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2.
J Neurol ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775933

RESUMO

BACKGROUND: Hematoma volume is a major pathophysiological hallmark of acute intracerebral hemorrhage (ICH). We investigated how the variance in functional outcome induced by the ICH volume is explained by neurological deficits at admission using a mediation model. METHODS: Patients with acute ICH treated in three tertiary stroke centers between January 2010 and April 2019 were retrospectively analyzed. Mediation analysis was performed to investigate the effect of ICH volume (0.8 ml (5% quantile) versus 130.6 ml (95% quantile)) on the risk of unfavorable functional outcome at discharge defined as modified Rankin Score (mRS) ≥ 3 with mediation through National Institutes of Health Stroke Scale (NIHSS) at admission. Multivariable regression was conducted to identify factors related to neurological improvement and deterioration. RESULTS: Three hundred thirty-eight patients were analyzed. One hundred twenty-one patients (36%) achieved mRS ≤ 3 at discharge. Mediation analysis showed that NIHSS on admission explained 30% [13%; 58%] of the ICH volume-induced variance in functional outcome at smaller ICH volume levels, and 14% [4%; 46%] at larger ICH volume levels. Higher ICH volume at admission and brainstem or intraventricular location of ICH were associated with neurological deterioration, while younger age, normotension, lower ICH volumes, and lobar location of ICH were predictors for neurological improvement. CONCLUSION: NIHSS at admission reflects 14% of the functional outcome at discharge for larger hematoma volumes and 30% for smaller hematoma volumes. These results underscore the importance of effects not reflected in NIHSS admission for the outcome of ICH patients such as secondary brain injury and early rehabilitation.

3.
Front Neurol ; 15: 1389283, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817549

RESUMO

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.

4.
Neurol Int ; 16(2): 327-333, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38525703

RESUMO

The number of published cases of presumed iatrogenic cerebral amyloid angiopathy (iCAA) due to the transmission of amyloid ß during neurosurgery is slowly rising. One of the potential ways of transmission is through a cadaveric dura mater graft (LYODURA) exposure during neurosurgery. This is a case of a 46-year-old female patient with no chronic conditions who presented with recurrent intracerebral haemorrhages (ICHs) without underlying vessel pathology. Four decades prior, the patient had a neurosurgical procedure with documented LYODURA transplantation. Brain biopsy confirmed CAA. This is a rare case of histologically proven iCAA after a documented LYODURA transplantation in childhood. Our case and already published iCAA cases emphasize the need for considering neurosurgery procedure history as important data in patients who present with ICH possibly related to CAA.

5.
CNS Drugs ; 38(3): 163-168, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38396232

RESUMO

Andexanet alfa is a specific reversal agent for factor Xa inhibitors with immediate reversal of their anticoagulant effect. Andexanet alfa is currently approved for use in patients treated with rivaroxaban and apixaban who have life-threatening or uncontrolled bleeding. New data from both controlled clinical trials and real-world experience are continuously being published, providing greater insight into the clinical characteristics of the drug, such as efficacy and safety. It is worth considering that andexanet alfa could be of benefit in a variety of different clinical scenarios where patients receiving treatment with apixaban and rivaroxaban (and endoxaban) have life-threatening conditions. These different clinical scenarios, which range from pre-treatment of urgent surgery, especially neurosurgical interventions, and concomitant use of andexanet alfa and prothrombin complex concentrate to onset of bleeding more than 6 h prior to admission, should be clarified as well as the issue of "low/high" dose of andexanet alfa and the need for baseline anti-Xa inhibitor levels measured by point-of-care testing. Finally, management of patients at high risk of thrombosis or recent arterial/venous thrombotic events needs to be further explored. In this current opinion, we address these urgent questions in the light of recent literature and clinical trial data.


