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1. Safety and efficacy of prophylactic levetiracetam for prevention of epileptic seizures in the acute phase of intracerebral haemorrhage (PEACH): a randomised, double-blind, placebo-controlled, phase 3 trial.

Author

Peter-Derex L, Philippeau F, Garnier P, André-Obadia N, Boulogne S, Catenoix H, Convers P, Mazzola L, Gouttard M, Esteban M, Fontaine J, Mechtouff L, Ong E, Cho TH, Nighoghossian N, Perreton N, Termoz A, Haesebaert J, Schott AM, Rabilloud M, Pivot C, Dhelens C, Filip A, Berthezène Y, Rheims S, Boutitie F, and Derex L

Subjects
Cerebral Hemorrhage complications, Cerebral Hemorrhage drug therapy, Humans, Levetiracetam adverse effects, Seizures complications, Seizures drug therapy, Seizures prevention & control, Treatment Outcome, United States, Epilepsy complications, Stroke drug therapy
Abstract

Background: The incidence of early seizures (occurring within 7 days of stroke onset) after intracerebral haemorrhage reaches 30% when subclinical seizures are diagnosed by continuous EEG. Early seizures might be associated with haematoma expansion and worse neurological outcomes. Current guidelines do not recommend prophylactic antiseizure treatment in this setting. We aimed to assess whether prophylactic levetiracetam would reduce the risk of acute seizures in patients with intracerebral haemorrhage., Methods: The double-blind, randomised, placebo-controlled, phase 3 PEACH trial was conducted at three stroke units in France. Patients (aged 18 years or older) who presented with a non-traumatic intracerebral haemorrhage within 24 h after onset were randomly assigned (1:1) to levetiracetam (intravenous 500 mg every 12 h) or matching placebo. Randomisation was done with a web-based system and stratified by centre and National Institutes of Health Stroke Scale (NIHSS) score at baseline. Treatment was continued for 6 weeks. Continuous EEG was started within 24 h after inclusion and recorded over 48 h. The primary endpoint was the occurrence of at least one clinical seizure within 72 h of inclusion or at least one electrographic seizure recorded on continuous EEG, analysed in the modified intention-to-treat population, which comprised all patients who were randomly assigned to treatment and who had a continuous EEG performed. This trial was registered at ClinicalTrials.gov, NCT02631759, and is now closed. Recruitment was prematurely stopped after 48% of the recruitment target was reached due to a low recruitment rate and cessation of funding., Findings: Between June 1, 2017, and April 14, 2020, 50 patients with mild-to-moderate severity intracerebral haemorrhage were included: 24 were assigned to levetiracetam and 26 to placebo. During the first 72 h, a clinical or electrographic seizure was observed in three (16%) of 19 patients in the levetiracetam group versus ten (43%) of 23 patients in the placebo group (odds ratio 0·16, 95% CI 0·03-0·94, p=0·043). All seizures in the first 72 h were electrographic seizures only. No difference in depression or anxiety reporting was observed between the groups at 1 month or 3 months. Depression was recorded in three (13%) patients who received levetiracetam versus four (15%) patients who received placebo, and anxiety was reported for two (8%) patients versus one (4%) patient. The most common treatment-emergent adverse events in the levetiracetam group versus the placebo group were headache (nine [39%] vs six [24%]), pain (three [13%] vs ten [40%]), and falls (seven [30%] vs four [16%]). The most frequent serious adverse events were neurological deterioration due to the intracerebral haemorrhage (one [4%] vs four [16%]) and severe pneumonia (two [9%] vs two [8%]). No treatment-related death was reported in either group., Interpretation: Levetiracetam might be effective in preventing acute seizures in intracerebral haemorrhage. Larger studies are needed to determine whether seizure prophylaxis improves functional outcome in patients with intracerebral haemorrhage., Funding: French Ministry of Health., Competing Interests: Declarations of interests LP-D reports speaker's honoraria and travel fees from Bioprojet, Jazz Pharmaceuticals, Roche, and UCB. SB reports speaker's honoraria and travel fees from ESAI, Livanona, UCB, and Angelini Pharma. SR reports speaker's honoraria and travel fees from UCB, ESAI, Angelini Pharma, Zogenix, and Gaoma Therapeutics. LD reports speaker's honoraria and travel fees from Alexion, Boehringer Ingelheim, Pfizer, and Servier. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Published
2022
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2. Prediction of Early Neurological Deterioration in Individuals With Minor Stroke and Large Vessel Occlusion Intended for Intravenous Thrombolysis Alone.

Author

Seners P, Ben Hassen W, Lapergue B, Arquizan C, Heldner MR, Henon H, Perrin C, Strambo D, Cottier JP, Sablot D, Girard Buttaz I, Tamazyan R, Preterre C, Agius P, Laksiri N, Mechtouff L, Béjot Y, Duong DL, Mounier-Vehier F, Mione G, Rosso C, Lucas L, Papassin J, Aignatoaie A, Triquenot A, Carrera E, Niclot P, Obadia A, Lyoubi A, Garnier P, Crainic N, Wolff V, Tracol C, Philippeau F, Lamy C, Soize S, Baron JC, and Turc G

Subjects
Administration, Intravenous methods, Aged, Aged, 80 and over, Cerebrovascular Disorders diagnostic imaging, Cerebrovascular Disorders epidemiology, Cohort Studies, Female, Fibrinolytic Agents administration & dosage, Humans, Male, Mechanical Thrombolysis methods, Middle Aged, Nervous System Diseases diagnostic imaging, Nervous System Diseases epidemiology, Nervous System Diseases therapy, Predictive Value of Tests, Retrospective Studies, Stroke diagnostic imaging, Stroke epidemiology, Thrombolytic Therapy methods, Administration, Intravenous trends, Cerebrovascular Disorders therapy, Mechanical Thrombolysis trends, Stroke therapy, Thrombolytic Therapy trends, Tissue Plasminogen Activator administration & dosage
Abstract

Importance: The best reperfusion strategy in patients with acute minor stroke and large vessel occlusion (LVO) is unknown. Accurately predicting early neurological deterioration of presumed ischemic origin (ENDi) following intravenous thrombolysis (IVT) in this population may help to select candidates for immediate transfer for additional thrombectomy., Objective: To develop and validate an easily applicable predictive score of ENDi following IVT in patients with minor stroke and LVO., Design, Setting, and Participants: This multicentric retrospective cohort included 729 consecutive patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score of 5 or less) and LVO (basilar artery, internal carotid artery, first [M1] or second [M2] segment of middle cerebral artery) intended for IVT alone in 45 French stroke centers, ie, including those who eventually received rescue thrombectomy because of ENDi. For external validation, another cohort of 347 patients with similar inclusion criteria was collected from 9 additional centers. Data were collected from January 2018 to September 2019., Main Outcomes and Measures: ENDi, defined as 4 or more points' deterioration on NIHSS score within the first 24 hours without parenchymal hemorrhage on follow-up imaging or another identified cause., Results: Of the 729 patients in the derivation cohort, 335 (46.0%) were male, and the mean (SD) age was 70 (15) years; of the 347 patients in the validation cohort, 190 (54.8%) were male, and the mean (SD) age was 69 (15) years. In the derivation cohort, the median (interquartile range) NIHSS score was 3 (1-4), and the occlusion site was the internal carotid artery in 97 patients (13.3%), M1 in 207 (28.4%), M2 in 395 (54.2%), and basilar artery in 30 (4.1%). ENDi occurred in 88 patients (12.1%; 95% CI, 9.7-14.4) and was strongly associated with poorer 3-month outcomes, even in patients who underwent rescue thrombectomy. In multivariable analysis, a more proximal occlusion site and a longer thrombus were independently associated with ENDi. A 4-point score derived from these variables-1 point for thrombus length and 3 points for occlusion site-showed good discriminative power for ENDi (C statistic = 0.76; 95% CI, 0.70-0.82) and was successfully validated in the validation cohort (ENDi rate, 11.0% [38 of 347]; C statistic = 0.78; 95% CI, 0.70-0.86). In both cohorts, ENDi probability was approximately 3%, 7%, 20%, and 35% for scores of 0, 1, 2 and 3 to 4, respectively., Conclusions and Relevance: The substantial ENDi rates observed in these cohorts highlights the current debate regarding whether to directly transfer patients with IVT-treated minor stroke and LVO for additional thrombectomy. Based on the strong associations observed, an easily applicable score for ENDi risk prediction that may assist decision-making was derived and externally validated.

