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1. Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin

Author

Pierre Amarenco, Hans Denison, Scott R. Evans, Anders Himmelmann, Stefan James, Mikael Knutsson, Per Ladenvall, Carlos A. Molina, Yongjun Wang, S. Claiborne Johnston, Kenneth Butcher, Shuya Li, Huaguang Zheng, David Skoloudik, Lawrence Wong, Ketevana Meshkova, Nijasri C. Suwanwela, Sebastian Ameriso, Leonardo Gonzalez, Pablo Ioli, Lorena Jure, Guillermo Povedano, Guadalupe Bruera, Gustavo Herrera, Juan Jose Martin Artesi, Virginia A. Pujol Lereis, Conrado J. Estol, Maia Gomez Schneider, Santiago Pigretti, Fernando Lipovestky, María Cristina Zurru, Stephen Davis, Andrew Wong, Tissa Wijeratne, Arman Sabet, Andrew Lee, Vincent Thijs, Robin Lemmens, Laetitia Yperzeele, Geert Vanhooren, Peter Vanacker, Iris Vansteenkiste, Vicky Maqueda, André Peeters, Marie-Christine Hasenbroekx, Van Daele, Wendy Hasenbroekx, Adinda De Pauw, Regilio Oedit, Wouter De Vooght, Philippe Desfontaines, Yves Vandermeeren, Marianna D.A. Dracoulakis, Rodrigo Bazan, Octavio M. Pontes Neto, Daniel D.C. Bezerra, Luiz C. Marrone, Pedro A. Kowacs, Carla H.C. Moro, Paulo C.O. Macelino, Marco Tulio A. Pedatella, Ekaterina Titianova, Ivan Staikov, Dimitar Maslarov, Plamen Petkov, Tanya Beleva, Borislav Kralev, Nikolay Sotirov, Dimcho Hristov, Rumeliya M. Ivanova, Margarita V. Mihailova, Ashfaq M. Shuaib, Andrew Demchuk, Michel Beaudry, Anthony R. Winder, Sumiti Nayar, Xingquan Zhao, Guoqiang Wen, Xueshuang Dong, Guozhong Li, Zhaohui Zhang, Huisheng Chen, Dong Wang, Xiaohong Li, Yuncheng Wu, Xu Zhang, Baorong Zhang, Wenke Hong, Xiaogang Li, Lijuan Wang, Li Liu, Xiaolin Xu, Peifu Wang, Weihong Zheng, Jinsheng Zeng, Yukai Wang, Yan Jia, Yongqiu Li, Bo Hu, Wei Shen, Zhi Song, Zhiping Hu, Yunhai Liu, Kaifu Ke, Deqin Geng, Shigang Zhao, Runxiu Zhu, Qiumin Qu, Xiuli Zhao, Qi Wan, Yunhua Yue, Huishan Du, Meiyun Zhang, Yan Wang, Dongfang Li, Dongyu Wang, Yongqiang Li, Xufang Xie, Tingmin Yu, Qi Liu, Mingxiu Yang, Xiaoping Pan, Lijun Xu, Deen Xu, Gang Li, Anding Xu, Martin Roubec, Petr Geier, Daniel Vaclavik, Jiri Neumann, Jana Bednarova, Robert Mikulik, David Hlinovsky, Charlotte Cordonnier, Igor Sibon, Caroline Arquizan, Sonia Alamowitch, Bertrand Lapergue, Jean-Marc Olivot, Nicolas Raposo, Marie-Hélène Mahagne, Emmanuel Touze, Gilles Rodier, Stéphane Vannier, Yves Samson, Michael Obadia, Emmanuel Ellie, Benoît Guillon, Serge Timsit, Yannick Bejot, Valérie Wolff, Didier Smadja, Aude Bagan-Triquenot, Pierre Garnier, Xavier Ducrocq, Peggy Reiner, Thierry Moulin, Frédéric Philippeau, Fernando Pico, Sébastien Richard, Joachim Röther, Jörg Berrouschot, Hassan Soda, Carsten Pohlmann, Christoph Terborg, Darius G. Nabavi, Rainer Dziewas, Martin Köhrmann, Jörg Glahn, Lars Marquardt, Bernd Kallmünzer, Karin Weißenborn, Yannie Oi-Yan Soo, Richard Li, Wing Chi Fong, Siu Hung Li, Raymond Cheung, Kin Keung Yip, Joshua Wai Ming Fok, Michael Y.P. Fu, Norbert Szegedi, Krisztián Pozsegovits, Attila Valikovics, Gyula Pánczél, Csilla Rózsa, Péter Diószeghy, Attila Csányi, Levente Kerényi, Valéria Nagy, László Szapáry, Dániel Bereczki, Sándor Molnár, Gyula Timár, András G. Folyovich, Mária Sátori, Ildikó Vastagh, Praveen S. Kumar, Rajnish Kumar, Atul Prasad, Vikram Sharma, Alok Verma, Indraneel Basu, Abu Z. Ansari, Vijaya Pamidimukkala, Raghavendra B, null S, Vivek D. Junewar, Sumit Singh, Advait Prakash Kulkarni, Padma M.V. Srivastava, K. Pramod, Sanjay G. Ramteke, Jaideep Bansal, Kewal Krishan, Hrishikesh Kumar, Priyanka V. Kashyap, T.C.R. Ramakrishnan, Gopal R. Adrasetty, Amit Yeole, Rahul B. Baviskar, Giancarlo Agnelli, Danilo Toni, Stefano Ricci, Rossana Tassi, Giuseppe Micieli, Michelangelo Mancuso, Giovanni Orlandi, Alberto Chiti, Marialuisa Delodovici, Federico Carimati, Alessandro De Vito, Francesco Perini, Cinzia Finocchi, Tiziana Tassinari, Massimo Del