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Over the past 20 years, there has been a shift from vitamin K antagonists to direct oral anticoagulants (DOACs), which include the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban. Although DOACs are associated with less serious bleeding than vitamin K antagonists, bleeding still occurs with DOACs, particularly in the elderly and in those with comorbidities. Reversal of the anticoagulant effects of the DOACs may be needed in patients with serious bleeding and in those requiring urgent surgery or intervention. Reversal can be effected with specific agents, such as idarucizumab for dabigatran and andexanet alfa for apixaban, edoxaban, and rivaroxaban, or with non-specific agents, such as prothrombin complex concentrates, activated prothrombin complex concentrate, and recombinant activated factor VII. This paper (i) provides an update on when and how to reverse the DOACs, (ii) describes new reversal agents under development, and (iii) provides a strategic framework for the reversal of the factor XI inhibitors currently under investigation in phase three clinical trials., Competing Interests: Conflict of interest J.W. has received grant funding from the Canadian Institutes of Health Research. He is a consultant for and received honoraria from Bayer, Alnylam, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Ionis, Janssen, Merck, Novartis, Pfizer, Regeneron, and Servier. N.v.E has received grant funding from the Dutch Thrombosis Foundation. He has received honoraria from Boehringer Ingelheim. R.d.C. is a consultant for and received honoraria from Bayer, Janssen–BMS, BMS–Pfizer Alliance, Daiichi-Sankyo, Menarini, Milestone, Portola, Guidotti, Novartis, Merck, Roche, and AstraZeneca. He has participated on the Advisory Board for Janssen–BMS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Direct oral anticoagulants (DOACs) can be involved in clinical relevant drug-drug interactions (DDIs) which may compromise safe and effective use. However, assessing the clinical relevance of DDIs with DOACs and managing these interactions optimally, can be challenging in clinical practice., Aim: To develop a practice-oriented list of potentially clinically relevant DDIs with DOACs with corresponding management plans for which it is important to screen in ambulatory care., Method: The RAND/UCLA appropriateness method was used to develop the DOACs DDI list. In a first step a preliminary list was compiled of potentially clinically relevant DDIs per DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) using five reference sources. Subsequently, a two-step modified Delphi process involving a multidisciplinary panel (n = 10) including both pharmacists and physicians with expertise in all decision-making disciplines involved in care for patients using DOACs and with diversity of practice setting, was used to reach expert agreement on a final list of DDIs with corresponding management plans., Results: After a two-step consensus round, 71 DDIs for 20 different interacting drugs were included: five pharmacodynamic, nine pharmacokinetic inhibitor and six pharmacokinetic inducer interacting drugs. Considerations raised and discussed by the panellists were related to (1) the necessity of the interacting drug, (2) the manageability of the DDI (whether there are any alternatives), (3) the (clinical) evidence-base for the DDI and (4) the (potential) consequences of the DDI., Conclusion: We developed a consensus list with specific and straightforward management plans on potentially clinically relevant DDIs with DOACs, for use in ambulatory care., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background There is evidence that direct oral anticoagulants administered as potentially inappropriate medications increase the risk of bleeding and thromboembolic complications, which represent serious threats to human health. Objective To identify direct oral anticoagulants administered as potentially inappropriate medications for hospitalized patients aged ≥ 65 years in our hospital, and to determine associated factors and the correlation between potentially inappropriate medications and adverse reactions. Setting Xi'an Central Hospital, China. Method A retrospective cross-sectional study of elderly hospitalized patients who received either dabigatran or rivaroxaban at Xi'an Central Hospital between June 1, 2018 and June 1, 2019. The evaluation criteria of direct oral anticoagulants were formulated based on drug labels, disease guidelines and the 2019 American Geriatrics Society Beers Criteria, and any non-compliance with the criteria was considered to be potentially inappropriate medications. The Pearson chi-square test and a binary logistic regression model were used. Main outcome measure Factors associated with potentially inappropriate medications and correlation between potentially inappropriate medications and adverse reactions. Results This study analysed 315 patients aged ≥ 65 years. The application of our evaluation criteria identified 155 (49.2%) instances of potentially inappropriate medications, comprising 5 different types of potentially inappropriate medications. Fifteen adverse drug reactions occurred in the study participants. The Pearson chi-square test revealed significant differences in number of medications (p = 0.021) and creatinine clearance rate (p = 0.002) between potentially inappropriate medications and non-potentially inappropriate medications groups. In the binary logistic regression model, potentially inappropriate medications use was associated with creatinine clearance (creatinine clearance < 30: OR = 3.590, 95% CI = 1.214-10.615, p = 0.021), and there was no significant correlation between potentially inappropriate medications and adverse drug reactions after eliminating the confounding factors (age, length of hospitalization, number of disease combined) with p values of less than 0.25 (adjusted OR = 0.372, 95% CI = 0.117-1.182, p = 0.094). Conclusion This study revealed that the incidence of potentially inappropriate medications was relatively high, number of medications and creatinine clearance differed significantly between potentially inappropriate medications and non-potentially inappropriate medications groups, and potentially inappropriate medications was associated with creatinine clearance (creatinine clearance < 30 mL/min), but there was no significant correlation between potentially inappropriate medications and adverse drug reactions after eliminating the confounding factors.

