Intravenous Thrombolysis in Patients with Acute Ischemic Stroke after a Reversal of Dabigatran Anticoagulation with Idarucizumab: A Real-World Clinical Experience

Šaňák, Daniel; Jakubíček, Stanislava; Černík, David; Herzig, Roman; Kunáš, Zdeněk; Mikulík, Robert; Ostrý, Svatopluk; Reif, Michal; Rohan, Vladimír; Tomek, Aleš; Veverka, Tomáš

doi:10.1016/j.jstrokecerebrovasdis.2018.05.004

Cited by 28 publications

(23 citation statements)

References 14 publications

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“…Among 463 articles identified from the initial literature search, 49 studies including 251 patients were eligible and included in the analysis ( 1 , 13 – 57 , 60 – 63 ) ( Figure 1 ). Forty-five studies provided individual patient data of 119 AIS patients ( 13 – 23 , 25 , 27 – 36 , 38 – 57 , 60 – 63 ), whereas four case-series reported results on overall 151 patients ( 1 , 24 , 26 , 37 ).…”

Section: Resultsmentioning

confidence: 99%

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Intravenous Thrombolysis After Dabigatran Reversal by Idarucizumab: A Systematic Review of the Literature

et al. 2021

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Background and Purpose: Idarucizumab achieves instant reversal of anticoagulation and enables intravenous thrombolysis (IVT) in dabigatran-treated acute ischemic stroke (AIS) patients. AIS in dabigatran-treated patients is a rare event, therefore the experience is limited. A review of all published cases was performed to evaluate the safety and effectiveness of this therapeutic strategy.Methods: We searched PubMed and Scopus for all published cases of IVT after reversal with idarucizumab in dabigatran-treated AIS patients. The outcomes were safety assessed by hemorhagic transformation (HT), symptomatic intracranial hemorrhage (SICH) and death, and efficacy assessed by National Institutes of Health Stroke Scale (NIHSS) reduction.Results: We identified 251 AIS patients (39,9% females) with an average age of 74 years. HT, SICH, and death were reported in 19 (7.6%), 9 (3.6%), and 21 (8.4%) patients, respectively. Patients experiencing HT presented with more severe strokes (median NIHSS on admission: 21 vs. 8, p < 0.001; OR: 1.12, 95% CI: 1.05–1.20). After IVT there was a significant NIHSS reduction of 6 points (IQR:3–10, p < 0.001) post-stroke and linear regression revealed a correlation of admission NIHSS to NIHSS reduction (p < 0.001).Conclusions: In this systematic review of all published cases of IVT in dabigatran-treated AIS patients after reversal with idarucizumab the rates of HT, SICH and mortality, as well as NIHSS reduction, were comparable with previous studies in non-anticoagulated patients. This provides reassuring evidence about the safety and efficacy of this therapeutic strategy.

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Section: Resultsmentioning

confidence: 99%

“…Four studies reported aggregate data for 151 patients who were treated with IVT after dabigatran reversal with idarucizumab ( 1 , 24 , 26 , 37 ). The baseline characteristics of each case series are summarized in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

Intravenous Thrombolysis After Dabigatran Reversal by Idarucizumab: A Systematic Review of the Literature

et al. 2021

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“…There is a considerable number of case-reports (25 case reports including 31 patients) and one large case series (80 patients) 52 using idarucizumab prior to IVT. Table 3 provides an overview about currently available data from observational studies (bottom paragraph, 'Idarucizumab': 8 studies including 236 patients) using idarucizumab, including national and hospital based data from continental Europe, [52][53][54][55] New Zealand 35 37 and Taiwan. 56 Idarucizumab 5 g infusion was administered without waiting for confirmation of postreversal normalisation of coagulation profile.…”

Section: Use Of Specific Reversal Agents Prior To Acute Treatmentmentioning

confidence: 99%

Recanalisation therapies for acute ischaemic stroke in patients on direct oral anticoagulants