Sette, Luisa Roveri, Andrea Zini, Guido Bigliardi, Francesca R. Pezzella, Letizia Cupini, Alessandro Adami, Giampaolo Tomelleri, Carla Zanferrari, Angel A. Arauz Góngora, Minerva López Ruíz, Angelica Ruíz Franco, José O.J. Chacon Romero, Fernando Cruz Castillo, Jose L. Ruiz-Sandoval, Jesús D. López Tapia, Edgar A. Castillo Vargas, Juan F. Gongora Rivera, Guillermo Rivera Martinez, Jorge Villarreal Careaga, Nilton Custodio, Oscar G. Pamo Reyna, Cesar A. Castañeda, Edwin J. Pretell, Nestor Najar, Julio C. Perez, Luisa Cardoza, Carlos Chavez, Maria Reyes, Anna Członkowska, Waldemar Fryze, Piotr Sobolewski, Ryszard Nowak, Dorota Szkopek, Zbigniew Bąk, Sławomir Brzozowski, Waldemar Brola, Marek Zalisz, Konrad Rejdak, Marta Bilik, Małgorzata Fudala, Andrzej Tutaj, Anetta Lasek-Bal, Jan Kochanowicz, Bartosz Karaszewski, Tomasz Berkowicz, Beata Zwiernik, Dorota Różański, Jan P. Mejnartowicz, Szymon Jurga, Jacek Rożniecki, Maciej Świat, Ovidiu A. Bajenaru, Cristina A. Panea, Mihaela A. Simu, Rodica Balasa, Dan I. Cuciureanu, Bogdan O. Popescu, Monica Sabau, Corina Roman-Filip, Liudmila Odnopozova, Oleg Artyukov, Anna Milto, Liudmila V. Stakhovskaya, Sergei Aksentiev, Svetlana E. Chuprina, Elena B. Kuznetsova, Ilya I. Sholomov, Alexander Malygin, Elena Mordvintseva, Rostislav Y. Nilk, Inna Ershova, Dina Khasanova, Leila Akhmadeeva, Aida Iakupova, Ekaterina A. Drozdova, Marine Tanashyan, Evgenij Pudov, Lybov A. Shpagina, Svetlana Berns, Liudmila G. Lenskaya, Konstantin Golikov, Andrey V. Kovalenko, Elena Vasilieva, Elena Reznik, Mikhail Zykov, Evgeniy Kovalchuk, Dmitry Popov, Andrey Belkin, Olga Androfagina, Tatyana Lokshtanova, Elena V. Melnikova, Fahmi Al-Senani, Nouf Almansour, Fawaz Alhussein, Ali Alkhathaami, Saeed Alghamdi, Miroslav Brozman, Marta Mikloskova, Georgi Krastev, Vlastimil Serdahely, Michal Kovacik, Ladislav Gurcik, Miloslav Dvorak, Egon Kurca, Andrea Cimprichova, Marian Kycina, Erika Zacharova, Richard Risnovsky, Hee-Joon Bae, Kyung Bok Lee, Yong-Jin Cho, Jong-Moo Park, Joon-Tae Kim, Jun Lee, Jae-Kwan Cha, Sung-Il Sohn, Dong-Ick Shin, Soo Joo Lee, Byung-Chul Lee, Jay Chol Choi, Moo Seok Park, Dae-Il Chang, Joung-Ho Rha, Sang Min Sung, Yangha Hwang, Jaume Roquer González, Jaime Masjuan Vallejo, Meritxell Gomis Cortina, Francisco Moniche Álvarez, Miguel Ángel Gamero García, Soledad Pérez Sánchez, Francisco Purroy García, Santiago Trillo Senín, Tomás Segura Martín, Joaquín Serena Leal, Juan Arenillas Lara, Joan Martí-Fàbregas, Aida Lago Martín, Carlos Tejero Juste, Javier Marta Moreno, Nicolás López Hernández, Lars Sjöblom, Ann Charlotte Laska, Margarita Callander, Thomas Mooe, Jan-Erik Karlsson, Mihaela Oana Romanitan, Arne Lindgren, Niaz Ahmed, Björn Cederin, Christine Kremer, Tsong-Hai Lee, Jiann-Shing Jeng, Chih-Hung Chen, Helen L. Po, Chia-Wei Liou, Huey-Juan Lin, Ruey-Tay Lin, Hsiu-Fen Lin, Li-Ming Lien, Lung Chan, Wei-Shih Huang, Wen-Yi Huang, Ta-Cheng Chen, Chin-I Chen, Po-Lin Chen, Chun-Pai Yang, Yu Sun, Aurauma Chutinet, Tasanee Tantirittisak, Sombat Muengtaweepongsa, Yongchai Nilanont, Somsak Tiamkao, Chesda Udommongkol, Witoon Jantararotai, Tabtim Chongsuvivatwong, Suwat Srisuwananukorn, Wasutha Khaykhaew, Supachai Paiboonpol, Makorn Limudomporn, Saengduan Mayotarn, Kanoksri Samintharapanya, Arkhom Arayawichanon, Thanoot Thamangraksat, Duangpol Srimanee, Galyna Chmyr, Nataliya Tomakh, Alla Cherkez, Sergii Moskovko, Vadym Nikonov, Svitlana Shkrobot, Lyudmyla Shulga, Hanna Hrebeniuk, Valentyna Yavorska, Nataliia Lytvynenko, Marta Khavunka, Iryna Kobets, Nataliia Chemer, Ivanna Tashchuk, Olha Myronova, Thang H. Nguyen, Tan V. Vo, Thanh T. Tran, Nga T.P. Nguyen, Anh D. Nguyen, Binh T. Nguyen, Thang B. Nguyen, Ngoc H. Nguyen, Quang D. Nguyen, Nhan D. Le, Dai D. Pham., UCL - SSS/IONS - Institute of NeuroScience, UCL - (MGD) Service de neurologie, Yperzeele, Laetitia, and THALES Steering Committee and Investigators