Antiplatelet agents and vitamin K antagonists (VKA) are usually used in the treatment of cervical (carotid or vertebral) artery dissections (CADs); however, data about the use of direct oral anticoagulants (DOACs) in these conditions are very limited. DOACs have proven to be effective in stroke reduction in non-valvular atrial fibrillation and, when possible, they are preferred to warfarin because of their better safety profile. We describe four cases of CADs and, firstly in literature, cervico-cerebral (CCADs) in young patients (average age of 42 years) treated with rivaroxaban 20 mg daily. Three of these four dissections had affected the vertebral artery (condition with an unfavorable prognosis and more often complicated by subarachnoid hemorrhages), and the other one was a carotid dissection at the extra-intracranial passage. All patients were followed clinically and with serial neurosonological examinations at 1, 3, and 6 months and with magnetic resonance angiography (MRA) at 6 months. All patients presented a good outcome with vascular recanalization without stroke recurrence or bleedings, even in patients with intracranial vertebral artery involvement. DOACs could be an alternative in young patients with CADs and their use could be considered in intracranial artery dissections too.

Essentials Direct oral anticoagulants (DOAC) are used for stroke and venous thromboembolism prevention. We report a new assay that measures anti-factor Xa DOAC levels in plasma and whole blood. Rivaroxaban and apixaban can be accurately quantified below trough levels. The ease and accuracy of the assay demonstrate its potential for point-of-care applications., Background: Rivaroxaban and apixaban are the most commonly used anti-factor (F) Xa direct oral anticoagulants (DOAC), with indications for prevention of stroke in nonvalvular atrial fibrillation as well as treatment and prevention of venous thromboembolism. However, lacking is accessibility to a detection method that is able to quantify low levels of anti-FXa DOACs., Objective: We report a new assay that measures anti-FXa DOAC levels in plasma and whole blood., Methods: This is achieved by the use of a prothrombin derivative that is labeled with a fluorescent probe (Flu-II), which then acts as the macromolecular substrate to measure residual FXa activity. The Flu-II cleavage is then initiated by the addition of a solution containing FXa, FVa, and phospholipid vesicles composed of 75% PC and 25% PS (PCPS) vesicles with calcium, in the presence of hirudin to prevent feedback activity by the native thrombin generated. The Flu-II cleavage is monitored by fluorescence in real time where the initial rate of fluorescence change is inversely proportional to DOAC levels., Results: In plasma systems, the assay demonstrates dose-response between 0 and 5 nmol/L rivaroxaban and between 0 and 10 nmol/L apixaban. Corn trypsin inhibitor did not affect this assay. With individual plasma samples, the assay showed excellent consistency and reproducibility. From 2 μL of whole blood, the assay showed dose-response between 0 and 2 nmol/L of DOACs in the final mixture of 100 μL, thus representing up to 100 nmol/L in circulating blood., Conclusion: The assay is ideal for rapidly and accurately measuring DOAC levels in plasma and blood, demonstrating its potential for point-of-care applications., (© 2019 International Society on Thrombosis and Haemostasis.)

There is limited clinical experience with the use of coagulation concentrates to reverse the effect of direct oral anticoagulants. We assess the achievement of effective clinical hemostasis with the use of 4-factor prothrombin complex concentrate (PCC) in patients on apixaban or rivaroxaban presenting with major bleeding. A retrospective chart review was conducted at a tertiary referral medical center in the USA. We assess the achievement of clinical hemostasis using 4-factor PCC in patients on chronic apixaban or rivaroxaban therapy presenting with major bleeding. Clinical hemostasis was assessed by the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria. A total of 29 patients are included in the study. The most common site of bleeding was intracranial hemorrhage (ICH) (72.4%), followed by gastrointestinal bleed (13.8%). Clinical hemostasis was achieved in 21 (72.4%) patients. Patients who did not achieve clinical hemostasis (27.6%) suffered from ICH, and all of them died during hospitalization except for two patients who were discharged with neurologic deterioration. One patient developed multiple brain infarctions after receiving 4-factor PCC. Sixteen patients (55.2%) were receiving concomitant medications that interact with apixaban and rivaroxaban and increase the risk of bleeding. Four-factor PCC appears to be effective in achieving clinical hemostasis in patients on apixaban or rivaroxaban presenting with major bleeding. It may be an alternative to patients who need anticoagulation reversal if the specific antidote, andexanet alfa, is not available.

The availability of direct oral anticoagulants has caused a paradigm shift in the management of thrombosis. Rivaroxaban and apixaban are 2 direct oral anticoagulants whose target specificity is activated factor X (FXa). However, it is still not fully understood if and how xabans impact platelet function. This observational study aimed to assess the in vitro platelet function in patients with atrial fibrillation receiving xabans. This was a single-center study quantifying platelet aggregation in 41 patients treated with apixaban or rivaroxaban by light transmission aggregometry. The thrombin receptor activating peptide (TRAP)-induced platelet aggregation was significantly lower 2 hours after taking rivaroxaban or apixaban compared to baseline value (56.15% [8.53%] vs 29.51% [12.9%]; P = .000). Moreover, concomitant use of angiotensin-converting enzyme blockers, proton pump inhibitors, and statins reduces the efficiency of xabans. The TRAP-induced platelet aggregation was reduced in patients with cardiovascular disease 2 hours after receiving xabans.