Assuntos
Hemorragia , Rivaroxabana , Humanos , Rivaroxabana/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Fator Xa/uso terapêutico , Fator Xa/farmacologia , Inibidores do Fator Xa/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Anticoagulantes/uso terapêutico
6.
J Stroke Cerebrovasc Dis ; 33(5): 107641, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38395096

RESUMO

OBJECTIVES: Intravenous thrombolysis (IVT) is recommended in patients with ischemic stroke in the anterior and posterior circulation. Neurological outcomes due to posterior circulation strokes (PCS) without treatment remain poor. Our aim was to overview the literature on outcomes of IVT and conservative treatment in PCS, based on a systematic review and meta-analysis. METHODS: A systematic literature search was performed on February 27th 2023. Outcome measures included favorable functional outcome at 90 days (modified Rankin Scale [mRS] 0-2), mortality at 90 days, and symptomatic intracranial hemorrhages (sICH). Weighted averages with DerSimonian-Laird approach was used to analyze the data. Subgroup analyses by time window were performed: standard time window (<4.5 hours after symptom onset) and extended time window (>4.5 hours). Analyses were performed using R. RESULTS: Eight prospective and four retrospective cohort studies were included (n = 1589 patients); no studies with conservative treatment were eligible. The pooled weighted probability regarding favorable functional outcome after IVT was 63 % (95 %CI:0.45-0.78), for mortality 19 % (95 %CI:0.11-0.30), and for sICH 4 % (95 %CI:0.02-0.07). Subgroup analyses showed higher probabilities on achieving favorable functional outcomes for patients treated in the standard (77 %; 95 %CI:0.62-0.88) compared to the extended time window (38 %; 95 %CI:0.29-0.48) with RR = 1.93 (95 %CI:1.66-2.24). Lower probabilities regarding mortality at 90 days and sICH were seen in patients treated in standard compared to extended time window (RR = 0.42, 95 %CI:0.34-0.51 and RR = 0.27, 95 %CI:0.16-0.45, respectively). CONCLUSIONS: IVT in patients with PCS seems to be safe and effective in standard and extended time window. The effect of IVT is higher in the standard time window.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Fibrinolíticos/efeitos adversos , AVC Isquêmico/etiologia , Terapia Trombolítica/efeitos adversos , Estudos Retrospectivos , Estudos Prospectivos , Resultado do Tratamento , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Hemorragias Intracranianas/induzido quimicamente , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Trombectomia/efeitos adversos
7.
Int J Stroke ; 19(3): 314-321, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37700397

RESUMO

BACKGROUND: The transmission of amyloid ß (Aß) in humans leading to iatrogenic cerebral amyloid angiopathy (iCAA) is a novel concept with analogies to prion diseases. However, the number of published cases is low, and larger international studies are missing. AIMS: We aimed to build a large multinational collaboration on iCAA to better understand the clinical spectrum of affected patients. METHODS: We collected clinical data on patients with iCAA from Austria, Croatia, Italy, Slovenia, and Spain. Patients were included if they met the proposed Queen Square diagnostic criteria (QSC) for iCAA. In addition, we pooled data on disease onset, latency, and cerebrospinal fluid (CSF) biomarkers from previously published iCAA cases based on a systematic literature review. RESULTS: Twenty-seven patients (22% women) were included in this study. Of these, 19 (70%) met the criteria for probable and 8 (30%) for possible iCAA. Prior neurosurgical procedures were performed in all patients (93% brain surgery, 7% spinal surgery) at median age of 8 (interquartile range (IQR) = 4-18, range = 0-26 years) years. The median symptom latency was 39 years (IQR = 34-41, range = 28-49). The median age at symptom onset was 49 years (IQR = 43-55, range = 32-70). Twenty-one patients (78%) presented with intracranial hemorrhage and 3 (11%) with seizures. CONCLUSIONS: Our large international case series of patients with iCAA confirms a wide age boundary for the diagnosis of iCAA. Dissemination of awareness of this rare condition will help to identify more affected patients.


Assuntos
Angiopatia Amiloide Cerebral , Acidente Vascular Cerebral , Humanos , Feminino , Pré-Escolar , Criança , Adolescente , Pessoa de Meia-Idade , Masculino , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Angiopatia Amiloide Cerebral/diagnóstico , Hemorragias Intracranianas , Doença Iatrogênica , Hemorragia Cerebral , Imageamento por Ressonância Magnética
8.
Neurol Int ; 15(4): 1352-1358, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37987458

RESUMO

Here, we present a case series of four patients diagnosed with acute ischaemic stroke due to occlusion of the artery of Percheron (AOP), a rare stroke variant, observed in a single emergency centre within a three-month period. AOP occlusion is characterized by bilateral thalamic infarction with or without involvement of the mesencephalon. The presenting symptoms are diverse and not specific, but commonly include disturbance of consciousness, memory impairment, and vertical gaze palsy. In addition, due to the location of the infarction, imaging recognition is challenging and AOP occlusion often remains undiagnosed. This paper emphasizes the necessity of early recognition and appropriate management of AOP occlusion to significantly impact patient outcomes. Moreover, we argue that the condition might be more common than previously thought and that misdiagnosis or delay in diagnosis may lead to inappropriate treatment and potential failure to apply thrombolysis within the required timeframe.

