Reversal of direct oral anticoagulants: Guidance from the SSC of the ISTH: R1.

The currently approved direct oral anticoagulants (DOACs) are increasingly used in clinical practice. Although serious bleeding risks are lower with DOACs compared to vitamin K antagonists, bleeding remains the most frequent side effect. Andexanet-alfa and idarucizumab are the currently approved specific reversal agents for oral FXa inhibitors and dabigatran, respectively. Our prior guidance document was published in 2106, but with more information available on the utility and increased use of these reversal agents and other bleeding management strategies, we have updated this ISTH guidance document on DOAC reversal. In this narrative review, we compare the mechanism of action of specific and non-specific reversal agents, review the clinical data supporting their use, and provide guidance on when reversal is indicated. In addition, we briefly discuss the reversal of oral FXIa inhibitors, a new class of DOACs currently under clinical development.

Anticoagulation and Antiplatelet Regimen in Cardiac Transplant. Clinical Characteristics, Outcomes, and Blood Product Transfusion.

BACKGROUND: We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy. METHODS: A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events. RESULTS: Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%). CONCLUSIONS: In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.

Anticoagulation reversal (vitamin K, prothrombin complex concentrates, idarucizumab, andexanet-α, protamine).

Bleeding events are common in patients prescribed anticoagulants and can have devastating consequences. Several specific and nonspecific agents have been developed to reverse the effects of anticoagulant drugs or toxins. Vitamin K, as the oldest of these antidotes, specifically counteracts the effects of pharmaceuticals and rodenticides designed to deplete stores of vitamin K-dependent factors. In cases of life-threatening bleeding, the addition of prothrombin complex concentrates (PCCs) allows for the immediate replacement of coagulation factors. While the use of PCCs has been extended to the non-specific reversal of the effects of newer direct oral anticoagulants, the specific agents idarucizumab, targeting dabigatran and andexanet-α, binding factor Xa inhibitors, have recently been developed and are being preferentially recommended by most guidelines. However, despite having rapid effects on correcting coagulopathy, there is to date a lack of robust evidence establishing the clear superiority of direct oral anticoagulant-specific reversal agents over PCCs in terms of haemostatic efficacy, safety or mortality. For andexanet-α, a potential signal of increased thromboembolic risks, comparatively high costs and low availability might also limit its use, even though emerging evidence appears to bolster its role in intracranial haemorrhage. Protamine is the specific agent for the reversal of unfractionated heparin anticoagulation used mainly in cardiovascular surgery. It is much less effective for low molecular weight heparin fragments and is usually reserved for cases with life-threatening bleeding.

[Overdosing of direct oral anticoagulants]. / Überdosierung von direkten oralen Antikoagulanzien.

BACKGROUND: Direct oral anticoagulants (DOAC) are increasingly used for prophylaxis and treatment of thromboembolic events. Incorrectly dosed DOAC treatment is associated with excess mortality. PURPOSE: This article aims at raising awareness of DOAC overdosing and its causes as well as presenting a diagnostic and therapeutic work-up. MATERIAL AND METHODS: Based on a case presentation, a structured review of the current literature on DOAC overdosing was performed and treatment recommendations were extracted. RESULTS: In addition to wittingly or unwittingly increased DOAC intake, common causes of overdose are inadequate dose adjustment for concomitant medication or comorbidities. Global coagulation testing should be supplemented with DOAC-specific testing. Severe bleeding and the need for invasive diagnostics or urgent surgery represent indications for treating DOAC overdoses. Based on the cause of an DOAC overdose, active charcoal, endoscopic pill rescue, antagonization with idarucizumab or andexanet alfa and the targeted substitution of coagulation factors represent treatment options. CONCLUSION: The sensitization of clinicians is important to ensure a timely diagnosis and adequate treatment of DOAC overdosing. This report provides an overview of current knowledge on diagnostics and treatment; however, further studies are necessary to improve the existing algorithms.

Idarucizumab in dabigatran-treated patients with acute stroke: a review and clinical update.

Idarucizumab is an antibody fragment specific for the immediate reversal of dabigatran anticoagulation effects. The use of idarucizumab is approved for dabigatran-treated patients suffering from life-threatening or uncontrolled bleeding and those in need of urgent surgery or invasive procedures. Data from randomized controlled clinical trials and real-world experience provide reassuring evidence about the efficacy and safety of idarucizmab use in patients with acute stroke. In this narrative review, we summarize the available real-world evidence and discuss the relevance and importance of idarucizumab treatment in acute stroke patients in everyday clinical practice. In addition, we also discuss special issues like prothrombin complex concentrate application as an alternative to idarucizumab, its application before endovascular therapy, sensitivity of thrombi to lysis, and necessary laboratory examinations.