Published
2021
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3. Cyclosporine in acute ischemic stroke.

Author

Nighoghossian N, Berthezène Y, Mechtouff L, Derex L, Cho TH, Ritzenthaler T, Rheims S, Chauveau F, Béjot Y, Jacquin A, Giroud M, Ricolfi F, Philippeau F, Lamy C, Turc G, Bodiguel E, Domigo V, Guiraud V, Mas JL, Oppenheim C, Amarenco P, Cakmak S, Sevin-Allouet M, Guillon B, Desal H, Hosseini H, Sibon I, Mahagne MH, Ong E, Mewton N, and Ovize M

Subjects
Aged, Aged, 80 and over, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Male, Middle Aged, Pilot Projects, Single-Blind Method, Brain Ischemia diagnosis, Brain Ischemia drug therapy, Cyclosporine administration & dosage, Stroke diagnosis, Stroke drug therapy, Thrombolytic Therapy trends
Abstract

Objectives: We examined whether IV administration of cyclosporine in combination with thrombolysis might reduce cerebral infarct size., Methods: Patients aged 18 to 85 years, presenting with an anterior-circulation stroke and eligible for thrombolytic therapy, were enrolled in this multicenter, single-blinded, controlled trial. Fifteen minutes after randomization, patients received either an IV bolus injection of 2.0 mg/kg cyclosporine (Sandimmune, Novartis) or placebo. The primary endpoint was infarct volume on MRI at 30 days. Secondary endpoints included infarct volume according to the site (proximal/distal) of arterial occlusion and recanalization after thrombolysis., Results: From October 2009 to July 2013, 127 patients were enrolled. The primary endpoint was assessed in 110 of 127 patients. The reduction of infarct volume in the cyclosporine compared with the control group was overall not significant (21.8 mL [interquartile range, IQR 5.1, 69.2 mL] vs 28.8 mL [IQR 7.7, 95.0 mL], respectively; p = 0.18). However, in patients with proximal occlusion and effective recanalization, infarct volume was significantly reduced in the cyclosporine compared with the control group (14.9 mL [IQR 1.3, 23.2 mL] vs 48.3 mL [IQR 34.5, 118.2 mL], respectively; p = 0.009)., Conclusions: Cyclosporine was generally not effective in reducing infarct size. However, a smaller infarct size was observed in patients with proximal cerebral artery occlusion and efficient recanalization., Classification of Evidence: This study provides Class I evidence that in patients with an acute anterior-circulation stroke, thrombolysis plus IV cyclosporine does not significantly decrease 30-day MRI infarct volume compared with thrombolysis alone., (© 2015 American Academy of Neurology.)

Published
2015
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4. Thrombolysis for Acute Minor Stroke: Outcome and Barriers to Management. Results from the RESUVAL Stroke Network.

Author

Laurencin C, Philippeau F, Blanc-Lasserre K, Vallet AE, Cakmak S, Mechtouff L, Cho TH, Ritzenthaler T, Flocard E, Bischoff M, El Khoury C, Nighoghossian N, and Derex L

Subjects
Aged, Aged, 80 and over, Cerebral Hemorrhage chemically induced, Diagnostic Imaging methods, Disability Evaluation, Female, Fibrinolytic Agents adverse effects, France, Humans, Infusions, Intravenous, Male, Middle Aged, Patient Admission, Registries, Retrospective Studies, Risk Factors, Severity of Illness Index, Stroke diagnosis, Time Factors, Time-to-Treatment, Tissue Plasminogen Activator adverse effects, Transportation of Patients, Treatment Outcome, Fibrinolytic Agents administration & dosage, Stroke drug therapy, Thrombolytic Therapy adverse effects, Tissue Plasminogen Activator administration & dosage
Abstract

Background: We evaluated the management, outcome and haemorrhagic risk in a cohort of ischaemic stroke patients with mild symptoms treated with intravenous tissue plasminogen activator (tPA) within the first 4.5 h., Methods: We analysed data from a prospective stroke thrombolysis registry. A total of 1,043 patients received tPA between 2010 and 2014 in the 5 stroke units of the RESUVAL stroke network (Rhône Valley, France). Among them, 170 patients had a National Institute of Health Stroke Scale (NIHSS) score ≤4 (minor group: MG) before tPA and 873 patients had a NIHSS score >4., Results: A high rate (77%) of excellent outcome (3-month-modified Rankin Scale score ≤1) was observed in the MG. No symptomatic intracerebral haemorrhage occurred and the rate of any haemorrhagic transformation was 5%. Fifty-four percent of the MG patients had visible arterial occlusion before tPA. Patients of the MG were less likely to be transported by Emergency Medical Services and to be directly admitted to the stroke unit or to imaging. Median delays from onset to admission, from admission to imaging and from onset to tPA were longer in the MG., Conclusion: Our data provided evidence of safety and suggested potential benefit of thrombolysis in patients with NIHSS score ≤4. A majority of these patients exhibited arterial occlusion before thrombolysis. Most often, patients with mild stroke are not given priority in terms of the mode of transport, direct admission to stroke unit and rapid imaging, resulting in an increased delay from onset to thrombolysis. Health system improvements are needed to provide all suspected stroke victims equal access to imaging and treatment on an emergency basis.

Published
2015
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5. Audit report and systematic review of orolingual angioedema in post-acute stroke thrombolysis.