Background: Thromboembolic complications can be life-threatening during atrial fibrillation (AF) catheter ablation. The aim of our study was to evaluate the safety and efficacy of continuous treatment using direct oral anticoagulants (DOACs) as an alternative to uninterrupted acenocoumarol for periprocedural anticoagulation., Hypothesis: Continuous treatment with DOACs has similar safety and efficacy compared to acenocoumarol., Methods: We enrolled 474 patients (mean age, 58 years; 68.4% male) undergoing AF catheter ablation between June 2013 and December 2016. All patients were equally assigned to take acenocoumarol (group 1, 136 patients) or DOACs (group 2, 338 patients) for ≥2 months before the procedure. We compared thromboembolic and bleeding complications between the 2 groups., Results: Our analysis showed no significant difference in major and minor complications between the 2 patient groups. Specifically, 3 of 136 patients (2.2%) using uninterrupted acenocoumarol had a major complication (1 patient [0.7%] had transient ischemic attack resolved 8 hours later, 1 [0.7%] had pericardial tamponade, and 1 [0.7%] had a subcapsular renal hematoma) and 2 patients (1.4%) had minor complications (1 [0.7%] pseudoaneurysm and 1 [0.7%] groin hematoma). In group 2, 1 of 338 patients (0.3%) had a major complication (transient ischemic attack). In the same group, 7 patients (2.1%) had a minor complication (1 patient [0.3%] presented with pseudoaneurysm, 4 [1.2%] with pericardial effusion <1 cm, 1 [0.3%] femoral arteriovenous fistula between the femoral artery and femoral vein, and 1 [0.7%] groin hematoma)., Conclusions: DOACs and acenocoumarol have similar safety and effectiveness regarding thromboembolic complications prevention without increasing bleeding complications., (© 2017 Wiley Periodicals, Inc.)

Purpose: Measuring the anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban and rivaroxaban is challenging, since the activated coagulation time (ACT) does not seem to reflect the true anticoagulant activity of these drugs. We therefore evaluated coagulation properties of apixaban and rivaroxaban during RFA by different coagulation assays to better monitor periprocedural hemostasis., Methods: The study included 90 patients (61 ± 12 years) with atrial fibrillation who underwent RFA procedures. Patients received 20 mg rivaroxaban (n = 73) once or 5 mg apixaban (n = 17) twice daily 4 weeks prior to the procedure. During RFA, unfractionated heparin i.v. was given to maintain an ACT of 250-300 s. Blood samples were taken before and 10, 60, and 360 min after heparin administration., Results: Heparin displayed a lower anti-Xa activity in rivaroxaban-treated patients compared to apixaban-treated patients. In contrast, D-dimer and prothrombin fragment F1+2 plasma levels indicated a higher activation of the coagulation cascade in apixaban/heparin than in rivaroxaban/heparin patients. This discordant coagulative state measured in vitro had no clinical impact in terms of bleeding or thromboembolic complications., Conclusion: We found different biochemical responses to rivaroxaban/heparin and apixaban/heparin during RFA. Precaution is necessary when monitoring periprocedural hemostasis in DOAC patients to avoid mismanagement.

Purpose: Direct factor Xa inhibitors such as rivaroxaban or apixaban may prolong prothrombin time (PT) and elevate international normalized ratio (INR). However, these tests are not reliable for assessing the anticoagulation effects of these agents. PT assay sensitivity is relatively weak at therapeutic drug concentrations and is subjected to significant variations depending on the reagent used. Conversion of PT to INR may even increase the variability. We conducted a retrospective cross-sectional study aiming to assess the prevalence and extent of INR elevation in hospitalized patients receiving rivaroxaban or apixaban as part of their home medications and to find out whether other existing factors could elevate INR apart from the drug entity itself., Methods: The data collected from 218 hospitalized patients׳ charts included PT and INR taken on admission, patients׳ characteristics, laboratory results, other medications regularly used, and coexisting clinical conditions., Findings: No statistically significant association between INR elevation and the parameters examined was found in our study. INR was significantly elevated in both drug groups (P < 0.001), with 84.2% of rivaroxaban patients and 78.3% of apixaban patients presenting with INR levels above the higher limit of the normal range. Furthermore, INR was significantly higher in the rivaroxaban group than in the apixaban group (P < 0.001)., Implications: Both of the reviewed drugs significantly elevated INR. Moreover, rivaroxaban elevates INR significantly more than apixaban, and there are apparently no other factors affecting INR but the drugs themselves. Larger prospective studies are needed to confirm and clarify the clinical significance of these results., (Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.)

Backgound: Randomized controlled trials (RCTs) have shown that dabigatran, rivaroxaban and warfarin cause similar bleeding rates., Methods: We performed a retrospective population-based cohort study to determine the incidence of bleeding in patients with atrial fibrillation (AF) beginning dabigatran, rivaroxaban or warfarin. Consecutive patients initiating anticoagulation for AF during a 3year period were identified using a computerized database. Patients who bled and required hospitalization underwent chart review. Bleeding incidences were calculated per 100 patient-years of treatment., Results: 18,249 patients were included: 9564 (52.4%) received warfarin, 5976 (32.7%) dabigatran, and 2709 (14.8%) rivaroxaban. Bleeding incidences were 3.9 (95% CI, 3.6-4.4) in warfarin-treated patients, 4.2 (95% CI, 3.7-4.7) in dabigatran patients, and 4.1 (95% CI, 3.0-5.3) in rivaroxaban patients. Intracranial hemorrhage (ICH) rates were 0.71 (95% CI, 0.56-0.90) for warfarin, 0.4 (95% CI, 0.18-0.87) for dabigatran, and 0.27 (95%CI, 0.10-0.80) for rivaroxaban. GI hemorrhage rates were 1.88 (95%CI, 1.62-2.20) for warfarin, 2.98 (95% CI, 2.4-3.5) for dabigatran and 2.39 (95%CI, 1.6-3.5) for rivaroxaban., Conclusions: We demonstrate similar bleeding rates with both dabigatran 150mg and 110mg and rivaroxaban compared to warfarin., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