ANMCO/SIMEU consensus document on the use of reversal agents for antithrombotic therapies in patients with ongoing bleeding or at high risk of haemorrhagic events.

In recent decades, an incredible evolution in antithrombotic therapies used for treating patients with atherosclerosis, atrial fibrillation, and venous thromboembolism has been observed, leading to the availability of increasingly safe drugs. Nonetheless, bleeding complications remain a significant concern, with considerable health, social, and economic implications. To improve the acute management of patients experiencing or at risk for major bleeding events, specific reversal agents for antithrombotic drugs have been recently developed. While these agents demonstrate effectiveness in small-scale pharmacodynamic studies and clinical trials, it is imperative to balance the benefits of reversing antiplatelet or anticoagulant therapy against the risk of prothrombotic effects. These risks include the potential loss of antithrombotic protection and the prothrombotic tendencies associated with bleeding, major surgery, or trauma. This joint document of the Italian Association of Hospital Cardiologists (Associazione Nazionale Medici Cardiologi Ospedalieri) and the Italian Society of Emergency Medicine (Società Italiana di Medicina d'Emergenza-Urgenza) delineates the key features and efficacy of available reversal agents. It also provides practical flowcharts to guide their use in patients with active bleeding or those at elevated risk of major bleeding events.

Is there a role for the laboratory monitoring in the management of specific antidotes of direct oral anticoagulants?

Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote. Other antidotes or hemostatic agents are still under preclinical or clinical development, the most advanced being ciraparantag. DOAC plasma levels measurement allows to appropriately select patient for antidote administration and may prevent unnecessary prescription of expensive molecules in some acute clinical settings. However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes.

Latest advances in the reversal strategies for direct oral anticoagulants.

BACKGROUND: Since the late 2000s, Europe has granted approval for various thrombotic risk-related uses of direct oral anticoagulants (DOACs). Unlike traditional anticoagulants, DOACs do not necessitate routine coagulation monitoring. Nevertheless, clinical practice often encounters bleeding events associated with these medications, making the need for effective reversal strategies evident. OBJECTIVES: The study aims to take stock of current reversal strategies for DOACs, with a particular emphasis on the latest compounds that have been developed or are currently under development. METHODS: For obtaining information regarding the ongoing reversal strategies and the compounds under development, we referred to ClinicalTrials website, PubMed, and Google Scholar. RESULTS: In 2024, two specific antidotes to DOACs have already received approval when reversal of anticoagulation is needed owing to life-threatening or uncontrolled bleeding: idarucizumab that reverses the effects of dabigatran, and andexanet alfa, designed to counteract activated factor X inhibitors such as apixaban and rivaroxaban. Furthermore, ciraparantag, a potential universal reversal agent, is currently in advanced stages of clinical development. Concerns remain regarding the safety of specific reversal agents, especially concerning the risk of thrombosis. Additionally, the cost of these antidotes remains high. Consequently, nonspecific strategies to counteract anticoagulant medications, including activated charcoal, hemodialysis, and concentrates of coagulation factors, still have utility. CONCLUSION: With the validation of specific and nonspecific antidotes, DOACs could supplant traditional oral anticoagulants. This progress represents a significant advancement in anticoagulation therapy. However, ongoing research is crucial to address remaining safety concerns of the specific reversion agents of DOACs in clinical practice.

Cardiac Tamponade and Duodenal Hemorrhage Caused by Inappropriate Use of Dabigatran in a Patient With End-Stage Renal Failure: A Case Report.

A 72-year-old man with end-stage renal failure, receiving 220 mg of dabigatran for chronic atrial fibrillation, was admitted with generalized edema and shortness of breath. Cardiac tamponade caused by pericardial hemorrhage due to inappropriate dabigatran use was treated with pericardial drainage and idarucizumab. Although coagulability normalized, consecutive duodenal hemorrhages occurred, requiring arterial embolization for hemostasis. In cases of severely impaired renal function, the usual dose of idarucizumab may not be sufficient to reverse the effects of dabigatran. Therefore, we considered the need for repeated idarucizumab administration to prevent recurrent bleeding.