9.
Neurol Int ; 15(3): 1191-1199, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37755365

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune blood disorder characterised by isolated severe thrombocytopenia. Arterial thrombotic events, such as acute ischaemic stroke (AIS), are rare complications. A 56-year-old woman with chronic ITP on eltrombopag and dexamethasone therapy presented to the emergency department due to AIS in the vertebrobasilar territory, and lower abdominal pain. The computed tomography (CT) scan of the head was unremarkable, whereas CT angiography revealed left vertebral artery occlusion. As the platelet count was sufficient, intravenous thrombolysis (IVT) was initiated. However, after 15 min, an anaphylactic reaction occurred, which was appropriately solved. Although the IVT was prematurely stopped, the NIHSS score improved from 7 to 2, and the follow-up head CT scan remained unremarkable. CT angiography of the thoracoabdominal aorta revealed multiple thrombi in the infrarenal aorta, inferior mesenteric artery (IMA), and left renal artery. The abdominal pain subsided after IVT, but recurred within 24 h. Repeated CT angiography showed ischaemia of the descending colon, with persistent IMA occlusion. After the hemicolectomy condition stabilised. Discrete left-sided ataxia and impaired sensation were the only neurological sequelae. We found two articles reporting only three patients with ITP who suffered AIS and were treated with IVT. A favourable outcome was observed in two cases, while one patient suffered an intracranial haemorrhage (ICH) and died. A review of AIS cases with undefined thrombocytopenia treated with IVT reported ICH in up to 6.8% of patients. Our case suggests that IVT for AIS may be effective in patients with ITP. Further data are needed to better clarify this issue.

10.
CNS Drugs ; 37(6): 477-487, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37133623

RESUMO

Andexanet alfa (AA) is a recombinant factor Xa competing for binding with factor Xa inhibitors, thereby reversing their anticoagulation effects. Since 2019, it has been approved for individuals under apixaban or rivaroxaban therapy suffering from life-threatening or uncontrolled bleeding. Apart from the pivotal trial, real-world data on the use of AA in daily clinics are scarce. We reviewed the current literature on patients with intracranial hemorrhage (ICH) and summarized the available evidence regarding several outcome parameters. On the basis of this evidence, we provide a standard operating procedure (SOP) for routine AA application. We searched PubMed and additional databases through 18 January 2023 for case reports, case series, studies, reviews, and guidelines. Data on hemostatic efficacy, in-hospital mortality, and thrombotic events were pooled and compared with the pivotal trial data. While hemostatic efficacy in world-wide clinical routine seems to be comparable to the pivotal trial, thrombotic events and in-hospital mortality appear to be substantially higher. Various confounding factors responsible for this finding such as exclusion and inclusion criteria resulting in a highly selected patient cohort within the controlled clinical trial have to be considered. The SOP provided should support physicians in patient selection for AA treatment as well as facilitate routine use and dosing. This review underlines the urgent need for more data from randomized trials to appreciate the benefit and safety profile of AA. Meanwhile, this SOP should help to improve frequency and quality of AA use in patients suffering from ICH while on apixaban or rivaroxaban treatment.


Assuntos
Inibidores do Fator Xa , Hemostáticos , Humanos , Anticoagulantes/uso terapêutico , Fator Xa/metabolismo , Inibidores do Fator Xa/farmacologia , Hemostáticos/uso terapêutico , Hemorragias Intracranianas/tratamento farmacológico , Proteínas Recombinantes , Rivaroxabana
11.
J Thromb Thrombolysis ; 55(3): 506-518, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36738375