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]

The aim of the study was to investigate the dynamics of inpatient consumption of direct oral anticoagulants in different regions of the Russian Federation for the period from 2017 to 2022.Materials and methods. This study is a non-interventional, retrospective analysis of the electronic database records of Cursor Marketing LLC (Russia) about the announced by medical organizations and executed contracts for the purchase of direct oral anticoagulants (DOACs). The сonsumption was calculated on the basis of a DDD (defined-daily-dose) and estimated DDDTID (defined-daily-dose/1000-inhabitants/day) for each DOACs: rivaroxaban, dabigatran and apixaban. The Rosstat database available on its official website were used as a source of inhabitants data for the Russian regions.Results. A total of 57 866 records were entered into the analyzed databases of Cursor Marketing LLC (Russia) from 2017 to 2022, 47.38% of which indicated rivaroxaban as the drug being procured, 26.51% indicated dabigatran, and 26.11% indicated apixaban. Edoxaban was not procured by healthcare organizations. During the period investigated, there was an increase in the consumption of all DOACs studied, with a higher increase for apixaban (by an average of 284.6% per year), then rivaroxaban (by 144.8% per year) and, to a lesser extent, dabigatran (by 92.5% per year). The analysis of DOACs consumption in general showed that compared to 2017, the need for these drugs in medical organizations in 2022 increased by 18 times. The Urals Federal District consistently exceeds the national average in terms of DDTID consumption. Noteworthy is the consumption dynamics of the regions of the Central Federal District and the North-Western Federal District, which made it possible to achieve DDDTID values above the national average for 5 out of 6 observation years. The lowest rates of DOACs consumption were observed in the Volga Federal District, which, despite positive growth dynamics, failed to reach the national average values. A high level of consumption (>10 DDDTID) of rivaroxaban was noted for the Arkhangelsk region (2018) and the Nenets Autonomous District (in 2021), dabigatran – only for the Arkhangelsk region (in 2018). Many more regions reached high levels of the apixaban consumption, especially in 2021.Conclusion. Despite a number of limitations, the data on the volume of DOACs procurement can be used in the analysis of the consumption at both regional and national levels. When analyzing the DOACs consumption, the impact of COVID-19 pandemic and pharmacogenetic features of patients in different regions should be taken into account. During the studied period of time, a significant part of the Russian regions achieved a consumption level of rivaroxaban and apixaban, but not dabigatran, exceeding 1 DDDTID.

Abstract A major advancement in the field of medicine has been the introduction and usage of direct oral anticoagulants (DOACs) such as dabigatran (Pradaxa), apixaban (Eliquis), and rivaroxaban (Xarelto). DOACs have been increasing in popularity for mainstay anticoagulation pharmacotherapy and are being preferred by physicians over warfarin due to their rapid onset, fewer drug and food interactions, and lack of frequent blood monitoring. DOACs have been indicated in the management of thromboembolic conditions and have been extensively researched in various medical trials and studies before the approval of dabigatran (Pradaxa) in 2010 by the FDA. DOACs, like warfarin, are associated with a risk of bleeding, requiring clearance of the drug from the bloodstream or administration of reversal agents. It is important for physicians to familiarize themselves with the various types of DOACs and their dosages, along with their advantages and disadvantages in comparison to other non-DAOC classes of medications before incorporating them into their patient management plans.

