Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany—Updated series of 120 cases

Abstract

Background Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth. Aims To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage. Methods Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used. Results One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in n = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0–3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay. Conclusion Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.

Real-world experience with reversal of dabigatran by idarucizumab

“…As these cases are complicated, further research on this subgroup is warranted. Case reports on use of idarucizumab prior to thrombolysis in acute stroke patients have recently been published [26,27]. A Slovenian study similar to ours found two patients (of 17 total) treated for this indication who experienced an improvement in National Institute of Health Stroke Scale and no adverse reactions [28].…”

European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke

“…[172][173][174] For example, idarucizumab has been used to reverse dabigatran activity before alteplase treatment, and this treatment algorithm has been tested in small studies in the prehospital and hospital settings. [176][177][178] However, there are theoretical concerns that idarucizumab may potentiate the prothrombotic activity in the acute phase of ischaemic stroke, and increase the risk of ischaemic events. 172 Nevertheless, such complications were not documented in two national cohorts from Germany and New Zealand reporting the experience of IVT for acute ischaemic stroke patients pretreated with idarucizumab for dabigatran reversal.…”

Intravenous Thrombolysis after Reversal of Dabigatran with Idarucizumab in Acute Ischemic Stroke: A Case Report

“…In a Franch retrospective research, patients with acute ischemic stroke who were treated with dabigatran within 48 hours were recommended for intravenous thrombolysis after idarucizumab's reversal without direct prothrombin activity monitoring [9] .Giannandrea [10] reviewed 55 thrombolytic cases after idarucizumab reversal of dabigatran showed that 81.9% (45 cases) of patients had improved NIHSS score (median 5 points). In a retrospective study of 120 patients with acute ischemic/hemorrhagic stroke in Germany, the e cacy and safety of idarucizumab reversal of dabigatran in intravenous thrombolysis with acute ischemic stroke had been con rmed.However, in patients with hemorrhagic stroke, the application of can prevent the expansion of hematoma and improve the prognosis of patients [11] .…”