RESUMO

BACKGROUND: Reversal of dabigatran anticoagulation activity using idarucizumab is indicated for individuals suffering from life-threatening or non-controlled bleeding and those in need of urgent operation or invasive intervention. Through idarucizumab application patients with acute ischemic stroke (AIS) may regain eligibility for intravenous thrombolysis (IVT) and patients with intracranial hemorrhage (ICH) may show less hematoma growth, thereby improving functional outcome in both groups. However, evidence is limited, and international guidelines contain heterogenous recommendations substantiating the need for the review of evidence and standard operating procedures (SOPs). MATERIALS AND METHODS: For our review, we searched PubMed for all published articles using idarucizumab and ischemic stroke/hemorrhagic stroke as keywords. Illustrating two clinical cases, we discuss the current literature and national guidelines. RESULTS: Our search retrieved 47 articles of which 8 case studies or series made public after 2020/2021, 28 reviews, 1 leading opinion article, 1 editorial and 10 guidelines. Summarizing the available evidence, idarucizumab application in stroke patients taking dabigatran results in decreased mortality rate and improved functional outcomes. Based on two clinical cases from our departments, we provide SOPs on how to deal with eligible patients in a time-efficient way, thereby reducing door-to-needle times in AIS and preventing early deterioration in ICH patients. CONCLUSION: Reversal of dabigatran with idarucizumab in stroke patients appears easy to manage, safe and beneficial. The SOPs aim to reassure stroke physicians to include dabigatran reversal into their daily clinical routine when dealing with patients presenting with ischemic or hemorrhagic stroke under dabigatran therapy.


Assuntos
Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Dabigatrana/uso terapêutico , Antitrombinas/uso terapêutico , Acidente Vascular Cerebral Hemorrágico/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Hemorragias Intracranianas/tratamento farmacológico
12.
CNS Drugs ; 37(2): 133-141, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36646983

RESUMO

BACKGROUND AND OBJECTIVE: Cerebral venous thrombosis (CVT) is a rare disease, and data regarding direct oral anticoagulant therapy are insufficient. Apixaban could have a safer profile than other direct oral anticoagulants. We present our case series of patients with CVT treated with apixaban and a systematic review of published real-world cases. METHODS: We described our series of patients with CVT treated with apixaban and searched PubMed for similar published cases with reported complete outcome data: recanalisation rate, recurrent CVT, modified Rankin score, intracranial haemorrhage, other bleedings and mortality. RESULTS: Four male patients (average age 43.5 years) with idiopathic CVT, who presented with a headache and/or seizure without neurological deficits/symptoms or cerebral infarcts/haemorrhage were treated with apixaban 5 mg twice daily for an average 28 months (18-46 months) and followed for on average 2.8 years. In two patients, a partial/complete recanalisation was achieved, there was no recurrent CVT, all patients achieved a modified Rankin score of 0, none experienced an intracranial haemorrhage, other bleedings or died. One patient, in whom anti-phospholipid syndrome was later diagnosed, had a recurrence of CVT after stopping apixaban. Our systematic review identified only 15 eligible patients (average age 39 years, 60% female). Partial/complete recanalisation was achieved in 74% of cases, there was no recurrent CVT, 95% achieved a modified Rankin score of ≤ 2, none experienced an intracranial haemorrhage, other bleedings or died. CONCLUSIONS: Our cases and the review of similar published cases, albeit obtained on a smaller scale, suggest that apixaban may be a safe and effective therapy for CVT. This assumption should be tested in a large randomised study.


Assuntos
Trombose Intracraniana , Trombose dos Seios Intracranianos , Trombose Venosa , Humanos , Masculino , Feminino , Adulto , Trombose Venosa/diagnóstico , Hemorragias Intracranianas , Hemorragia Cerebral , Anticoagulantes
13.
Angiology ; 74(4): 344-350, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35694739

RESUMO

Recurrent ischemic strokes (IS) in patients treated with direct oral anticoagulant agents (DOACs) are rare. Knowledge regarding the type of recurrent IS and predisposing factors is insufficient. We analyzed a cohort of 1001 patients (77.6 ± 9.2 years; females: 57.1%) with non-valvular atrial fibrillation (AF) treated with DOACs as part of secondary prevention after initial IS or transient ischemic attack. Cardiovascular risk factors, stroke etiology, and Fazekas score based on computed tomography images at the time of the initial IS were assessed. Low Fazekas scores were defined as 0 or 1 and high scores were 2 or 3. Recurrent IS occurred in 46 patients (4.6%, annual rate 1.6%) during the observation period (2.8 ± 1.8 years). Stroke was cardioembolic in 20 patients (43.5%), lacunar in 19 patients (37.5%) and large artery stroke in 6 patients (19.2%). Non-cardioembolic stroke was more common (75.0 vs 26.7%; P = .002) in patients with high Fazekas scores. Arterial hypertension was more frequent (P = .027) in patients with high (93.3%) vs low (68.8%) Fazekas scores. Recurrent IS was predominantly non-cardioembolic with higher Fazekas score and arterial hypertension as predisposing factors. The reported hypothesis-generating results regarding the clinical relevance of the Fazekas score should be further evaluated.