A major advancement in the field of medicine has been the introduction and usage of direct oral anticoagulants (DOACs) such as dabigatran (Pradaxa), apixaban (Eliquis), and rivaroxaban (Xarelto). DOACs have been increasing in popularity for mainstay anticoagulation pharmacotherapy and are being preferred by physicians over warfarin due to their rapid onset, fewer drug and food interactions, and lack of frequent blood monitoring. DOACs have been indicated in the management of thromboembolic conditions and have been extensively researched in various medical trials and studies before the approval of dabigatran (Pradaxa) in 2010 by the FDA. DOACs, like warfarin, are associated with a risk of bleeding, requiring clearance of the drug from the bloodstream or administration of reversal agents. It is important for physicians to familiarize themselves with the various types of DOACs and their dosages, along with their advantages and disadvantages in comparison to other non-DAOC classes of medications before incorporating them into their patient management plans. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) are frequently prescribed for the management of atrial fibrillation and venous thrombosis. There is a lack of published data on the utilization of DOACs in individuals who have undergone recent cardiac surgery. The purpose of this study was to evaluate the safety and efficacy of apixaban and rivaroxaban compared to warfarin in patients postcardiac surgery. Methods: In this retrospective cohort study, patients were separated into a DOAC cohort or a warfarin cohort based on the agent they received after cardiac surgery. Patients could be included if they were ≥18 years of age and received or were discharged on either rivaroxaban, apixaban, or warfarin within 7 days after cardiac surgery. The primary outcome for the study was the rate of International Society on Thrombosis and Hemostasis (ISTH) major bleeding during hospitalization and for 30 days following discharge or until first follow‐up appointment. Results: There were a total of 194 patients included in the analysis, 97 in the DOAC cohort and 97 in the warfarin cohort. Four patients (4.1%) in the DOAC group experienced ISTH major bleeding, while 2 patients (2.1%) in the warfarin cohort experienced ISTH major bleeding (p = 0.68). No patients in the DOAC cohort experienced a thrombotic event, whereas 2 patients (2.1%) in the warfarin cohort experienced a thrombotic complication (p = 0.5). Conclusion: Apixaban and rivaroxaban demonstrated similar safety when compared to a matched cohort of warfarin patients. Larger prospective randomized studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Although direct oral anticoagulants (DOACs) for patients with atrial fibrillation (AF) are considered to be safe, over or under anticoagulation and increased bleeding or thromboembolic risk are still considered individually. We aimed to investigate whether there is an association between prothrombin time and international normalized ratio (PT-INR) or activated partial thromboplastin time (aPTT) ratio, and the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding among AF patients taking rivaroxaban or dabigatran. Methods: This multi-center cohort study in Taiwan included 3192 AF patients taking rivaroxaban and 958 patients taking dabigatran for stroke prevention where data about PT-INR and aPTT were available. Results: For patients treated with rivaroxaban, a higher INR level was not associated with a higher risk of major bleeding compared to an INR level < 1.1. The risk of IS/SE was lower for patients having an INR ≥ 1.5 compared to those with an INR < 1.1 (aHR:0.57; [95%CI: 0.37–0.87]; p = 0.01). On-label dosing of rivaroxaban and use of digoxin were independent factors associated with an INR ≥ 1.5 after taking rivaroxaban. For patients taking dabigatran, a higher aPTT ratio was not associated with a higher risk of major bleeding. The risk of IS/SE was lower for patients having an aPTT ratio of 1.1–1.2 and 1.3–1.4 than those with an aPTT ratio < 1.1. Conclusions: In AF patients, rivaroxaban with an INR ≥ 1.5 was associated with a lower risk of IS/SE. PT-INR or aPTT ratios were not associated with bleeding events for rivaroxaban or dabigatran. INR may help predict the outcome of AF patients who take rivaroxaban. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) and atrial fibrillation (AF) is a major burden on the health care system. The average occurrence of venous thromboembolism annually is around 108 per 100,000 person-year. DOACs have transformed treatment of coagulation disorder, and now, it is the leading treatment for stroke prevention in AF and VTE prophylaxis and treatment. For more many years, oral vitamin K antagonists (VKAs) were the drug of choice in managing VTE. VKAs treatment is safe and effective if therapeutic international normalized ratio (INR) maintained on the target. However, achieving a stable, therapeutic international normalized ratio (INR) can be difficult and challenging in the context of drug and food interactions and liver disorder, resulting in undertreatment which increases the risk of thromboembolism or overtreatment which might cause bleeding. Herein, we provide an overview of DOACs indications, use in specific comorbidities, monitoring parameters, perioperative management, and reversal agents.

Background: In atrial fibrillation (AF) patients on vitamin K antagonists, a progressive deterioration of renal function is common but there is limited evidence with long‐term use of rivaroxaban. Herein, we investigated the change in renal function in AF patients after 2 years of rivaroxaban treatment. Methods: The EMIR registry is an observational and multicentre study including AF patients treated with rivaroxaban for at least 6 months prior to inclusion. Changes in analytical parameters were recorded during 2 years of follow‐up. Renal function was estimated using the Cockroft‐Gault equation. Results: 1433 patients (638, 44.5% women, mean age of 74.2 ± 9.7 years) were included. Creatinine clearance (CrCl) was available at baseline and at 2 years in 1085 patients. At inclusion, 33.2% of patients had impaired renal function (CrCl <60 ml/min). At 2 years, we were not able to find changes in the proportion of patients with impaired renal function, which increased to 34.6% (p = 0.290). However, the baseline mean CrCl was 76.0 ± 30.5 ml/min and slightly improved at 2 years (77.0 ± 31.8 ml/min; p = 0.014). Overall, the proportion of patients with CrCl <60 ml/min at baseline that had CrCl ≥60 ml/min at 2 years was significantly higher compared to that of patients with CrCl ≥60 ml/min at baseline and CrCl <60 ml/min after (22.2% vs. 13.1%; p < 0.001) Conclusions: In AF patients on long‐term rivaroxaban therapy, a decrease in renal function was not observed. We even observed a slight improvement in the patients with renal impairment. These results reinforce the idea that rivaroxaban may be a safe option even in patients with renal impairment. [ABSTRACT FROM AUTHOR]