Author

Lekoubou A, Philippeau F, Derex L, Olaru A, Gouttard M, Vieillart A, and Kengne AP

Subjects
Angioedema drug therapy, Angioedema epidemiology, Fibrinolytic Agents therapeutic use, France epidemiology, Hospitals, General, Humans, Incidence, Medical Audit, Mouth Diseases chemically induced, Mouth Diseases drug therapy, Mouth Diseases epidemiology, Observational Studies as Topic, Recombinant Proteins adverse effects, Recombinant Proteins therapeutic use, Tissue Plasminogen Activator therapeutic use, Angioedema chemically induced, Brain Ischemia drug therapy, Fibrinolytic Agents adverse effects, Stroke drug therapy, Thrombolytic Therapy adverse effects, Tissue Plasminogen Activator adverse effects
Abstract

Rationale: Post-intravenous recombinant tissue plasminogen activator (r-tPA) orolingual angioedema (PIROLA), including the life-threatening form, is an underappreciated complication of ischaemic stroke treatment., Aims: We present an audit report and a systematic review of published observational studies on PIROLA occurrence in acute ischaemic stroke patients., Methods: Clinical files of patients treated in the stroke unit of Bourg-en-Bresse General Hospital (France) from January 2010 to December 2012 were reviewed, and MEDLINE (inception to May 2013) were searched and bibliographies/citations of retrieved articles examined for evidence of PIROLA., Results: Of the 129 acute ischaemic stroke patients treated at Bourg-en-Bresse between 2010 and 2012, four patients, all receiving angiotensin converting enzyme inhibitor (ACEI), developed a PIROLA (cumulative incidence rate: 32‰). The complication started within an hour of receiving r-tPA and integrally resolved within 3-24 hours, with antihistamines/steroid treatment in two patients. The systematic review identified 27 studies, totalising with ours, over 9050 acute ischaemic stroke patients from 12 countries, among whom 100 (cumulative incidence rate: 17‰; 95% confidence intervals: 8-26), developed a PIROLA within 6-240 minutes of receiving r-tPA, 0-100% of them occurring among patients on ACEI. The complication was contralateral to the stroke location in 47% cases, ipsilateral in 14%, and bilateral in 39%; and resolved within 24 hours with treatment in 90%. No related death was recorded., Conclusions: About 17‰ acute ischaemic stroke patients receiving r-tPA develop PIROLA, occurring essentially among those on concomitant ACEI. PIROLA occurrence should be actively monitored, particularly within the first few hours as some may require urgent lifesaving procedures.

Published
2014
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6. Ethical issues of informed consent in acute stroke. Analysis of the modalities of consent in 56 patients enrolled in urgent therapeutic trials.

Author

Demarquay G, Derex L, Nighoghossian N, Adeleine P, Philippeau F, Honnorat J, and Trouillas P

Subjects
Adult, Aged, Aged, 80 and over, Decision Making ethics, Family psychology, Female, Humans, Informed Consent psychology, Male, Middle Aged, Stroke psychology, Health Knowledge, Attitudes, Practice, Informed Consent ethics, Mental Competency, Randomized Controlled Trials as Topic ethics, Stroke therapy
Abstract

Background: Many patients may be mentally incompetent or physically unable to give informed consent at the acute stage of stroke. Accordingly, we aimed to investigate the modalities of informed consent in urgent therapeutic stroke trials, the awareness of patients and relatives regarding stroke clinical trials and the impact of decision making on patients and relatives., Methods: We present a study of 56 acute ischemic stroke patients who were randomized in 4 trials (2 trials testing neuroprotective agents, 1 testing thrombolysis and 1 testing antithrombotic agents). A standardized questionnaire was used to assess the modalities of informed consent in this setting., Results: The mean age was 67.1 (SD 12.6) years. The mean baseline Scandinavian Stroke Scale (SSS) score was 23.8 (SD 10.5). Only 13 patients (23% of cases) gave consent while relatives gave consent for 43 patients (77%). The main reason for not getting consent from the patient was aphasia in 29 patients (67.4%). Multiple logistic regression analysis showed that the two independent factors influencing the ability to give consent are age and baseline neurological deficit as assessed by the SSS score. Concerning the psychological impact of consent, none of the 10 patients who answered our questionnaire declared feeling uncomfortable when giving consent, while 7 out of the 13 relatives who could be reached declared they felt uncomfortable, mainly because of the psychological stress induced by urgent decision making., Conclusions: Our study emphasizes the specific ethical difficulties of informed consent in the setting of acute stroke research. Only a minority of patients are able to give consent at the acute stage. Increasing age and neurological deficit are independent predictors of inability to give consent. Thus, the responsibility for consent usually relies on relatives with potential inaccuracy of decision concerning the patient's wish or even conflict of interest. Further evaluation of the psychological impact of decision on relatives is needed in this setting of acute stroke., (Copyright (c) 2005 S. Karger AG, Basel.)

Published
2005
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7. Influence of pretreatment MRI parameters on clinical outcome, recanalization and infarct size in 49 stroke patients treated by intravenous tissue plasminogen activator.

Author

Derex L, Nighoghossian N, Hermier M, Adeleine P, Berthezène Y, Philippeau F, Honnorat J, Froment JC, and Trouillas P

Subjects
Adult, Aged, Aged, 80 and over, Analysis of Variance, Brain Infarction diagnosis, Brain Mapping, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Reproducibility of Results, Retrospective Studies, Stroke complications, Time Factors, Tomography, X-Ray Computed methods, Trauma Severity Indices, Treatment Outcome, Brain Infarction etiology, Stroke diagnosis, Stroke drug therapy, Tissue Plasminogen Activator therapeutic use
Abstract

We hypothesized that pretreatment magnetic resonance imaging (MRI) parameters might predict clinical outcome, recanalization and final infarct size in acute ischemic stroke patients treated by intravenous recombinant tissue plasminogen activator (rt-PA). MRI was performed prior to thrombolysis and at day 1 with the following sequences: magnetic resonance angiography (MRA), T2*-gradient echo (GE) imaging, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). Final infarct size was assessed at day 60 by T2-weighted imaging (T2-WI). The National Institutes of Health Stroke Scale (NIHSS) score was assessed prior to rt-PA therapy and the modified Rankin Scale (m-RS) score was assessed at day 60. A poor outcome was defined as a day 60 m-RS score >2. Univariate and multivariate logistic regression analyses were used to identify the predictors of clinical outcome, recanalization and infarct size. Forty-nine patients fulfilled the inclusion criteria. Baseline NIHSS score was the best independent indicator of clinical outcome (p=0.002). A worse clinical outcome was observed in patients with tandem internal carotid artery (ICA)+middle cerebral artery (MCA) occlusion versus other sites of arterial occlusion (p=0.009), and in patients with larger pretreatment PWI (p=0.001) and DWI (p=0.01) lesion volumes. Two factors predict a low rate of recanalization: a proximal site of arterial occlusion (p=0.02) and a delayed time to peak (TTP) on pretreatment PWI (p=0.05). The final infarct size was correlated with pretreatment DWI lesion volume (p=0.025). Recanalization was associated with a lower final infarct size (p=0.003). In conclusion, a severe baseline NIHSS score, a critical level of pretreatment DWI/PWI parameters and a proximal site of occlusion are predictive of a worse outcome after IV rt-PA for acute ischemic stroke.

Published
2004
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8. Early magnetic resonance imaging prediction of arterial recanalization and late infarct volume in acute carotid artery stroke.

Author

Hermier M, Nighoghossian N, Adeleine P, Berthezène Y, Derex L, Yilmaz H, Dugor JF, Dardel P, Cotton F, Philippeau F, Trouillas P, and Froment JC

Subjects
Acute Disease, Aged, Cerebral Infarction etiology, Female, Forecasting, Humans, Magnetic Resonance Angiography, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Stroke etiology, Stroke physiopathology, Time Factors, Treatment Outcome, Carotid Artery Diseases complications, Cerebral Arteries physiopathology, Cerebral Infarction diagnosis, Magnetic Resonance Imaging, Stroke diagnosis, Stroke therapy, Thrombolytic Therapy
Abstract

In patients with acute ischemic stroke, early recanalization may save tissue at risk for ischemic infarction, thus resulting in smaller infarcts and better clinical outcome. The hypothesis that clinical and diffusion- and perfusion-weighted imaging (DWI, PWI) parameters may have a predictive value for early recanalization and final infarct size was assessed. Twenty-nine patients were prospectively enrolled and underwent sequential magnetic resonance imaging (1) within 6 hours from hemispheric stroke onset, before thrombolytic therapy; (2) at day 1; and (3) at day 60. Late infarct volume was assessed by T2 -weighted imaging. At each time, clinical status was assessed by the National Institutes of Health Stroke Scale (NIHSS). Twenty-eight patients had arterial occlusion at day 0 magnetic resonance angiography (MRA). They were classified into two groups according to day 1 MRA: recanalization (n = 18) versus persistent occlusion (n = 10). Any significant differences between these groups were assessed regarding (1) PWI and DWI abnormality volumes, (2) relative and absolute time-to-peak (TTP) and apparent diffusion coefficient within the lesion on DWI; and (3) day 60 lesion volume on T2 -weighted imaging. Univariate and multivariate logistic regression analysis showed that the most powerful predictive factors for recanalization were lower baseline NIHSS score and lower baseline absolute TTP within the lesion on DWI. The best predictors of late infarct size were day 0 lesion volume on DWI and day 1 recanalization. Early PWI and DWI studies and day 1 MRA provide relevant predictive information on stroke outcome.