Dabigatran pharmacokinetic-pharmacodynamic in sheep: Informing dose for anticoagulation during cardiopulmonary bypass.

BACKGROUND: The effect of the anticoagulant, dabigatran, and its antagonist, idarucizumab, on coagulation remains poorly quantified. There are few pharmacokinetic-pharmacodynamic data available to determine dabigatran dose in humans or animals undergoing cardiopulmonary bypass. METHODS: Five sheep were given intravenous dabigatran 4 mg/kg. Blood samples were collected for thromboelastometric reaction time (R-time) and drug assay at 5, 15, 30, 60, 120, 240, 480 min, and 24 h. Plasma dabigatran concentrations and R-times were analyzed using an integrated pharmacokinetic-pharmacodynamic model using non-linear mixed effects. The impact of idarucizumab 15 mg/kg administered 120 min after dabigatran 4 mg/kg and its effect on R-time was observed. RESULTS: A 2-compartment model described dabigatran pharmacokinetics with a clearance (CL 0.0453 L/min/70 kg), intercompartment clearance (Q 0.268 L/min/70 kg), central volume of distribution (V1 2.94 L/70 kg), peripheral volume of distribution (V2 9.51 L/70 kg). The effect compartment model estimates for a sigmoid EMAX model using Reaction time had an effect site concentration (Ce50 64.2 mg/L) eliciting half of the maximal effect (EMAX 180 min). The plasma-effect compartment equilibration half time (T1/2keo) was 1.04 min. Idarucizumab 15 mg/kg reduced R-time by approximately 5 min. CONCLUSIONS: Dabigatran reversibly binds to the active site on the thrombin molecule, preventing activation of coagulation factors. The pharmacologic target concentration strategy uses pharmacokinetic-pharmacodynamic information to inform dose. A loading dose of dabigatran 0.25 mg/kg followed by a maintenance infusion of dabigatran 0.0175 mg/kg/min for 30 min and a subsequent infusion dabigatran 0.0075 mg/kg/min achieves a steady state target concentration of 5 mg/L in a sheep model.

2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

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.

2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of 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.

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients With Recent Direct Oral Anticoagulant Use: A Systematic Review and Meta-Analysis.

BACKGROUND: Intravenous thrombolysis (IVT) is an effective stroke therapy that remains underused. Currently, the use of IVT in patients with recent direct oral anticoagulant (DOAC) intake is not recommended. In this study we aim to investigate the safety and efficacy of IVT in patients with acute ischemic stroke and recent DOAC use. METHODS AND RESULTS: A systematic review and meta-analysis of proportions evaluating IVT with recent DOAC use was conducted. Outcomes included symptomatic intracranial hemorrhage, any intracranial hemorrhage, serious systemic bleeding, and 90-day functional independence (modified Rankin scale score 0-2). Additionally, rates were compared between patients receiving IVT using DOAC and non-DOAC by a random effect meta-analysis to calculate pooled odds ratios (OR) for each outcome. Finally, sensitivity analysis for idarucizumab, National Institutes of Health Stroke Scale, and timing of DOAC administration was completed. Fourteen studies with 247 079 patients were included (3610 in DOAC and 243 469 in non-DOAC). The rates of IVT complications in the DOAC group were 3% (95% CI, 3-4) symptomatic intracranial hemorrhage, 12% (95% CI, 7-19) any ICH, and 0.7% (95%CI, 0-1) serious systemic bleeding, and 90-day functional independence was achieved in 57% (95% CI, 43-70). The rates of symptomatic intracranial hemorrhage (3.4 versus 3.5%; OR, 0.95 [95% CI, 0.67-1.36]), any intracranial hemorrhage (17.7 versus 17.3%; OR, 1.23 [95% CI, 0.61-2.48]), serious systemic bleeding (0.7 versus 0.6%; OR, 1.27 [95% CI, 0.79-2.02]), and 90-day modified Rankin scale score 0-2 (46.4 versus 56.8%; OR, 1.21 [95% CI, 0.400-3.67]) did not differ between DOAC and non-DOAC groups. There was no difference in symptomatic intracranial hemorrhage rate based on idarucizumab administration. CONCLUSIONS: Patients with acute ischemic stroke treated with IVT in recent DOAC versus non-DOAC use have similar rates of hemorrhagic complications and functional independence. Further prospective randomized trials are warranted.

Retrospective Observational Study of Patients With Subdural Hematoma Treated With Idarucizumab.