Background: The use of rivaroxaban in clinical practice often deviates from manufacturer prescribing information. No studies have demonstrated an association between this practice and improved outcomes. Methods: We used the RIETE registry to assess the clinical characteristics of patients with pulmonary embolism (PE) who received off-label rivaroxaban, and to compare their 3-month outcomes with those receiving the labeled therapy. The patients were classified into four subgroups: (1) labeled therapy; (2) delayed start; (3) low doses and (4) both conditions. Results: From May 2013 to May 2022, 2490 patients with PE received rivaroxaban: labeled therapy—1485 (58.6%); delayed start—808 (32.5%); low doses—143 (5.7%); both conditions—54 (2.2%). Patients with a delayed start were more likely to present with syncope, hypotension, raised troponin levels and more severe abnormalities on the echocardiogram than those on labeled therapy. Patients receiving low doses were most likely to have cancer, recent bleeding, anemia, thrombocytopenia or renal insufficiency. During the first 3 months, 3 patients developed PE recurrence, 4 had deep-vein thrombosis, 11 had major bleeding and 16 died. The rates of major bleeding (11 vs. 0; p < 0.001) or death (15 vs. 1; OR: 22.5; 95% CI: 2.97–170.5) were higher in patients receiving off-label rivaroxaban than in those on labeled therapy, with no differences in VTE recurrence (OR: 1.11; 95% CI: 0.25–6.57). Conclusions: In patients with severe PE, the start of rivaroxaban administration was often delayed. In those at increased risk for bleeding, it was often prescribed at low doses. Both subgroups had a worse outcome than those on labeled rivaroxaban. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) and atrial fibrillation (AF) is a major burden on the health care system. The average occurrence of venous thromboembolism annually is around 108 per 100,000 person-year. DOACs have transformed treatment of coagulation disorder, and now, it is the leading treatment for stroke prevention in AF and VTE prophylaxis and treatment. For more many years, oral vitamin K antagonists (VKAs) were the drug of choice in managing VTE. VKAs treatment is safe and effective if therapeutic international normalized ratio (INR) maintained on the target. However, achieving a stable, therapeutic international normalized ratio (INR) can be difficult and challenging in the context of drug and food interactions and liver disorder, resulting in undertreatment which increases the risk of thromboembolism or overtreatment which might cause bleeding. Herein, we provide an overview of DOACs indications, use in specific comorbidities, monitoring parameters, perioperative management, and reversal agents. [ABSTRACT FROM AUTHOR]

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Background: In the treatment of atrial fibrillation (AF), anticoagulant medications such as warfarin and rivaroxaban are commonly prescribed to reduce the risk of ischaemic strokes, and other thromboembolic events. Research has highlighted advantages and disadvantages of each of these medications, but there remains an absence of qualitative evidence regarding the lived experiences of AF patients. The present study helps address this gap and obtain a greater understanding of the patient experience and beliefs surrounding their anticoagulant medication. Method: Semi‐structured qualitative interviews with a purposive sample of 20 participants (10 warfarin, 10 rivaroxaban). Interviews were transcribed verbatim and thematically analysed. Results: Data analysis led to the generation of three key themes: positive perceptions of medication, distrust of alternatives, and inconsistencies in support experiences. Conclusions: Positive perceptions of one anticoagulant medication (ACM) and distrust of alternatives may influence patients' confidence in switching medications. This is potentially problematic where there is a lack of patient engagement in medication changes, as seen during the COVID pandemic. Gaps in patient understanding of anticoagulation, including lack of clarity around medications selection and misconceptions about treatment, were evident. By addressing these misconceptions, clinicians may be better positioned to support people with AF in self‐management of their ACM. [ABSTRACT FROM AUTHOR]

Apixaban and rivaroxaban are the two most prescribed direct factor Xa inhibitors. With the increased use of DOACs in real-world settings, safety and efficacy concerns have emerged, particularly regarding their concomitant use with other drugs. Increasing evidence highlights drug–drug interactions with CYP3A/P-gp modulators leading to adverse events. However, current recommendations for dose adjustment do not consider CYP3A/P-gp genotype and phenotype. We aimed to determine their impact on apixaban and rivaroxaban blood exposure. Three-hundred hospitalized patients were included. CYP3A and P-gp phenotypic activities were assessed by the metabolic ratio of midazolam and AUC0–6h of fexofenadine, respectively. Relevant CYP3A and ABCB1 genetic polymorphisms were also tested. Capillary blood samples collected at four time-points after apixaban or rivaroxaban administration allowed the calculation of pharmacokinetic parameters. According to the developed multivariable linear regression models, P-gp activity (p < 0.001) and creatinine clearance (CrCl) (p = 0.01) significantly affected apixaban AUC0–6h. P-gp activity (p < 0.001) also significantly impacted rivaroxaban AUC0–6h. The phenotypic switch (from normal to poor metabolizer) of P-gp led to an increase of apixaban and rivaroxaban AUC0–6h by 16% and 25%, respectively, equivalent to a decrease of 38 mL/min in CrCl according to the apixaban model. CYP3A phenotype and tested SNPs of CYP3A/P-gp had no significant impact. In conclusion, P-gp phenotypic activity, rather than known CYP3A/P-gp polymorphisms, could be relevant for dose adjustment. [ABSTRACT FROM AUTHOR]