Published
2003
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9. Effect of Operator's Experience on Proficiency in Mechanical Thrombectomy: A Multicenter Study

Author

François Zhu, Wagih Ben Hassen, Nicolas Bricout, Basile Kerleroux, Kevin Janot, Benjamin Gory, René Anxionnat, Sébastien Richard, Adrien Marchal, Raphael Blanc, Michel Piotin, Arturo Consoli, Denis Trystram, Christine Rodriguez Regent, Jean-Philippe Desilles, David Weisenburger-Lile, Simon Escalard, Denis Herbreteau, Heloise Ifergan, Igor Lima Maldonado, Julien Labreuche, Hilde Henon, Olivier Naggara, Bertrand Lapergue, Grégoire Boulouis, Redjem Hocine, Ciccio Gabriele, Smajda Stanislas, Maier Benjamin, Mazighi Mikael, Obadia Mikael, Sabben Candice, Peres Roxanne, Corabianu Ovide, De Broucker Thomas, Smadja Didier, Alamowitch Sonia, Ille Olivier, Manchon Eric, Garcia Pierre-Yves, Taylor Guillaume, Ben Maacha Malek, Wang Adrien, Evrard Serge, Tchikviladze Maya, Ajili Nadia, Gorza Lucas, Buard Géraldine, Coskun Oguzhan, Di Maria Federico, Rodesh Georges, Zimatore Sergio, Leguen Morgan, Gratieux Julie, Pico Fernando, Rakotoharinandrasana Haja, Tassan Philippe, Poll Roxanna, Marinier Sylvie, Nighoghossian Norbert, Riva Roberto, Eker Omer, Turjman Francis, Derex Laurent, Cho Tae-Hee, Mechtouff Laura, Claire Lukaszewicz Anne, Philippeau Frédéric, Cakmak Serkan, Blanc-Lasserre Karine, Vallet Anne-Evelyne, Marnat Gaultier, Gariel Florent, Barreau Xavier, Berge Jérôme, Menegon Patrice, Sibon Igor, Liegey Sebastien, Olindo Stéphane, Renou Pauline, Sagnier Sharmila, Poli Mathilde, Debruxelles Sabrina, Pangon Nicolas, Bourcier Romain, Detraz Lili, Daumas-Duport Benjamin, Alexandre Pierre-Louis, Roy Monica, Lenoble Cédric, L’allinec Vincent, Girot Jean-Baptiste, Desal Hubert, Bracard Serge, Braun Marc, Derelle Anne-Laure, Tonnelet Romain, Liao Liang, Muszynski Patricio, Schmitt Emmanuelle, Planel Sophie, Humbertjean Lisa, Mione Gioia, Lacour Jean-Christophe, Riou-Comte Nolwenn, Audibert Gérard, Voicu Marcela, Alb Ionel, Reitter Marie, Brezeanu Madalina, Masson Agnès, Tabarna Adriana, Podar Ioana, Macian-Montoro Francisco, Saleme Suzanna, Mounayer Charbel, Rouchaud Aymeric, Costalat Vincent, Arquizan Caroline, Dargazanli Cyril, Gascou Grégory, Lefèvre Pierre-Henri, Derraz Imad, Riquelme Carlos, Gaillard Nicolas, Mourand Isabelle, Corti Lucas, Francois Eugene, Vannier Stéphane, Ferre Jean-Christophe, Raoult Helene, Ronziere Thomas, Lassale Maria, Paya Christophe, Gauvrit Jean-Yves, Tracol Clément, Langnier-Lemercier Sophie, Samson Yves, Rosso Charlotte, Leger Anne, Deltour Sandrine, Clarencon Frederic, Shotar Eimad, Spelle Laurent, Denier Christian, Chassin Olivier, Chalumeau Vanessa, Caroff Jildaz, Venditti Laura, Turc Guillaume, Seners Pierre, Domigo Valérie, Lamy Catherine, Birchenall Julia, Isabel Clothilde, Viguier Alain, Cognard Christophe, Christine Januel Anne, Olivot Jean-Marc, Raposo Nicolas, Bonneville Fabrice, François Albucher Jean, Calviere Lionel, Touze Emmanuel, Barbier Charlotte, Schneckenburger Romain, Boulanger Marion, Cogez Julien, Guettier Sophie, Timsit Serge, Gentric Jean-Christophe, Ognard Julien, Mathias Merrien Francois, Ozkul Wermester Ozlem, Massardier Evelyne, Papagiannaki Chrysanthi, Bourdain Frédéric, Patricia Bernady, Lagoarde-Segot Laurent, Cailliez Hélène, Veunac Louis, Higue David, Wolff Valérie, Pop Raoul, Beaujeux Rémi, Mihoc Dan-Sorin, Manisor Monica, Le Bras Anthony, Evain Sarah, Le Guen Arnaud, Richter Sebastian, Hubrecht Regis, Demasles Stéphanie, Barroso Bruno, Zuber Mathieu, Farhat Wassim, Alias Quentin, Lun François, Stenvenoot Delphine, Heinzlef Olivier, Godon Hardy Sylvie, Bohotin Valentin, and Grimaud Jérôme

Subjects
medicine.medical_specialty, Standard of care, Time Factors, Neuroradiologist, 030204 cardiovascular system & hematology, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Operator (computer programming), Medicine, Humans, Registries, Thrombectomy, Advanced and Specialized Nursing, Surgeons, business.industry, Cerebral infarction, Endovascular Procedures, Cerebral Infarction, medicine.disease, Mechanical thrombectomy, Stroke, Multicenter study, Ischemic stroke, Reperfusion, Physical therapy, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

Background and Purpose: We aimed to evaluate among trained interventional neuroradiologist, whether increasing individual experience was associated with an improvement in mechanical thrombectomy (MT) procedural performance metrics. Methods: Individual MT procedural data from 5 centers of the Endovascular Treatment in Ischemic Stroke registry and 2 additional high-volume stroke centers were pooled. Operator experience was defined for each operator as a continuous variable, cumulating the number of MT procedures performed since January 2015, as MT became standard of care or, if later than this date, since the operator started performing mechanical thrombectomies in autonomy. We tested the associations between operator’s experience and procedural metrics. Results: A total of 4516 procedures were included, performed by 36 operators at 7 distinct centers, with a median of 97.5 endovascular treatment procedures per operator (interquartile range, 57–170.2) over the study period. Higher operator’s experience, analyzed as a continuous variable, was associated with a significantly shorter procedural duration (β estimate, −3.98 [95% CI, −5.1 to −2.8]; P P =0.013). Conclusions: In trained interventional neuroradiologists, increasing experience in MT is associated with significantly shorter procedural duration and better reperfusion rates, with a theoretical ceiling effect observed after around 100 procedures. These results may inform future training and practice guidelines to set minimal experience standards before autonomization, and to set-up operators’ recertification processes tailored to individual case volume and prior experience.