Subjects
Male, Atherosclerotic stenosis, Ticagrelor, Neurology, Neurologi, Original Contributions, population, Constriction, Pathologic, Severity of Illness Index, Recurrence, Secondary Prevention, Medicine, Cardiac and Cardiovascular Systems, Stroke, education.field_of_study, Aspirin, Kardiologi, Dual Anti-Platelet Therapy, Ischemic strokes, Middle Aged, stroke, Ischemic Attack, Transient, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Cardiology, ÍNDICE DE GRAVIDADE DA DOENÇA, Female, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, aspirin, Population, atherosclerosis, death, ticagrelor, transient ischemic attack, Clinical and Population Sciences, Internal medicine, Humans, education, Aged, Ischemic Stroke, Proportional Hazards Models, Advanced and Specialized Nursing, business.industry, Atherosclerosis, medicine.disease, Cerebrovascular Disorders, Ischemic stroke, Human medicine, Neurology (clinical), business, Platelet Aggregation Inhibitors
Abstract

Supplemental Digital Content is available in the text., Background and Purpose: Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. Methods: In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Results: Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001). Conclusions: In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171). Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429.

Published
2020

2. Safety and efficacy of GABAA α5 antagonist S44819 in patients with ischaemic stroke : A multicentre, double-blind, randomised, placebo-controlled trial