Introduction: Anticoagulants are among the most frequently prescribed medications in the United States. Racial and ethnic disparities in incidence and outcomes of thrombotic disorders are well-documented, but differences in response to anticoagulation are incompletely understood. Objective: The objective of this review is to describe the impact of race and ethnicity on surrogate and clinical end points related to anticoagulation and discuss racial or ethnic considerations for prescribing anticoagulants. Methods: A PubMed and MEDLINE search of clinical trials published between 1950 and May 2018 was conducted using search terms related to anticoagulation, specific anticoagulant drugs, race, and ethnicity. References of identified studies were also reviewed. English-language human studies on safety or efficacy of anticoagulants reporting data for different races or ethnicities were eligible for inclusion. Results: Seventeen relevant studies were identified. The majority of major trials reviewed for inclusion either did not include representative populations or did not report on the racial breakdown of participants. Racial differences in pharmacokinetics, dosing requirements, drug response, and/or safety end points were identified for unfractionated heparin, enoxaparin, argatroban, warfarin, rivaroxaban, and edoxaban. Conclusions: Race appears to influence drug concentrations, dosing, or safety for some but not all direct oral anticoagulants. This information should be considered when selecting anticoagulant therapy for nonwhite individuals. [ABSTRACT FROM AUTHOR]

Background/Aim: Although direct oral anticoagulants (DOACs) are as safe and effective as conventional anticoagulants for treating venous thromboembolism (VTE), we have insufficient evidence justifying their use in patients with active cancer. We investigated the safety and effectiveness of DOACs in patients with active cancer. Patients and Methods: To investigate the safety and efficacy of DOACs, we retrospectively extracted 312 consecutive patients with active cancer who were prescribed edoxaban, rivaroxaban or apixaban for VTE. Results: The most common primary cancer sites were the lung, stomach, colon/rectum, hematology, ovary, and pancreas. Fifty patients (16%) discontinued DOACs due to clinically relevant bleeding; major bleeding events occurred in 18 patients (5.4%). Thrombosis reduced or resolved in 144 of 167 evaluable patients (86%). In particular, pulmonary embolism was reduced or resolved in 46 of 50 patients (92%). Conclusion: Our findings revealed that DOACs for cancerassociated VTE are as safe and effective as conventional anticoagulation therapy. [ABSTRACT FROM AUTHOR]

The classical oral anticoagulants are increasingly being replaced in clinical practice by new antithrombotic drugs, which act by enabling direct inhibition of coagulation factor IIa (FIIa) or factor Xa (FXa). These drugs have multiple acronyms, including NOACs (new, non-vitamin K antagonist) or DOACs (direct oral anticoagulants), and currently include dabigatran (FIIa inhibitor), and rivaroxaban, apixaban, and edoxaban (FXa inhibitors). These drugs are approved for stroke prevention in patients with non-valvular atrial fibrillation and the prevention and treatment of venous thromboembolism. The "mantra" that DOACs do not require laboratory monitoring is not entirely correct because laboratory testing for drug effects is needed in many situations, because they influence hemostasis tests and in situations in which urgent measurement of DOACs is required. This should be very important to consider in the clinical situation for numbers of indications and increasing numbers of patients on DOACs therapy. The main aim of this article is to provide practical issues to general laboratory testing for DOACs, as well as to help avoid diagnostic errors associated with hemostasis testing. The assays for DOAC quantification must be available in medical centers on a whole day basis, to facilitate optimal drug management in conditions when things go wrong or in urgent cases of immediate reversal of anticoagulation or appropriate administration of a specific antidote.

Given the growing use of direct oral anticoagulants, particularly in the elderly population, it is important as an emergency physician to be well versed on the methods of emergent reversal of these agents in the bleeding patient. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants are being increasingly used in patients with non-valvular atrial fibrillation and venous thromboembolism, due to their improved efficacy/ safety ratio, a predictable anticoagulant effect without need for routine coagulation monitoring, and fewer food and drug interactions compared with vitamin K antagonists. Gastrointestinal bleeding remains a serious complication, whose management is challenging for gastroenterologists due to the lack of a standardized clinical approach. Clinical experience on periendoscopic management of these drugs is still limited and there is a paucity of clinical data supporting guidelines recommendations', and this ultimately turns out in different, unsubstantiated and potentially harmful practices of patient management. Present study will provide a thorough revision on the risk of GI bleeding for DOAC therapy and the identification of patient risk factors to individualize treatment. Moreover, the approach to management of DOACs in case of bleeding complications is discussed, and an algorithm of different strategies in presence or not of plasma level measurement is proposed. Finally the periendoscopic management for elective procedures will be reviewed, at the light of the guideline recommendations and new evidences from observational studies. [ABSTRACT FROM AUTHOR]

New guideline recommendations prefer direct oral anticoagulants (DOACs) over warfarin in DOAC-eligible patients with atrial fibrillation and patients with venous thromboembolism. As expected with all antithrombotic agents, there is an associated increased risk of bleeding complications in patients receiving DOACs that can be attributed to the DOAC itself, or other issues such as acute trauma, invasive procedures, or underlying comorbidities. For the majority of severe bleeding events, the widespread approach is to withdraw the DOAC, then provide supportive measures and "watchful waiting" with the expectation that the bleeding event will resolve with time. However, urgent reversal of anticoagulation may be advantageous in patients with serious or life-threatening bleeding or in those requiring urgent surgery or procedures. Until recently, the lack of specific reversal agents, has affected the uptake of these agents in clinical practice despite a safer profile compared to warfarin in clinical trials. In cases of life-threatening or uncontrolled bleeding or when patients require emergency surgery or urgent procedures, idarucizumab has been recently approved for reversal of anticoagulation in dabigatran-treated patients and andexanet alfa for factor Xa inhibitor-treated treated patients. The current review summarizes the current clinical evidence and scope of these agents with the potential impact on DOAC use in clinical practice. [ABSTRACT FROM AUTHOR]