Published
2021

10. Prognosis and risk factors associated with asymptomatic intracranial hemorrhage after endovascular treatment of large vessel occlusion stroke: a prospective multicenter cohort study

Author

Constant Dit Beaufils, Pacôme, Labreuche, Julien, Richard, Śebastien, Fahed, Robert, Desal, Hubert Armand, Piotin, Michel P., Blanc, Raphaël, Redjem, Hocine, Escalard, Simon, Desilles, Jean Philippe, Ciccio, Gabriele, Smajda, Stanislas, Maier, Benjamin, Mazighi, Mikael, Obadia, Mikael, Sabben, Candice, Peres, Roxanne, Corabianu, Ovide, De Broucker, Thomas, Smadja, Didier, Alamowitch, Sonia, Ille, Olivier, Manchon, Eric, Garcia, Pierre Yves, Taylor, Guillaume, Ben Maacha, Malek, Wang, Adrien, Evrard, Serge, Tchikviladze, Maya, Ajili, Nadia, Lapergue, Bertrand, Weisenburger, David, Gorza, Lucas, Buard, Géraldine, Coskun, Oguzhan, Consoli, Arturo, Di Maria, Federico, Rodesh, Georges, Zimatore, Sergio, Leguen, Morgan, Gratieux, Julie D., Pico, Fernando, Rakotoharinandrasana, Haja, Tassan, Philippe, Poll, Roxanna, Marinier, Sylvie, Nighoghossian, Norbert, Riva, Roberto, Eker, Omer faruk, Turjman, Francis, Derex, Laurent, Cho, Tae-Hee, Mechtouff, Laura, Lukaszewicz, Anne Claire, Philippeau, Frédéric, Cakmak, Serkan, Blanc-Lasserre, Karine, Vallet, Anne Evelyne, Marnat, Gaultier, Gariel, Florent, Barreau, Xavier, Berge, Jerome, Veunac, Louis, Menegon, Patrice, Sibon, Igor, Lucas, Ludovic, Olindo, Stéphane, Renou, Pauline, Sagnier, Sharmila, Poli, Mathilde, Debruxelles, Sabrina, Tourdias, Thomas, Liegey, Jean Sebastien, Bourcier, Romain, Detraz, Lili, Daumas-Duport, Benjamin, Alexandre, Pierre Louis, Roy, Monica, Lenoble, Cédric, L’Allinec, Vincent, Girot, Jean Baptiste, Desal, Hubert, Guillon, Benoît, De Gaalon, Solène, Preterre, Cécile, Gory, Benjamin, Bracard, Serge R., Anxionnat, René, Braun, Marc, Derelle, Anne Laure, Tonnelet, Romain, Liao, Liang, Zhu, François, Schmitt, Emmanuelle, Planel, Sophie, Richard, Sébastien, Humbertjean, Lisa, Mione, Gioia, Lacour, Jean Christophe, Bonnerot, Mathieu, Riou-Comte, Nolwenn, Macian-Montoro, Francisco, Saleme, Suzanna, Mounayer, Charbel, Rouchaud, Aymeric M., Costalat, Vincent, Arquizan, Caroline, Dargazanli, Cyril, Gascou, Grégory, Lefèvre, Pierre Henri, Derraz, Imad, Riquelme, Carlos, Gaillard, Nicolas, Mourand, Isabelle, Corti, Lucas, Francois, Eugene, Vannier, Stéphane, Ferré, Jean-Christophe, Raoult, Hélène, Ronziere, Thomas, Lassale, Maria, Paya, Christophe, Gauvrit, Jean Yves, Tracol, Clément, Langnier-Lemercier, Sophie, Samson, Yves, Rosso, Charlotte, Leger, Anne, Deltour, Sandrine, Clarencon, Frédéric, Shotar, Eimad, Spelle, Laurent, Denier, Christian, Chalumeau, Vanessa, Caroff, Jildaz, Chassin, Olivier, Venditti, Laura, Turc, G., Naggara, Olivier N., Boulouis, Grégoire, Ben Hassen, Wagih, Seners, Pierre, Viguier, Alain, Cognard, Christophe H., Januel, Anne Christine, Olivot, Jean Marc, Raposo, Nicolas, Bonneville, Fabrice, Touze, Emmanuel, Barbier, Charlotte N., Schneckenburger, Romain, Boulanger, Marion, Cogez, Julien, Guettier, Sophie, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service Neuroradiologie diagnostique et interventionnelle [Hôpital Foch], Hôpital Foch [Suresnes], Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), P.C.D.B. and J.L. have nothing to disclose. R. Blanc, R. Bourcier, A.C., H.D., F.D.M., R.F., F.G., B. Gory, G.M., C.P., S.R., I.S. and F.Z. have nothing to disclose. M.M. reports personal fees from Amgen, personal fees from Boerhinger, personal fees from Acticor, and personal fees from Air Liquide, outside the submitted work. B.L. reports grants from Stryker, Penumbra and Microventino, outside the submitted work. S.D.G. reports personal fees and non‐financial support from Boerhinger, outside the submitted work. B. Guillon reports personal fees from Boerhinger‐Ingelheim France and Bristol‐Myers‐Squibb, outside the submitted work., Centre hospitalier universitaire de Nantes (CHU Nantes), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de neuroradiologie [Suresnes], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département de Neuro-Radiologie [Bordeaux] (DNR - Bordeaux), CHU Bordeaux [Bordeaux], Service de neurologie [CHRU Nancy], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), and The Ottawa Hospital

Subjects
Male, endovascular treatment, medicine.medical_specialty, Asymptomatic, Brain Ischemia, Cohort Studies, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Modified Rankin Scale, Internal medicine, Humans, Medicine, asymptomatic, Registries, 030212 general & internal medicine, Stroke, Thrombectomy, Intracerebral hemorrhage, business.industry, Endovascular Procedures, Odds ratio, medicine.disease, intracerebral hemorrhage, stroke, Confidence interval, 3. Good health, Treatment Outcome, Neurology, Cardiology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), prognosis, medicine.symptom, business, Intracranial Hemorrhages, 030217 neurology & neurosurgery, Cohort study
Abstract

International audience; Background and purpose: Asymptomatic intracranial hemorrhage (aICH) is a common occurrence after endovascular treatment (EVT) for acute ischemic stroke (AIS). The aims of this study were to address its impact on 3-month functional outcome and to identify risk factors for aICH after EVT. Methods: Patients with AIS attributable to anterior circulation large vessel occlusion who underwent EVT were enrolled in a multicenter prospective registry. Based on imaging performed 22–36 h post-EVT, we included patients with no intracranial hemorrhage (ICH) or aICH. Poor outcome defined as a 3-month modified Rankin Scale (mRS) score 4–6 and overall 3-month mRS score distribution were compared according to presence/absence of aICH, and aICH subtype using logistic regression. We assessed the risk factors of aICH using a multivariate logistic regression model. Results: Of the 1526 patients included in the study, 653 (42.7%) had aICH. Patients with aICH had a higher rate of poor outcome: odds ratio (OR) 1.88 (95% confidence interval [CI] 1.44–2.44). Shift analysis of mRS score found a fully adjusted OR of 1.79 (95% CI 1.47–2.18). Hemorrhagic infarction (OR 1.63 [95% CI 1.22–2.18]) and parenchymal hematoma (OR 2.99 [95% CI 1.77–5.02]) were associated with higher risk of poor outcome. Male sex, diabetes, coronary artery disease, baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score, number of passes and onset to groin puncture time were independently associated with aICH. Conclusions: Patients with aICH, irrespective of the radiological pattern, have a worse functional outcome at 3 months compared with those without ICH after EVT for AIS. The number of EVT passes and the time from onset to groin puncture are factors that could be modified to reduce deleterious ICH.