Use of anticoagulants is increasing with the aging of societies. The safe first-line drug is likely to be a direct oral anticoagulant (DOAC), but outcomes of treatment of traumatic brain injury (TBI) with anticoagulants are uncertain. Therefore, we examined the clinical effect of idarucizumab as reversal therapy in elderly patients with TBI who were treated with dabigatran. A retrospective multi-center observational study was performed in patients ≥65 years of age who developed acute traumatic subdural hematoma during treatment with dabigatran and underwent reversal therapy with idarucizumab. The items examined included patient background, neurological and imaging findings at arrival, course after admission, complications, and outcomes. A total of 23 patients were enrolled in the study. The patients had a mean age of 78.9 years. Cause of TBI was fall in 60.9% of the subjects. Mean Glasgow Coma Scale score at arrival was 8.7; anisocoria was present in 31.8% of cases. Exacerbation of consciousness was found in 30.4%, but only in 13.3% of subjects treated with idarucizumab before consciousness and imaging findings worsened. Dabigatran was discontinued in 81.8% of cases after hematoma development, with a mean withdrawal period of 12.1 days. The favorable outcome rate was 21.7%, and mortality was 39.1%. In multi-variate analysis, timing of idarucizumab administration was associated with a favorable outcome. There were ischemic complications in 3 cases (13.1%), and all three events occurred ≥7 days after administration of idarucizumab. These findings suggest that in cases that develop hematoma during treatment with dabigatran, it is important to administer idarucizumab early and restart dabigatran after conditions stabilize.

Reversing dabigatran effect with idarucizumab to enable intravenous thrombolysis in patients with acute ischaemic stroke - a single centre experience.

INTRODUCTION: Our study analysed the safety and effectiveness of idarucizumab in enabling intravenous thrombolysis (IVT) in dabigatran-treated patients with acute ischaemic stroke (AIS). CLINICAL RATIONALE FOR THE STUDY: New oral anticoagulants (NOAC), including dabigatran, are the first-choice treatment option for preventing ischaemic stroke in patients with non-valvular atrial fibrillation (AF). However, a significant percentage of AF patients develops AIS despite NOAC treatment. According to current guidelines, treatment with IVT is contraindicated in patients who have received NOAC within the last 48 hours. Idarucizumab is a fragment of a monoclonal antibody that reverses the anticoagulation effect of dabigatran. The latest research shows that it can enable safe and successful IVT in patients with recent dabigatran intake, but more data is needed to confirm the safety and effectiveness of such treatment. MATERIAL AND METHODS: Our study included dabigatran-treated patients who received idarucizumab to allow AIS treatment with IVT in the University Hospital in Kraków (Poland) from December 2018 to June 2023. We gathered data on their past medical history, stroke severity, course of treatment and outcomes as defined by modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) scores at discharge. A good functional outcome was defined as mRS 0-2 points at discharge. RESULTS: This observational study included 19 patients (13 male and six female) with a median age of 74 (IQR = 13) years. In all patients (100%), the reason for dabigatran treatment was AF. A good functional outcome after treatment (mRS 0-2) was achieved in 68.4% of patients, but mRS was already ≥ 3 points before stroke onset in three (15.8%) patients. Haemorrhagic transformation of stroke occurred in three (15.8%) patients, including symptomatic intracranial haemorrhage in two (10.5%). The mortality rate was 5.3%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study results are in line with previous research on this topic, showing that IVT after idarucizumab can be successfully administered and is reasonably safe in dabigatran-treated patients with AIS.

Evidence-based Management of Major Bleeding in Patients Receiving Direct Oral Anticoagulants: An Updated Narrative Review on the Role of Specific Reversal Agents.

The indications of direct oral anticoagulants (DOACs) have expanded over the past 15 years. DOACs are effective and safe oral anticoagulants associated with lower bleeding risks and mortality than vitamin K antagonists. However, DOAC users are prone to a considerable bleeding risk, which can occur at critical sites or lead to severe life-threatening conditions. Recent statistics indicated that major bleeding occurs in up to 6.62 DOAC users per 100 treatment years. With the increased use of DOACs in clinical practice, DOAC-associated major bleeding is expected to be encountered more frequently in the emergency department. The current international guidelines recommend specific reversal agents for the management of DOAC users with severe bleeding to reverse the anticoagulant effect and restore normal hemostasis. An individualized assessment was incorporated in specific clinical situations to guide the decision pathway of major bleeding management. However, specific reversal agents are unavailable or have limited availability in many countries, which is expected to negatively impact the clinical outcomes of DOAC-associated major bleeding. Limited real-world evidence is available from these countries regarding the clinical outcomes of patients with DOAC-associated major bleeding. This narrative review provided an updated assessment of the evidence-based approaches for the management of major bleeding in DOAC users. We also explored the clinical outcomes of patients with major bleeding from clinical settings where specific reversal agents are unavailable.