Clotting test results are currently not useful for estimating direct oral anti-coagulant (DOAC) concentrations because baseline results vary. DOAC Stop is a DOAC extracting agent with no effect on clotting factors. We investigated if aPTT (activated partial thromboplastin time) and dRVVT (dilute Russells viper venom time) results might correlate better with DOAC concentrations if results after DOAC extraction were used to estimate a "before/after" value (Correction Ratio). We used activated partial thromboplastin time (aPTT, PTT-LA) and dilute Russells viper venom time clotting test (dRVVT) results previously recorded on DOAC patient plasmas (25 dabigatran, 15 apixaban, 19 rivaroxaban) without known thrombotic risk factors before and after DOAC extraction. DOAC concentrations had been determined by standard chromogenic assays. Correlations between aPTT and dabigatran, apixaban, and rivaroxaban concentrations were initially poor (0.64, 0.15 and 0.39 respectively). However, they improved significantly to 0.94, 0.89 and 0.80 when the ratios of initial aPTT to the aPTT obtained after DOAC extraction were plotted against DOAC concentration. Still better correlations (0.99, 0.97, 0.95) and much higher sensitivities to the DOACs were obtained when dRVVT (LA Confirm) tests were used following this procedure on the same samples. The correlations of aPTT and dRVVT tests with DOAC concentrations were significantly improved by using the ratio of result "before" to those "after" DOAC extraction. The results indicate that dRVVT (especially LA Confirm) and similar tests might be useful for determining DOAC concentrations more reliably and with better sensitivity than currently possible with clotting tests. • Extraction of DOACs by DOAC Stop allows baseline clotting test results to be estimated • The "Correction Ratio" is the clotting test result before divided by that after DOAC extraction. • The CR correlated much better with DOAC concentration than initial results. • The best test for this was high phospholipid dRVVT reagent. • This procedure permits quick estimation of DOACs from simple clotting tests via appropriate calibration curves. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Direct oral anticoagulants can potentially provide a more convenient oral alternative for the management of left ventricular thrombi than Warfarin. These medications do not require frequent monitoring and have less drug‐drug interactions. Randomized controlled trials are needed to further demonstrate their efficacy and safety in this setting. Direct oral anticoagulants can potentially provide a more convenient oral alternative for the management of left ventricular thrombi than Warfarin. These medications do not require frequent monitoring and have less drug‐drug interactions. Randomized controlled trials are needed to further demonstrate their efficacy and safety in this setting. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) have expanded options for treating patients with atrial fibrillation (AF). However, DOACs are not warfarin substitutes, and NPs need to be aware of the difference. DOACs are first-line agents when treating AF, yet warfarin has not been replaced. Individualized patient characteristics drive current guidelines. [ABSTRACT FROM AUTHOR]

We report a patient with pulmonary embolism and deep vein thrombosis induced by cancer chemotherapy who received successful anticoagulation using a single-drug approach with rivaroxaban. Cancer-associated thrombosis (CAT) is a leading cause of non-cancer death in patients with cancer, which is induced by cancer itself and/or chemotherapy agents including cisplatin and gemcitabine. By contrast, hemorrhagic state is another feature of advanced cancer. In these opposite conditions of cancer patients, CAT have to be controlled by appropriate anticoagulation. This case shows potential for single-drug approach with rivaroxaban and direct oral anticoagulants being effective and safety strategy against CAT. < Learning objective: Single-drug approach of direct oral anticoagulants (DOACs) against CAT induced by cisplatin and gemcitabine showed satisfactory anticoagulation without heparin and warfarin. CAT has been important issue in oncology field, and single-drug approach of DOACs could be an effective and safety strategy for anticoagulation against CAT.> [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) offer noninferior efficacy and improved safety compared to vitamin K antagonists (VKAs) for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Unlike VKAs, DOACs do not require routine laboratory monitoring of anticoagulant effect and dose adjustment. In certain situations, however, laboratory assessment of anticoagulant effect may be desirable. Here we review the utility of currently available assays for assessment of DOAC effect and recommend an optimal assessment strategy for each drug, including calibrated dilute thrombin time or ecarin-based assays for dabigatran and calibrated anti-Xa activity assays for the factor Xa inhibitors. We also discuss reversal strategies, both specific and nonspecific, for each drug, including the preferential use of idarucizumab for the reversal of dabigatran and two agents, andexanet and ciraparantag, currently under development for the reversal of rivaroxaban, apixaban, and edoxaban. [ABSTRACT FROM AUTHOR]

New oral anticoagulants have changed the paradigm of anticoagulation management, improving patient convenience as well as possibly reducing the incidence of spontaneous intracranial haemorrhage. However, concerns remain regarding these agents due to the lack of monitoring capacity and availability of readily accessible specific antidotes. This is particularly pertinent in the older population, specifically the frail elderly, who have multiple comorbidities, higher risk of falls requiring intervention and increased risk of bleeding. This group has not been specifically studied in randomised controlled trials and hence extrapolation of trial data to this population should be done carefully. No national guidelines exist for the safe prescription and monitoring of new oral anticoagulants in frail older people. In this article, we provide a review of the currently available new oral anticoagulants in Australia, with a geriatric haematological perspective, including evidence from clinical trials and subsequent meta-analyses, the concerns regarding these new agents, and how these impact on the older population. [ABSTRACT FROM AUTHOR]