Published
2021
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11. Post-Thrombolysis Recanalization in Stroke Referrals for Thrombectomy

Author

Seners, Pierre, Turc, Guillaume, Naggara, Olivier, Hénon, Hilde, Piotin, Michel, Arquizan, Caroline, Cho, Tae-Hee, Narata, Ana-Paula, Lapergue, Bertrand, Richard, Sébastien, Legrand, Laurence, Bricout, Nicolas, Blanc, Raphaël, Dargazanli, Cyril, Gory, Benjamin, Debiais, Séverine, Tisserand, Marie, Bracard, Serge, Leclerc, Xavier, Obadia, Michael, Costalat, Vincent, Berner, Lise-Prune, Cottier, Jean-Philippe, Consoli, Arturo, Ducrocq, Xavier, Mas, Jean-Louis, Oppenheim, Catherine, Baron, Jean-Claude, Abrivard, Marie, Alamowitch, Sonia, Ben Hassen, Wagih, Berthezène, Yves, Blanc-Lasserre, Karine, Boulin, Anne, Boulouis, Grégoire, Bouly, Stephane, Bourdain, Frédéric, Calvet, David, Charron, Vladimir, Chbicheb, Mohamed, Condette-Auliac, Stéphanie, Corabianu, Ovide, Cordonnier, Charlotte, Coskun, Oguzhan, De Broucker, Thomas, Decroix, Jean-Pierre, Di Maria, Federico, Evrard, Serge, Fissellier, Mathieu, Girard, Isabelle, Lalu, Thibault, Le Coz, Patrick, Le Guen, Morgan, Ille, Olivier, Leys, Didier, Magni, Christophe, Manchon, Eric, Mazighi, Mikael, Mounier-Vehier, François, Moynier, Marinette, Muresan, Ioan-Paul, Nighoghossian, Norbert, Ong, Elodie, Ozsancak, Canan, Philippeau, Frédéric, Pico, Fernando, Rodesch, Georges, Rosolacci, Thierry, Sabben, Candice, Sablot, Denis, Tassan, Philippe, Tchikviladze, Maya, Turjman, Francis, Vallet, Anne-Evelyne, Wang, Adrien, Zins, Marc, Zuber, Mathieu, Centre Hospitalier Sainte Anne [Paris], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Cerebrovascular Unit [Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de neuroradiologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Foch [Suresnes], Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Services de neuroradiologie [Lille], Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Neuroradiologie[Montpellier], Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Université de Montpellier (UM), Hospices Civils de Lyon (HCL), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de neurologie [Lille], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)

Subjects
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, thrombectomy, incidence, magnetic resonance imaging, fibrinolysis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], stroke
Abstract

International audience; Background and Purpose—Whether all acute stroke patients with large vessel occlusion need to undergo intravenous thrombolysis before mechanical thrombectomy (MT) is debated as (1) the incidence of post-thrombolysis early recanalization (ER) is still unclear; (2) thrombolysis may be harmful in patients unlikely to recanalize; and, conversely, (3) transfer for MT may be unnecessary in patients highly likely to recanalize. Here, we determined the incidence and predictors of post-thrombolysis ER in patients referred for MT and derive ER prediction scores for trial design. Methods—Registries from 4 MT-capable centers gathering patients referred for MT and thrombolyzed either on site (mothership) or in a non MT-capable center (drip-and-ship) after magnetic resonance– or computed tomography–based imaging between 2015 and 2017. ER was identified on either first angiographic run or noninvasive imaging. In the magnetic resonance imaging subsample, thrombus length was determined on T2*-based susceptibility vessel sign. Independent predictors of no- ER were identified using multivariable logistic regression models, and scores were developed according to the magnitude of regression coefficients. Similar registries from 4 additional MT-capable centers were used as validation cohort. Results—In the derivation cohort (N=633), ER incidence was ≈20%. In patients with susceptibility vessel sign (n=498), no-ER was independently predicted by long thrombus, proximal occlusion, and mothership paradigm. A 6-point score derived from these variables showed strong discriminative power for no-ER (C statistic, 0.854) and was replicated in the validation cohort (n=353; C statistic, 0.888). A second score derived from the whole sample (including negative T2* or computed tomography–based imaging) also showed good discriminative power and was similarly validated. Highest grades on both scores predicted no-ER with >90% specificity, whereas low grades did not reliably predict ER. Conclusions—The substantial ER rate underlines the benefits derived from thrombolysis in bridging populations. Both prediction scores afforded high specificity for no-ER, but not for ER, which has implications for trial design.

Published
2018
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12. Early neurological deterioration following thrombolysis for minor stroke with isolated internal carotid artery occlusion.

Author

Boulenoir, N., Turc, G., Henon, H., Laksiri, N., Mounier‐Véhier, F., Girard Buttaz, I., Duong, D.‐L., Papassin, J., Yger, M., Triquenot, A., Lyoubi, A., Ter Schiphorst, A., Denier, C., Baron, J.‐C., Seners, P., Ben Hassen, Wagih, Lapergue, Bertrand, Lamy, Chantal, Lucas, Ludovic, and Philippeau, Frédéric

Subjects
INTERNAL carotid artery, THROMBOLYTIC therapy, STROKE, CIRCLE of Willis, PATIENTS' attitudes, TRANSIENT ischemic attack
Abstract

Background and purpose: Better understanding the incidence, predictors and mechanisms of early neurological deterioration (END) following intravenous thrombolysis (IVT) for acute stroke with mild symptoms and isolated internal carotid artery occlusion (iICAo) may inform therapeutic decisions. Methods: From a multicenter retrospective database, we extracted all patients with both National Institutes of Health Stroke Scale (NIHSS) score <6 and iICAo (i.e. not involving the Willis circle) on admission imaging, intended for IVT alone. END was defined as ≥4 NIHSS points increase within 24 h. END and no‐END patients were compared for (i) pre‐treatment clinical and imaging variables and (ii) occurrence of intracranial occlusion, carotid recanalization and parenchymal hemorrhage on follow‐up imaging. Results: Seventy‐four patients were included, amongst whom 22 (30%) patients experienced END. Amongst pre‐treatment variables, suprabulbar carotid occlusion was the only admission predictor of END following stepwise variable selection (odds ratio = 4.0, 95% confidence interval: 1.3–12.2; P = 0.015). On follow‐up imaging, there was no instance of parenchymal hemorrhage, but an intracranial occlusion was now present in 76% vs. 0% of END and no‐END patients, respectively (P < 0.001), and there was a trend toward higher carotid recanalization rate in END patients (29% vs. 9%, P = 0.07). As compared to no‐END, END was strongly associated with a poor 3‐month outcome. Conclusions: Early neurological deterioration is a frequent and highly deleterious event after IVT for minor stroke with iICAo, and is of thromboembolic origin in three out of four patients. The strong association with iICAo site—largely a function of underlying stroke etiology—may point to a different response of the thrombus to IVT. These findings suggest END may be preventable in this setting. [ABSTRACT FROM AUTHOR]

