing recommendations to be made based on effluent flow rate. Edoxaban doses of 30-45 mg once daily were estimated to achieve target the AUC threshold for flow rates from 0.5 to 5 L/h. Conclusion For CRRT flow rates most employed in clinical practice, an edoxaban dose of 45 mg once daily is predicted to achieve target systemic exposure thresholds for venous thromboembolism treatment. The safety and efficacy of this proposed dosing warrants further investigation in clinical studies.

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.

The aim of the present study was to assess the occurrence of intra-, peri-, and post-operative bleeding following tooth extractions in patients treated with direct oral anticoagulants (DOACs). Consecutive patients requiring at least one dental extraction were enrolled. The DOAC regimen was either maintained or suspended. Patients were classified in subgroups depending on the number of teeth extracted per procedure (≤3 or >3), the need for flap elevation, and the performance of osteotomy. Bleeding was recorded intra-operatively; peri-operatively at 20, 40, 60, and 80 min after the procedure; and daily in the first seven days following tooth extractions. Forty-nine patients treated with DOACs (17 with rivaroxaban, 16 with apixaban, 8 with edoxaban, and 8 with dabigatran) were enrolled. Of them, 33 refrained from DOAC administration pre-operatively. The performances of >3 teeth extractions, flap elevation, and osteotomy were significantly associated with higher bleeding rates (p < 0.05). In patients treated with rivaroxaban and apixaban, bleeding episodes were more frequent. Although DOAC treatment may increase the rates of intra-operative, peri-operative, and post-operative bleeding, the recorded episodes were mild and manageable. DOAC suspension may reduce peri-operative bleeding, while no effect could be observed for post-operative bleeding. [ABSTRACT FROM AUTHOR]

Background: The first purpose of this study was to determine whether a measurement of the level of direct oral anticoagulants (DOACs) was possible with heparin-calibrated chromogenic anti-factor Xa activity (AXA). The second purpose of this study was to evaluate whether the antidote treatment decision level (30 or 50 ng/mL of DOAC) can be determined by unfractionated heparin (UHF)/low molecular weight heparin (LMWH)-calibrated AXA. Methods: AXA was measured by using two reagents and dedicated analyzers (Sysmex CS-5100 analyzer and STA R Max3). Four types of calibrators were used: 1) Stago DOAC (rivaroxaban, edoxaban, and apixaban)-specific calibrator, 2) Stago LMWH calibrator, 3) Sysmex UHF calibrator, and 4) Sysmex LMWH calibrator. Regression analysis was used between assays. Receiver operating characteristic (ROC) curves were performed, and the concordance rate was calculated. Results: The correlation coefficients were in the range of 0.75 - 0.91 for rivaroxaban and 0.81 - 0.94 for apixaban. The correlation coefficient between edoxaban-calibrated AXA and Sysmex LMWH/Sysmex UHF calibrator-calibrated AXA was low (r = 0.47). Overall correlation between DOAC-calibrated AXA and Stago LMWH-calibrated AXA was linear, at only low concentration in all three DOACs. The concordance rate (89.3 - 100%) is good for determining the antidote management level by UFH/LMWH-calibrated AXA, compared with those of DOAC-calibrated AXA in rivaroxaban and apixaban. The concordance rate ranged from 63% to 67% between Sysmex UFH/LMWH-calibrated AXA and edoxaban-calibrated AXA. Conclusions: The findings of our study suggest limitations in calculating accurate concentrations, when using UFH/LMWH-calibrated AXA to measure DOAC. This study demonstrates that UFH/LMWH-calibrated AXA may be useful in determining the presence of DOACs at the cutoff level for the antidote treatment in rivarovaban and apixaban. However, in edoxaban, UFH/LMWH-calibrated AXA could not accurately measure the presence of DOACs at the cutoff for antidote treatment. [ABSTRACT FROM AUTHOR]