Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany – A national case collection

Kermer, Pawel; Eschenfelder, Christoph; Diener, Hans Christoph; Grond, Martin; Abdalla, Yasser; Althaus, Katharina; Berrouschot, Jörg; Cangür, Hakan; Daffertshofer, Michael; Edelbusch, Sebastian; Gröschel, Klaus; Haase, Claus G.; Harloff, Andreas; Held, Valentin; Kauert, Andreas; Kraft, Peter; Lenz, Arne; Müllges, Wolfgang; Obermann, Mark; Partowi, Someieh; Purrucker, Jan; Ringleb, Peter A.; Röther, Joachim; Rossi, Raluca; Schäfer, Niklas; Schneider, Andréas; Schuppner, Ramona; Seitz, Rüdiger J.; Szabo, Kristina; Wruck, Robert

doi:10.1177/1747493017701944

Cited by 86 publications

(62 citation statements)

References 23 publications

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“…Infarct demarcation before treatment and effective anticoagulation are two impartial IVRTPA contraindications with pathophysiological background, in these cases lack of morphological treatment substrate and treatment‐induced uncontrollable bleeding risk. The latter constellation may lead to an intensified and possibly broadened evaluation of EST eligibility, which seems effective and safe , as well as to antagonizing attempts in the emergency setting followed by IVRTPA treatment . Taking the three major IVRTPA contraindications – time window, demarcation, anticoagulation – into account, an effective TR of over 80% was achieved in our cohort.…”

Section: Discussionmentioning

confidence: 84%

Endovascular stroke treatment does not preclude high thrombolysis rates

Feda¹,

Nikoubashman²,

Schürmann³

et al. 2018

Euro J of Neurology

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Background and purpose In 1995 intravenous recombinant tissue plasminogen activator (IVRTPA) was the first reperfusion therapy to be approved in patients with acute ischaemic stroke (AIS). The significance and impact of IVRTPA in times of modern endovascular stroke treatment (EST) were analysed in a German academic stroke centre. Methods A retrospective observational cohort analysis of 1034 patients with suspected AIS presenting at the emergency department in 2014 was performed. Patients were evaluated for baseline characteristics, reperfusion procedures, IVRTPA eligibility, clinical outcome, symptomatic intracranial haemorrhage (sICH) and mortality. Data acquisition was part of an investigator‐initiated, prospective and blinded end‐point registry. Results In 718 (69%) patients the diagnosis of symptomatic AIS was confirmed. 419 (58%) patients presented within 4.5 h of symptom onset and of those 260 (62%) received reperfusion therapy (IVRTPA alone, n = 183; combination or bridging therapy, n = 60; EST alone, n = 17). Subtracting cases with absolute contraindications for IVRTPA resulted in an effective thrombolysis rate of 82%. sICH occurred in two patients treated with IVRTPA alone (1.1%). The median door‐to‐needle interval was 30 min. Fifty (17%) non‐EST eligible AIS patients presenting within 4.5 h without absolute contraindications did not receive IVRTPA mainly due to mild or regressive symptoms. Most of these untreated IVRTPA eligible patients (82%) were discharged with a good clinical outcome (modified Rankin Scale ≤ 2). Conclusions Intravenous recombinant tissue plasminogen activator remains the most frequently applied reperfusion therapy in AIS patients presenting within 4.5 h of onset in a tertiary stroke centre. An effective thrombolysis rate of over 80% can be achieved without increased rates of sICH.

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Section: Discussionmentioning

confidence: 84%

Endovascular stroke treatment does not preclude high thrombolysis rates

Feda¹,

Nikoubashman²,

Schürmann³

et al. 2018

Euro J of Neurology

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“…[5][6][7] While an INR cut-off value of ≤1.7 is widely accepted for thrombolysis in warfarinised patient based on data from observational studies, there is no such data for DOAC treated patients. [5][6][7] While an INR cut-off value of ≤1.7 is widely accepted for thrombolysis in warfarinised patient based on data from observational studies, there is no such data for DOAC treated patients.…”

Section: Discussionmentioning

confidence: 99%

Ischaemic stroke and transient ischaemic attack on anticoagulants: outcomes in the era of direct oral anticoagulants

Valente

Leung

et al. 2020

Internal Medicine Journal

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Clinical and imaging characteristics of patients receiving direct oral anticoagulants presenting with transient ischaemic attack or stroke are lacking. A retrospective review of all patients who presented to a high-volume primary stroke centre with acute stroke symptoms while prescribed an oral anticoagulant between January 2012 and June 2017. Clinical, radiological characteristics and functional outcomes were examined. Anticoagulated patients diagnosed with stroke or transient ischaemic attack shared similar disease and outcome characteristics irrespective of anticoagulants used. One-third of warfarin patients with sub-therapeutic international normalised ratios were treated with thrombolytics but no direct oral anticoagulants level was performed in any of the patients, with only one treated by intravenous thrombolysis.