Idarucizumab for Emergency Reversal of the Anticoagulant Effects of Dabigatran: Final Results of a Japanese Postmarketing Surveillance Study.

INTRODUCTION: Idarucizumab, a monoclonal antibody fragment that rapidly reverses the anticoagulant effects of dabigatran, was approved in Japan in September 2016, at which time an all-case, postmarketing surveillance (PMS) study was initiated to collect data on idarucizumab in Japanese patients. Interim results were published previously, and the final results are reported herein. METHODS: This multicenter, open-label, uncontrolled, non-interventional PMS study was conducted in Japanese patients who received idarucizumab at the approved dose (2 × 2.5 g/50 ml) and had uncontrolled bleeding (group A) or required an emergency procedure (group B). The primary endpoint was the frequency of adverse drug reactions (ADRs). The secondary endpoint was the maximum extent of reversal of the anticoagulant effects of dabigatran, within 4 h of idarucizumab administration, based on activated partial thromboplastin time (aPTT). RESULTS: The final analysis included 804 patients. ADRs during the idarucizumab treatment and post-treatment periods were reported in 17 of 542 patients (3.1%) in group A and 12 of 240 patients (5.0%) in group B. Thrombotic events were reported in 22 patients (4.1%) in group A and 15 patients (6.3%) in group B, and hypersensitivity occurred in four (0.7%) and five patients (2.1%), respectively. Among 793 patients evaluated for effectiveness, 78 in group A and 26 in group B had aPTT data at baseline (immediately before idarucizumab administration) and within 4 h of idarucizumab administration; in these patients, median maximum percentage reversal within 4 h of idarucizumab administration was 100%. CONCLUSIONS: The final analysis from the PMS study confirms previous findings suggesting that idarucizumab can safely and effectively reverse the anticoagulant effects of dabigatran in Japanese patients in clinical practice. The results support the continued use of idarucizumab in Japan. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov (NCT02946931).

Atrial fibrillation is an irregular heart rhythm (arrhythmia), and the type of atrial fibrillation not caused by a heart valve problem is known as "non-valvular atrial fibrillation" or NVAF. People with NVAF have an increased risk of ischemic stroke, in which a blood clot (thrombus) blocks an artery in the brain. Drugs that inhibit blood clots, known as anticoagulants, are prescribed to people with NVAF to prevent ischemic stroke. Historically, warfarin has been one of the most prescribed anticoagulant drugs. However, a novel anticoagulant drug, known as dabigatran, has clinical advantages over warfarin and is approved in many countries for people with NVAF. People who take anticoagulants may experience life-threatening bleeding or need urgent surgery, and thus rapid and effective reversal of the anticoagulant effects is critical. The drug idarucizumab specifically binds to dabigatran to reverse its anticoagulant effects in people with uncontrolled bleeding or who require an urgent procedure. Idarucizumab was approved for use in Japan in September 2016. In Japan, drug companies are obligated to collect data after a new drug is launched as an approval condition, which is done through a postmarketing surveillance study. Here, we report the final results of a postmarketing surveillance study conducted between September 2016 and November 2020 to evaluate the safety and effectiveness of idarucizumab in Japanese patients receiving dabigatran. The results of our study show that idarucizumab can safely and effectively reverse the anticoagulant effects of dabigatran in Japanese patients, and support the continued use of idarucizumab in Japan in clinical practice.

Perioperative Myocardial Infarction Following Dabigatran Reversal With Idarucizumab in a Patient Undergoing Orthotopic Liver Transplantation.

Insufficient information is available regarding the administration of anticoagulants, specifically direct oral anticoagulants, in individuals with cirrhosis awaiting liver transplantation. In this report, we present a case of a 66-year-old male with atrial fibrillation treated with dabigatran who received idarucizumab prior to orthotopic liver transplantation. Hemostatic status was monitored throughout the procedure with both conventional hemostatic tests and point-of-care viscoelastic hemostatic assays. The patient suffered an intraoperative myocardial infarction, which could be related to the use of idarucizumab.