Safety Of Idarucizumab Research Articles

Practical use of idarucizumab

The number of patients with indications for direct oral anticoagulants (DOACs) to prevent thrombotic events is steadily growing. However, in 1,1-2,2% of cases, ischemic strokes occur within DOAC therapy. In this case, DOAC use is a limitation for systemic thrombolysis, except for available reversal of anticoagulation. In order to immediately inactivate the anticoagulant effect of dabigatran etexilate (DE), reversal agent idarucizumab is used.Aim. To evaluate the effectiveness and safety of idarucizumab in clinical practice.Material and methods. The study included 9 patients taking DE who developed urgent conditions that required emergency reversal of anticoagulation with idarucizumab.Results. Normalization of thrombin time (TT) was achieved in 7 (77,8%) patients immediately after idarucizumab administration. In two patients, 10 minutes after the administration of a specific DE reversal agent, TT decreased, but did not reach reference values (case 1: TT decreased from 181 to 23,3 seconds; case 2: TT decreased from 181 to 18,3 seconds); 30 minutes after the idarucizumab administration, TT normalization was achieved.Conclusion. Nobody developed clinically significant arterial and/or venous thrombotic events during the entire period of hospitalization. Rapid reversal of anticoagulation with idarucizumab allows immediate systemic thrombolytic therapy or surgery in patients taking DE without the increase of bleeding or thrombosis risk and the need for control coagulation analysis.

Clinical experience with idarucizumab in patients with atrial fi brillation taking dabigatran etexilate

Dabigatran etexilate (DE) is a direct thrombin inhibitor that has been shown to be eff ective and safe in preventing thrombotic events in a number of studies. Currently idarucizumab, which is a monoclonal antibody and a DE antagonist, is used to immediately inactivate the DE-induced eff ect.Objective. Еvaluation of the effi ciency and safety of idarucizumab in patients receiving DE.Material and methods. 6 patients (2 men, 4 women) aged 61 to 86 years (mean age 72.8 ± 10.6 years) receiving DE, who are expected to use idarucizumab in achieving the goal of sTLT or surgery.Results. In none of the patients the use of idarucizumab was accompanied by a decrease in thrombin time of less than 11 seconds which could indicate a hypercoagulable phenomenon. Before inactivation of dabigatran etexilate thrombin time was signifi cantly higher (p < 0.05) than after the administration of the drug. There were no statistically signifi cant diff erences in the concentration of D-dimer before and after the administration of idarucizumab which indicates the absence of procoagulant properties of this drug. None of the patients developed clinically signifi cant arterial and/ or venous thrombotic events such as recurrent IS, myocardial infarction, deep vein thrombosis of the lower extremities and pulmonary embolism, during the entire period of hospitalization.Conclusion. The use of idarucizumab is allowed for systemic thrombolytic therapy and emergency surgical treatment in patients taking DE. Idarucizumab quickly and safely neutralizes the anticoagulant eff ect of DE and doesn’t have a prothrombotic activity.

Use of idarucizumab for emergency surgery in patients taking dabigatran

This article presents modern possibilities for the provision of emergency surgical care to patients with atrial fibrillation, who administered dabigatran etexilate. We describe two clinical situations, in which idarucizumab, a specific dabigatran antagonist, which is a monoclonal antibody fragment that binds dabigatran, was used to neutralize the anticoagulant effect of dabigatran etexilate before emergency surgery. In the first case, the patient developed acute gangrenous calculous cholecystitis, in the second a patient required an urgent epicystostomy. In both cases, the successful outcome of surgical interventions was due to the effective interactions of the team of specialists and adherence to the algorithm for providing emergency care to such patients, as well as the presence of idarucizumab in hospitals. The postoperative management of patients and the timely resumption of anticoagulant therapy to prevent thromboembolic complications is no less important. The presented clinical cases confirm the feasibility of using idarucizumab to provide emergency surgical care to patients on dabigatran etexilate, as well as the need to take into account the possible risk of emergency interventions when anticoagulant therapy is prescribed to patients with atrial fibrillation. This paper discusses special risk groups of patients in whom rapid reversal of anticoagulation is required due to altered hemostasis.We outline data of a prospective cohort study (RE-VERSE AD), which examined the efficacy and safety of idarucizumab in patients with uncontrolled bleeding and in patients requiring urgent surgery. We also present the RE-VECTO study data on the use of idarucizumab in real-life clinical practice.