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“…No bleeding complications were observed. Only two out of 12 patients with ICH showed hematoma growth and the mortality rate was low (6.5%) 41. An interim analysis of an ongoing, phase III trial of idarucizumab in dabigatran‐treated adult patients with life‐threatening or uncontrolled bleeding, or in whom emergency surgery or an urgent procedure is required, demonstrated complete reversal of the anticoagulant effects of dabigatran as measured by dTT and ECT, and with no safety concerns 16, 17.…”

Section: Discussionmentioning

confidence: 99%

“…growth and the mortality rate was low (6.5%). 41 An interim analysis of an ongoing, phase III trial of idarucizumab in dabigatran-treated adult patients with life-threatening or uncontrolled bleeding, or in whom emergency surgery or an urgent procedure is required, demonstrated complete reversal of the anticoagulant effects of dabigatran as measured by dTT and ECT, and with no safety concerns. 16,17 Idarucizumab is specific for dabigatran reversal; antithrombotic therapy with unfractionated heparin or LMWH can therefore be started at any time after the surgery if the patient is stable and ongoing anticoagulation after the surgery is possible.…”

Section: Discussionmentioning

confidence: 99%

Rationale and design of a phase III safety trial of idarucizumab in children receiving dabigatran etexilate for venous thromboembolism

Albisetti¹,

Schlosser²,

Brueckmann³

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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Essentials There is no data on the use of idarucizumab in children with venous thromboembolism (VTE).We present the design of a trial that will assess the safety of idarucizumab in children with VTE.Patients will be recruited from two ongoing trials in children treated with dabigatran for VTE.Idarucizumab provides additional re‐assurance when rapid reversal of dabigatran effects is needed. BackgroundThe incidence of venous thromboembolism (VTE) in children has been increasing. Anticoagulants are the mainstay of treatment but are associated with bleeding events that may be life‐threatening. Idarucizumab is a fragment antigen‐binding (fab) that provides immediate, complete, and sustained reversal of dabigatran's anticoagulant effects in adults.Objective and MethodsThis phase III, open‐label, single‐arm, multicenter, multinational trial will assess the safety of idarucizumab in children participating in two ongoing trials investigating dabigatran etexilate. Eligible patients will be children with VTE (aged 0–≤18 years; n = ~5) with life‐threatening or uncontrolled bleeding (group A), and children who require emergency surgery/urgent procedures for a condition other than bleeding (group B). Patients will receive idarucizumab up to 5 g as two consecutive intravenous infusions over 5‐10 minutes each, as two 10‐15‐minute drips or as two bolus injections (15 minutes apart) and will be monitored for 30 days. The primary endpoint will be the safety of idarucizumab assessed by the occurrence of drug‐related adverse events (including immune reactions) and all‐cause mortality. Secondary endpoints will be the reversal of dabigatran anticoagulant effects assessed by changes in diluted thrombin time and ecarin clotting time, time to achieve complete reversal and the duration of the reversal and bleeding severity (group A). The formation of antidrug antibodies at 30 days post‐dose and cessation of bleeding will also be assessed.ConclusionThis study will report the safety of idarucizumab in children with VTE who require rapid reversal of the anticoagulant effects of dabigatran. Clinical trial registration: NCT02815670.

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Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany – A national case collection

Cited by 86 publications

References 23 publications

Endovascular stroke treatment does not preclude high thrombolysis rates

Endovascular stroke treatment does not preclude high thrombolysis rates

Ischaemic stroke and transient ischaemic attack on anticoagulants: outcomes in the era of direct oral anticoagulants

Rationale and design of a phase III safety trial of idarucizumab in children receiving dabigatran etexilate for venous thromboembolism

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