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Purrucker

et al. 2021

J Neurol Neurosurg Psychiatry

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Direct oral anticoagulants (DOACs) have emerged as primary therapeutic option for stroke prevention in patients with atrial fibrillation. However, patients may have ischaemic stroke despite DOAC therapy and there is uncertainty whether those patients can safely receive intravenous thrombolysis or mechanical thrombectomy. In this review, we summarise and discuss current knowledge about different approaches to select patient. Time since last DOAC intake—as a surrogate for anticoagulant activity—is easy to use but limited by interindividual variability of drug pharmacokinetics and long cut-offs (>48 hours). Measuring anticoagulant activity using drug-specific coagulation assays showed promising safety results. Large proportion of patients at low anticoagulant activity seem to be potentially treatable but there remains uncertainty about exact safe cut-off values and limited assay availability. The use of specific reversal agents (ie, idarucizumab or andexanet alfa) prior to thrombolysis is a new emerging option with first data reporting safety but issues including health economics need to be elucidated. Mechanical thrombectomy appears to be safe without any specific selection criteria applied. In patients on DOAC therapy with large vessel occlusion, decision for intravenous thrombolysis should not delay thrombectomy (eg, direct thrombectomy or immediate transfer to a thrombectomy-capable centre recommended). Precision medicine using a tailored approach combining clinicoradiological information (ie, penumbra and vessel status), anticoagulant activity and use of specific reversal agents only if necessary seems a reasonable choice.

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“…More frequent use, however, of NOACs itself poses new challenges in patients subsequently suffering from stroke. While on NOACs, thrombolytic treatment is usually contraindicated ( Tsivgoulis and Safouris, 2017 ; Šaňák et al, 2018 ; Shahjouei et al, 2020 ; Tsivgoulis et al, 2021 ). The only alternative, mechanical thrombectomy, is however, suitable only for patients with large vessel occlusion and is not universally available ( Šaňák et al, 2018 ; Shahjouei et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…While on NOACs, thrombolytic treatment is usually contraindicated ( Tsivgoulis and Safouris, 2017 ; Šaňák et al, 2018 ; Shahjouei et al, 2020 ; Tsivgoulis et al, 2021 ). The only alternative, mechanical thrombectomy, is however, suitable only for patients with large vessel occlusion and is not universally available ( Šaňák et al, 2018 ; Shahjouei et al, 2020 ). Idarucizumab is an antidote that allows thrombolysis in patients on dabigatran ( Šaňák et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Apixaban Pretreatment on Alteplase-Induced Thrombolysis: An In Vitro Study

et al. 2021

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Benefit of thrombolytic therapy in patients with acute stroke, who are on anticoagulant treatment, is not well addressed. The aim of this study was to investigate whether apixaban can modify the thrombolytic efficacy of alteplase in vitro. Static and flow models and two variants of red blood cell (RBC) dominant clots, with and without apixaban, were used. Clots were prepared from the blood of healthy human donors and subsequently exposed to alteplase treatment. Apixaban and alteplase were used in clinically relevant concentrations. Clot lysis in the static model was determined both by clot weight and spectrophotometric determination of RBC release. Clot lysis in the flow model was determined by measuring recanalization time, clot length and spectrophotometric determination of RBC release. In the static model, clots without apixaban; compared to those with apixaban had alteplase-induced mass loss 54 ± 8% vs. 53 ± 8%, p = 1.00; RBC release 0.14 ± 0.04 vs. 0.12 ± 0.04, p = 0.14, respectively. Very similar results were obtained if plasma was used instead of physiological buffered saline as the incubation medium. In the flow model, clot lysis without apixaban; compared to those with apixaban was as follows: recanalization time 107 ± 46 min vs. 127 ± 31 min, p = 1.00; recanalization frequency 90 ± 22% vs. 90 ± 22%, p = 1.00; clot volume reduction 32 ± 15% vs. 34 ± 10%, p = 1.00; RBC release 0.029 ± 0.007 vs. 0.022 ± 0.007, p = 0.16, respectively. Apixaban had no positive effect on alteplase-induced thrombolysis in both the in vitro static and flow models. Our data support current clinical practice, such that thrombolysis is contraindicated in stroke treatment for patients who have been treated with anticoagulants.

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Intravenous Thrombolysis in Patients with Acute Ischemic Stroke after a Reversal of Dabigatran Anticoagulation with Idarucizumab: A Real-World Clinical Experience

Cited by 28 publications

References 14 publications

Intravenous Thrombolysis After Dabigatran Reversal by Idarucizumab: A Systematic Review of the Literature

Intravenous Thrombolysis After Dabigatran Reversal by Idarucizumab: A Systematic Review of the Literature

Recanalisation therapies for acute ischaemic stroke in patients on direct oral anticoagulants

Effect of Apixaban Pretreatment on Alteplase-Induced Thrombolysis: An In Vitro Study

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