Effectiveness and safety of idarucizumab in the management of perioperative complications of atrial fibrillation catheter ablation in atrial fibrillation patients under dabigatran therapy

Objective: To investigate the efficacy and safety of idarucizumab in the treatment of perioperative cardiac tamponade and thromboembolic events during catheter ablation in atrial fibrillation (AF) patients under dabigatran therapy. Methods: This study was a retrospective analysis enrolling patients under dabigatran therapy, who underwent catheter ablation for AF at Beijing Anzhen Hospital from January 2019 to December 2020 and developed perioperative cardiac tamponade or acute ischemic stroke (AIS) and received idarucizumab to reverse the anticoagulant effect of dabigatran. Patients' age, sex, renal function, coagulation test and safety events at 30 d after idarucizumab administration were collected and analyzed. The clinical presentation and prognosis were also analyzed. Results: A total of 7 patients were included, 2 (2/7) were male, mean age was (66.3±11.2) years, serum creatinine level was (66.3±13.6) μmol/L, estimated glomerular filtration rate was (89.4±11.2) ml·min-1·1.73 m-2, CHA2DS2-VASc and HAS-BLED scores were (3.2±1.9) and (1.3±1.3), respectively. Five patients (5/7) developed cardiac tamponade during the perioperative period and the time interval to the last dose of dabigatran was (6.3±2.6) h. Idarucizumab was given at (36.4±16.7) min after the definitive diagnosis of cardiac tamponade. A significant decrease of activated partial thromboplastin time was achieved after idarucizumab administration in all five cases. Pericardial puncture and drainage were applied to all patients (5/5) with cardiac tamponade, the drainage volume was (1 037.0±846.9) ml, the retention time of pericardial drainage catheter was (27.9±13.9) h, and the recovery time of anticoagulation was (28.4±13.2) h. One patient (1/5) underwent thoracotomy for hemostasis due to excessive blood loss with the aim of ensuring complete hemostasis. Bleeding occurred in 1 patient (1/5) after the first restart of anticoagulation. AIS occurred in 2 patients (2/7) after operation. One case (1/2) received intravenous thrombolysis after receiving 5.0 g idarucizumab, no hemorrhagic transformation was observed, and the recovery process was satisfactory. Another patient in this group experienced significantly prolonged onset time and 5.0 g idarucizumab was applied before intravascular thrombectomy, there was no bleeding complication in this patient after thrombectomy. At the time of discharge, the consciousness was not significantly improved, and the muscle strength of the right lower limb was recovered somehow compared with that before operation. No hypersensitivity reactions or thrombotic events occurred in these patients within 30 days of the administration of idarucizumab. Conclusion: In AF catheter ablation-associated cardiac tamponade and AIS, idarucizumab is safe and effective in rapidly reversing the anticoagulant effect of dabigatran, use of thrombectomy saves valuable time for timely hemostasis and improvement of cerebral blood circulation.

Efficacy and Safety of Idarucizumab for Rapid Reversal from Dabigatran in Patients Undergoing Orthotopic Heart Transplantation

Purpose To evaluate the effectiveness and safety of idarucizumab before urgent heart transplantation (HTPL) in patients using dabigatran. Methods Between March 2017 and January 2018, consecutive patients who underwent HTPL were evaluated at a single tertiary university hospital. Total 17 HTPL recipients were included in the present study. Patients were grouped into no-anticoagulation therapy (9 patients; Group 1), extracorporeal membrane oxygenator with heparin therapy (3 patients; Group 2), and dabigatran for stroke prevention in atrial fibrillation with idarucizumab reversal before HTPL surgery (5 patients; Group 3). Surgery time (pump time, and total surgery time), amount of packed red blood cell transfusion during surgery, and composite events (bleeding complications, stroke, venous thrombosis, death) during perioperative period were evaluated among three groups. Results Mean age of recipients was (51.2 ± 16.1 years, male 52.9%). Surgery time was longest in group 2 (Total surgery time: 328.3 ± 55.8, 336.4 ± 43.0, 288.8 ± 38.7; pump time 159.0 ± 21.7, 161.9 ± 27.2, 127.0 ± 17.9). Packed RBC transfusion volume was also higher in group 2 (133.3 ± 230.9, 511.1 ± 105.4, 40.0 ± 89.4). When compared with group 2, pump time was significantly shorter (p=0.028) and amount of PC transfusion was significantly lower (p=0.002) in group 3 (figure 1). Amount of transfusion was highest in group 2. Composite events were developed in only group 2 (four patients: vaginal bleeding 1; embolic cerebral infarction 1; venous thrombosis 1; non-cardiac death 1). Conclusion In terms of effectiveness and safety, using idarucizumab before HTPL was beneficial compared with heparin use during ECMO and comparable with non-anticoagulation, non-antiplatelet patients. Candidates for HTPL who are indicated for anticoagulation therapy may consider dabigatran with idarucizumab.

Use of idarucizumab in reversing dabigatran anticoagulant effect: a critical appraisal.

Use of non-vitamin K antagonist oral anticoagulants is spreading in the real world. Despite that, a strong need for antidotes/reversal agents is still reported by several physicians. Idarucizumab is a humanized monoclonal antibody fragment that binds specifically to dabigatran. Idarucizumab was approved in 2015 by the US Food and Drugs Administration and European Medicines Agency for reversal of anticoagulation activity in dabigatrantreated patients. This review briefly summarizes the experimental evidence about effectiveness and safety of idarucizumab. Furthermore, we review the current recommendations and experts’ point of view about the use of antidotes/reversal agents in patients reporting a major bleeding event.