Assuntos
Fibrilação Atrial , Hipertensão , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Feminino , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações , Anticoagulantes/efeitos adversos , Ataque Isquêmico Transitório/induzido quimicamente , Hipertensão/complicações , Administração Oral
15.
J Thromb Thrombolysis ; 53(3): 607-615, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34657237

RESUMO

Prescribing anticoagulation therapy in very old (≥ 80-years) patients with atrial fibrillation (AF) is an emerging clinical issue, but current knowledge and recommendations are insufficient. We aimed to determine the efficacy and safety of direct oral anticoagulants (DOACs) in secondary stroke prevention in very old patients and to explore the related geriatric functional status of these patients. Three hundred fifty-three consecutive ≥ 80-year-old patients treated for transient ischemic attack (TIA) or ischemic stroke (IS) at the neurological clinic at UMC Ljubljana, who were prescribed DOACs for AF between December 2012 and May 2020, were included. Data regarding recurrent TIA/IS, major bleeds, intracranial hemorrhage (ICH) and death were collected. Data were descriptively compared with data from RCTs- including younger patients. Patients prescribed DOACs between January 2018 and May 2020 were contacted in December 2020, and their functional status was assessed using the Barthel index (BI). The efficacy of secondary stroke prevention with DOACs was comparable to RCTs for significantly younger patients. Major bleeds occurred more often, but most incidences were gastrointestinal, and the rate of ICH was comparable. Importantly, most patients were highly independent determined by BI. Overall, our real world results suggest that DOACs are as effective at preventing IS in secondary prevention in very old patients than in younger patients and that geriatric functional assessment could be a useful tool in the decision-making process.


Assuntos
Fibrilação Atrial , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Estado Funcional , Hemorragia/induzido quimicamente , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/tratamento farmacológico , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/prevenção & controle , Prevenção Secundária , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
16.
J Stroke Cerebrovasc Dis ; 31(2): 106260, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34933275

RESUMO

BACKGROUND: CAA is a heterogeneous group of diseases caused by Aß deposition in the vascular walls, often leading to lobar ICH and cognitive impairment. Although CAA is rare in younger patients, it has been associated with specific mutations as well as with other causes. CASE PRESENTATION: We present four cases of patients with CAA and recurrent ICH who have a history of severe TBI in childhood. CONCLUSION: Our cases as well as review of the literature suggest that a history of TBI in patients with genetic predispositions such as male sex may be associated with CAA in young persons.


Assuntos
Angiopatia Amiloide Cerebral , Traumatismos Craniocerebrais , Angiopatia Amiloide Cerebral/diagnóstico , Angiopatia Amiloide Cerebral/genética , Traumatismos Craniocerebrais/epidemiologia , Predisposição Genética para Doença , Humanos , Masculino
17.
Front Neurol ; 12: 727403, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899558

RESUMO

Background: Intracranial hemorrhage is a severe and possibly fatal consequence of anticoagulation therapy. Idarucizumab is used in dabigatran-treated patients suffering from intracranial hemorrhage (ICH) to reverse the anticoagulant effect of dabigatran. Systematic review of real-life mortality in these patients is missing. Objectives: A review of all published dabigatran-related ICH cases treated with idarucizumab was performed. We aimed to estimate in-hospital mortality rate in these patients. Method: We searched PubMed and Scopus for all published cases of ICH in idarucizumab/dabigatran-treated patients until May 15, 2021. The assessed outcome was in-hospital mortality. Results: We identified six eligible studies (case series) with 386 patients and 54 single case reports. In-hospital mortality rate was 11.4% in the case series and 9.7% in the case reports. Conclusions: Our analysis provides clinically relevant quantitative data regarding in-hospital mortality in idarucizumab/dabigatran-treated patients with ICH, which is estimated to be 9.7-11.4%.

18.
Front Neurol ; 12: 666086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149597

RESUMO

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.