Published
2021
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13. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack

Author

Johnston, S Claiborne, Amarenco, Pierre, Albers, Gregory W, Denison, Hans, Easton, J Donald, Evans, Scott R, Held, Peter, Jonasson, Jenny, Minematsu, Kazuo, Molina, Carlos A, Wang, Yongjun, Wong, K S Lawrence, Ameriso, Sebastiá F, Donnan, Geoffrey, Lemmens, Robin, Massaro, Ayrton, Titianova, Ekaterina, Hill, Michael D, Lavados, Pablo, Skoloudik, David, Röther, Joachim, Norbert, Szegedi, Agnelli, Giancarlo, Bornstein, Natan, Tanahashi, Norio, Góngora, Angel Arauz, Pretell, Edwin, San Jose, Maria Cristina Z, Czlonkowska, Anna, Bajenaru, Ovidiu, Stakhovskaya, Ludmila, Brozman, Miroslav, Kim, Jong-Sung, Wahlgren, Nils, Michel, Patrik, Lee, Tsong Hai, Suwanwela, Nijasri Charnnarong, Kutluk, Kursad, Moskovko, Sergii, Kasner, Scott, Laskowitz, Daniel, Clark, Wayne, Nguyen, Huy Thang, Ameriso, Sebastián F, Ameriso, Sebastian, Lepera, Sandra, Romano, Marina, Paulon, David, Ioli, Pablo, Zurru, Cristina, Bruera, Guadalupe, Jure, Lorena, Klein, Francisco, Povedano, Guillermo, Levi, Christopher, Phan, Thanh, Markus, Romesh, Anderson, Craig, Sabet, Arman, Davis, Stephen, Lee, Andrew, Kleinig, Timothy, Wong, Andrew, Krause, Martin, Jannes, Jim, Wijeratne, Tissa, Hemelsoet, Dimitri, Peeters, André, Tack, Philippe, Vanacker, Peter, Laloux, Patrice, Van Landegem, William, Vanhooren, Geert, Desfontaines, Philippe, Van Orshoven, Marc, Oliveira, Fabio, Friedrich, Mauricio, Brondani, Rosane, Gagliardi, Rubens, Fabio, Soraia, Dracoulakis, Marianna, Bazan, Rodrigo, Marrone, Luiz, Pontes Neto, Octavio, Silva, Gisele, Kowacs, Pedro, Stamenova, Paraskeva, Daskalov, Marin, Staikov, Ivan, Baldaranov, Dimo, Maslarov, Dimitar, Lilovski, Hristo, Petkov, Plamen, Petrova, Neli, Mavrov, Radoslav, Markova, Veska, Petrova, Valeria, Beleva, Tanya, Kralev, Borislav, Sotirov, Nikolay, Lekova, Veska, Hristov, Dimcho, Ermenkova, Vera, Mateev, Lyudmil, Mitkova, Rumeliya, Haralanov, Liybomir, Ikonomov, Rosen, Mihailova, Margarita, Georgiev, Ivan, Shuaib, Ashfaq, Hachinski, Vladimir, Boulanger, Jean-Martin, Mann, Sharan, Hassan, Ayman, Mackey, Ariane, Menon, Bijoy, Minuk, Jeffrey, Siddiqui, Muzaffar, Eustace, Marsha, Vieira, Lucia, Selchen, Daniel, Beaudry, Michel, Stotts, Grant, Castro, Angel, Gasic, Kristo, Rivas, Rodrigo, Sanchez, Pablo, Roldan, Andres, Grossmann, Ingrid, Figueroa, Christian, Li, Jimei, Xu, Xiaolin, Chen, Huisheng, Li, Xiaohong, Yang, Yi, Zhang, Chunsheng, Wang, Baojun, Li, Guanglai, Wang, Dong, Lin, Hong, Tang, Yamei, Xu, Anding, Wang, Yanjiang, Hong, Wenke, Song, Zhi, Zhang, Xu, Jin, Xiaoping, Xu, Yun, Yan, Fuling, Zheng, Weihong, Wang, Xiaoping, Dong, Qiang, Zhao, Zhongxin, Zhang, Baorong, Zhong, Wangtao, Wen, Guoqiang, Xu, Jun, Li, Guozhong, Dong, Xueshuang, Tian, Xiangyang, Zhang, Zhaohui, Xu, En, Liu, Kaixiang, Chen, Jun, Skoda, Ondrej, Ehler, Edvard, Vaclavik, Daniel, Sanak, Daniel, Klimosova, Sylva, Vitkova, Eva, Fiksa, Jan, Mikulik, Robert, Neumann, Jiri, Plny, Richard, Leys, Didier, Sibon, Igor, Mas, Jean-Louis, Alamowitch, Sonia, Pico, Fernando, Hosseini, Hassan, Mahagne, Marie-Hélène, Touze, Emmanuel, Vadot, Wilfried, Vannier, Stéphane, Nighoghossian, Norbert, Samson, Yves, Garnier, Pierre, Ellie, Emmanuel, Guillon, Benoît, Timsit, Serge, Giroud, Maurice, Philippeau, Frédéric, Bagan-Triquenot, Aude, Wolff, Valérie, Raposo, Nicolas, Obadia, Michel, Debiais, Severine, Grimaud, Jérôme, Illouz, Stéphane, Smadja, Didier, Urbanczyk, Cédric, Berrouschot, Jörg, Weimar, Christian, Gahn, Georg, Soda, Hassan, Klimpe, Sven, Nabavi, Darius, Glahn, Jörg, Köhrmann, Martin, Krause, Lars, Terborg, Christoph, Urban, Peter, Steiner, Thorsten, Ferbert, Andreas, Dziewas, Rainer, Seidel, Günter, Thomalla, Götz, Wong, Ka Sing Lawrence, Li, Richard, Fong, Wing Chi, Cheung, Raymond, Szegedi, Norbert, Pozsegovits, Krisztián, Valikovics, Attila, Pánczél, Gyula, Rózsa, Csilla, Németh, László, Diószeghy, Péter, Óváry, Csaba, Csányi, Attila, Kerényi, Levente, Nagy, Valéria, Komoly, Sámuel, Bereczki, Dániel, Molnár, Sándor, Kondákor, István, Tanne, David, Raphaeli, Guy, Telman, Gregory, Leker, Ronen, Lampl, Yair, Corea, Francesco, Ricci, Stefano, Guidetti, Donata, Malferrari, Giovanni, Marcheselli, Simona, Micieli, Giuseppe, Zini, Andrea, Di Lazzaro, Vincenzo, Gandolfo, Carlo, Salmaggi, Andrea, Tassi, Rossana, Rasura, Maurizia, Orlandi, Giovanni, Comi, Giancarlo, Mancuso, Michelangelo, Delodovici, Marialuisa, Bovi, Paolo, Consoli, Domenico, Utsugisawa, Kimiaki, Fujita, Tsuneo, Kurihara, Hideyuki, Maruki, Chikashi, Hayashi, Takeshi, Ogiichi, Tsuneaki, Kumagai, Morio, Takenaka, Katsunobu, Toyoda, Kazunori, Takamatsu, Kazuhiro, Ogami, Ryo, Kin, Shigenari, Aoki, Takeshi, Takizawa, Katsumi, Omori, Shigehiro, Umezawa, Takehiko, Toba, Yasuyuki, Nonoyama, Yutaka, Nakagawa, Hidemitsu, Naka, Takashi, Morimoto, Masanori, Matsumoto, Shuichi, Hitotsumatsu, Tsutomu, Shingaki, Tatsuya, Okuda, Satoshi, Ota, Mamoru, Sakai, Nobuyuki, Yamada, Takeshi, Niwa, Jun, Fujita, Hitoshi, Moriki, Akihito, Yoshino, Kimihiro, Fukushima, Yoshihisa, Mori, Takahisa, Sato