19.
CNS Drugs ; 35(2): 233-242, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33548038

RESUMO

BACKGROUND: Idarucizumab reverses the anticoagulant dabigatran; it is recommended during intravenous thrombolysis treatment of dabigatran-treated patients with acute ischemic stroke (AIS) and in dabigatran-treated patients with intracranial hemorrhage (ICH). METHODS: Outcomes of consecutive idarucizumab/dabigatran-treated patients with intravenous thrombolysis-treated AIS (n = 22) were compared with consecutive similar intravenous thrombolysis-treated patients with AIS who were not anticoagulated (n = 182) [primary aim]; idarucizumab/dabigatran-treated patients with ICH (n = 13) were compared with patients with ICH who received the anticoagulants rivaroxaban or apixaban (n = 24) [secondary aim]. Efficacy was estimated by National Institutes of Health Stroke Scale score changes between admission and discharge and by the modified Rankin score after 3 months; safety was assessed by symptomatic ICH and mortality. RESULTS: Basal neurological impairment was similar in both idarucizumab/dabigatran-treated and control groups of patients with AIS and ICH. The idarucizumab/dabigatran-treated patients with AIS with subsequent intravenous thrombolysis showed a mean National Institutes of Health Stroke Scale improvement of 84% vs 68% in the control group (p < 0.05). A favorable outcome (modified Rankin score ≤ 2 after 3 months) was achieved significantly more frequently than in the control group (86% vs 57%; p < 0.05). The complication rate was similar in both groups. In patients with ICH, a positive functional outcome (modified Rankin score ≤ 3 after 3 months) was achieved more often in the idarucizumab/dabigatran-treated group than in the control group (70% vs 42%; p = 0.109). The complication rate was similar. CONCLUSIONS: Idarucizumab use in dabigatran-treated patients with AIS resulted in significantly more efficacious intravenous thrombolysis treatment and a non-significantly better outcome in dabigatran-treated patients with ICH compared with controls. There was no difference regarding complications.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Dabigatrana/administração & dosagem , Hemorragias Intracranianas/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Dabigatrana/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Resultado do Tratamento
20.
J Thromb Thrombolysis ; 51(1): 194-202, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32506363

RESUMO

Successful revascularization therapy is of paramount importance in patients suffering acute ischemic stroke (AIS). However, there is currently only limited evidence on revascularization outcomes for patients suffering AIS while treated with direct oral anticoagulants (DOACs). The aim of our study was to determine the efficacy and safety of intravenous thrombolysis (IVT) and mechanical reperfusion (MeR) in AIS patients taking DOACs, and compare them to randomized clinical trials (RCTs), which included patients without DOAC treatment. In an observational cohort study, we analyzed clinical and radiological outcomes following AIS for all consecutive patients on DOAC therapy treated by IVT or MeR, between 2013 and 2019, at the University Medical Center Ljubljana. Patients in the IVT group were on dabigatran treatment and have received idarucizumab as a reversal agent prior to IVT. Patients in the MeR group had a large vessel occlusion. The primary outcome of the study was efficiency, defined as significant improvement after recanalization (National Institutes of Health Stroke Scale (NIHSS) score improvement of ≥8 points after 24 h and modified Rankin Scale (mRS) ≤2 after 3 months) and safety, defined as occurrence of symptomatic intracerebral hemorrhage (SICH) and mortality. Fifty-one DOAC-treated patients with AIS were included. Nineteen dabigatran-treated patients received IVT after reversal by idarucizumab. Thirty-two patients with a large vessel occlusion (12 on dabigatran, 12 on rivaroxaban, and 8 on apixaban) received MeR. Median NIHSS at admission was 9 in the IVT group and 17 in the MeR group. A significant clinical improvement, 24 h after revascularization (median improvement of NIHSS ≥8), occurred in 84% of patients treated with IVT and 25% of patients treated with MeR. A favorable functional outcome after 3 months (modified Rankin Scale (mRS) ≤2) occurred in 84 % of patients treated with IVT and 44% of patients treated with MeR. SICH occurred in one patient (5%) in the IVT group, and in two patients (6%) in the MeR group. In summary, in our observational study of DOAC-treated AIS patients, the level of IVT efficiency was substantially better than in the RCTs. At the same time, the results of MeR treatment were on the same level as in non-DOAC AIS patients included in the RCTs. The observed safety of IVT and MeR treatment was similar to the RCTs. We propose that thrombi in patients on dabigatran may have increased susceptibility to IVT, thereby allowing for better clinical results.


Assuntos
Inibidores do Fator Xa/uso terapêutico , AVC Isquêmico/tratamento farmacológico , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Terapia Trombolítica/efeitos adversos , Resultado do Tratamento
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