, Atsushi, Kusano, Yoshikazu, Kubo, Michiya, Yamazaki, Masashi, Ooasa, Takao, Nishizaki, Takafumi, Kitagawa, Naoki, Yasaka, Masahiro, Manabe, Yasuhiro, Yoshioka, Akira, Ishihara, Masayuki, Kagawa, Takato, Ichihashi, Toshikazu, Matsuoka, Hideki, Ito, Yasuhiro, Yamasaki, Masahiro, Takaba, Hitonori, Saito, Hisatoshi, Sato, Masahiro, Fukuda, Kazumasa, Endo, Sumio, Kidooka, Minoru, Umemura, Toshitaka, Kikkawa, Yuriko, Toru, Shuta, Yamada, Kentaro, Sakai, Hideki, Asari, Jun, Ezura, Masayuki, Nitta, Hisashi, Nagano, Keiko, Ochiai, Jun, Sakai, Keiichi, Kobayashi, Yasutaka, Yoshii, Yasuhiro, Miake, Hirotomo, Takita, Tomohiro, Taniguchi, Hidekazu, Kuroki, Kazuhiko, Mizota, Takamitsu, Yamamoto, Kenichi, Nakane, Hiroshi, Iwanaga, Takeshi, Chiba, Kei, Yoshimoto, Tetsuyuki, Torii, Tsuyoshi, Kitagawa, Takeo, Takashima, Hiroshi, Shirasaki, Naoki, Dehara, Makoto, Wada, Naomichi, Hamada, Kensuke, Kato, Noriyuki, Go, Yoshinori, Izumi, Ichiro, Ninomiya, Hirotomo, Kumai, Junichiro, Nakajima, Yoshikazu, Kaku, Yasuhiko, Isayama, Yukihiro, Kawanishi, Masahiro, Noda, Shinya, Yamamoto, Kazuhide, Hazama, Takanori, Takahashi, Hiroshi, Tanaka, Yohei, Hata, Takashi, Kazekawa, Kiyoshi, Furui, Eisuke, Hondo, Hideki, Sato, Nobuyuki, Kusunoki, Katsusuke, Nanri, Kazunori, Abe, Satoshi, Sasaoka, Noboru, Kuroyanagi, Takayuki, Suzuki, Hisahiko, Fukuyama, Kouzou, Nakahara, Kimihiro, Gongora, Fernando, Brito, Carlos Cantú, Careaga, Jorge Villarreal, Alfaro, Rosalia Vazquez, Leytte, Geronimo Aguayo, Berrospi, Percy, Chavez, Carlos, Rodriguez, Liliana, Custodio, Nilton, Castañeda, Cesar, Perez, Julio, Marquez, Sandra Vargas, San Jose, Maria Cristina, Baroque, Alejandro, Collantes, Ma Epifania, Aquino, Abdias, Díaz, Alejandro, Roxas, Artemio, Lokin, Johnny, Advincula, Joel, Calderon, Emerito, Navarro, Jose, Hiyadan, John, Surdilla, Arturo, Ryglewicz, Danuta, Krychowiak, Grzegorz, Fryze, Waldemar, Sobolewski, Piotr, Nowak, Ryszard, Fiszer, Urszula, Papierowska, Beata, Zieli?ska-Turek, Justyna, Lasek-Bal, Anetta, Ko?odziejska, Ewa, Kami?ska, Anna, Adamkiewicz, Bo?ena, Tutaj, Andrzej, Szkopek, Dorota, Musiatowicz, Krzysztof, B?k, Zbigniew, Brzozowski, S?awomir, Brola, Waldemar, Ferens, Antoni, Zalisz, Marek, Rejdak, Konrad, Rudzi?ska, Monika, Panea, Cristina, Simu, Mihaela, Balasa, Rodica, Cuciureanu, Iulian, Popescu, Bogdan, Sabau, Monica, Roman-Filip, Corina, Stakhovskaya, Liudmila, Pimenov, Leonid, Gekht, Alla, Milto, Anna, Shchukin, Ivan, Parfenov, Vladimir, Arkhipov, Mikhail, Vishneva, Elena, Sokolova, Nadezhda, Bogdanov, Enver, Esin, Radiy, Khasanova, Dina, Golikov, Konstantin, Melnikova, Elena, Zaslavskiy, Leonid, Voznyuk, Igor, Nazarov, Alexander, Akhmadeeva, Leila, Iakupova, Aida, Shamalov, Nikolay, Belskaya, Galina, Chuprina, Svetlana, Denisova, Olga, Drozdova, Ekaterina, Karakulova, Yuliya, Sholomov, Ilya, Spirin, Nikolay, Vostrikova, Elena, Mordvintseva, Elena, Grigoryeva, Vera, Zateyshchikov, Dmitry, Gorbachev, Vladimir, Chefranova, Zhanna, Dudarev, Mikhail, Nilk, Rostislav, 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Thang, Nguyen, Anh, Nguyen, Hung, Dean's Office (DO - AUSTIN), University of Texas at Austin [Austin], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bichat - Claude Bernard, Stanford Stroke Center, Stanford University Medical Center, AstraZeneca, Harvard T.H. Chan School of Public Health, National Cerebral and Cardiovascular Center (NCCC - OSAKA), Osaka University [Osaka], Stroke Unit (SU - BARCELONE), Vall d'Hebron University Hospital [Barcelona], Department of Neurology (Dep Neuro - BEIJING), Tiantan Hospital, Department of Medicine and Therapeutics [Hong Kong], The Chinese University of Hong Kong [Hong Kong], Murdoch University, Service de Neurologie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre d'Investigation Clinique (CIC - Brest), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Ticagrelor, Adenosine, Medizin, Aged, Aspirin, Double-Blind Method, Female, Hemorrhage, Humans, Ischemic Attack, Transient, Kaplan-Meier Estimate, Middle Aged, Platelet Aggregation Inhibitors, Purinergic P2Y Receptor Antagonists, Stroke, Medicine (all), 030204 cardiovascular system & hematology, Stringa autori originale: Johnston SC, Easton JD, 0302 clinical medicine, Myocardial infarction, Ischemic Attack, Transient, General Medicine, Clopidogrel, Denison H, 3. Good health, Minematsu K, Wang Y, SOCRATES Steering Committee and Investigators. - Free full-text sul sito dell'editore, Anesthesia, Platelet aggregation inhibitor, Evans SR, medicine.drug, Stringa autori originale: Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Jonasson J, Minematsu K, Molina CA, Wang Y, Wong KS, Ischemia, Loading dose, Molina CA, 03 medical and health sciences, medicine, business.industry, Jonasson J, medicine.disease, Albers GW, Amarenco P, Held P, Wong KS, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia.; We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.; During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.; In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).

Published
2016
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