Author

Peter D. Schellinger, Agnes Koves, Usman A. Khan, Didier Smadja, Gabriel Rodriguez Freitas, Ralf Lindert, Bill O'brien, Jaime Masjuan Vallejo, Aida Lago Martin, Cesar Minelli, Hassan Hosseini, Marine Wattez, Martin Grond, Claudio L. Bassetti, Konrad Rejdak, Marie-Laure Audoli-Inthavong, Luisa Rover, Pere Cardona, Kenneth Butcher, Gabriel R. de Freitas, Gyula Panczel, Tomas Segura Martin, Marianna Gottschal, Maurício André Gheller Friedrich, Hugues Chabriat, Alvaro Ximenez Carrillo, Laura Dorado, Jean-Philippe Neau, Joerg Berrouschot, D. G. Nabavi, Carla H.C. Moro, Nina De Klippel, Norbert Szegedi, Tomasz Berkowicz, Jesse Dawson, Andras Folyovich, Christian Denier, Jean-Louis Mas, Klaus Gröschel, Amit K Mistri, Thanh G. Phan, Timothy Kleinig, Aurore Sors, Dirk M. Hermann, Louise Shaw, Christine Roffe, Nikola Sprigg, Man Seok Park, Hans-Christoph Diener, Hassan Soda, Maite Martinez Zabaleta, Pietro Bassi, Luiz Carlos Porcello Marrone, Dylan Blacquiere, László Vécsei, Stephen N. Davis, Giuseppe Lembo, Rohan Grimley, Charlotte Cordonnier, Geert Vanhooren, Bernd Kallmuenzer, Peter Dioszeghy, Mikael Mazighi, Waldemar Brola, Francisco Moniche Alvarez, Yangha Hwang, Attila Valikovics, Waldemar Fryze, Philippe Desfontaines, Jaume Roquer Gonzalez, David Cohen, Zbigniew Bak, Csaba Ovary, Jae-Kwan Cha, Gisele Sampaio Silva, Carlos A. Molina, Rodrigo Bazan, Hee-Joon Bae, Rubens José Gagliardi, Geoffrey Cloud, Anna Członkowska, Attila Csanyi, Leonardo Barbarini, Sergi Amaro, Jong Sung Kim, Daniel Bereczki, Katharina Althaus, Robin Lemmens, Anetta Lasek-Bal, Theodore Wein, Piotr Sobolewski, Diederik Willem Dippel, Danilo Toni, Laszlo Szapary, Suzanne Ragab, Andrew Wong, Ute Marx, Estelle Lambert, Igor Sibon, Wim M. Mulleners, Ondrej Skoda, and Maciej Swiat

Subjects
0301 basic medicine, medicine.medical_specialty, business.industry, medicine.medical_treatment, Placebo-controlled study, Medizin, Placebo, law.invention, Clinical trial, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Randomized controlled trial, law, Modified Rankin Scale, Internal medicine, ischemic stroke, medicine, Clinical endpoint, Neurology (clinical), Stroke recovery, business, Adverse effect, 030217 neurology & neurosurgery
Abstract

Summary Background S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke. Methods RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18–85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7–20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0–1 versus 2–6 and 0–2 versus 3–6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov , NCT02877615 . Findings Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64–1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81–1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0–2 vs 3–6 or mRS 0–1 vs 2–6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2–8] in 150 mg S44819 group, 4 [2–7] in 300 mg S44819 group, and 4 [2–6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0–26·0] in 150 mg S44819 group, 23·0 [19·0–26·5] in 300 mg S44819 group, and 22·0 [17·0–26·0] in placebo group), time needed to complete parts A (50 s [IQR 42–68] in 150 mg S44819 group, 49 s [36–63] in 300 mg S44819 group, and 50 s [38–68] in placebo group) and B (107 s [81–144] in 150 mg S44819 group, 121 s [76–159] in 300 mg S44819 group, and 130 s [86–175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60–100] in 150 mg S44819 group, 90 [70–100] in 300 mg S44819 group, and 90 [70–100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths. Interpretation There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans. Funding Servier.

Published
2020

3. Cryptogenic postpartum stroke

Author

István Gubucz, Zoltán Szakács, Zsolt May, Norbert Szegedi, and Dániel Bereczki

Subjects
Adult, HELLP Syndrome, medicine.medical_specialty, Peripartum cardiomyopathy, Brain Ischemia, Paradoxical embolism, Pregnancy, Risk Factors, Internal medicine, medicine, Humans, Medical history, Stroke, reproductive and urinary physiology, Thrombectomy, Eclampsia, Cesarean Section, Cerebral infarction, business.industry, Postpartum Period, Infarction, Middle Cerebral Artery, medicine.disease, Cerebral Angiography, Cardiology, Patent foramen ovale, Female, Stents, Surgery, Neurology (clinical), Tomography, X-Ray Computed, business, Postpartum period
Abstract

An estimated 25-40% of ischemic strokes are classified as cryptogenic, which means the cause of the cerebral infarction remains unidentified. One of the potential pathomechanisms - especially among young patients with no cardiovascular risk factors - is paradoxical embolism through a patent foramen ovale. Pregnancy, cesarean delivery and the postpartum period are associated with an increased risk of cerebrovascular events. Factors that may contribute to ischemic strokes during gestation and puerperium include classic cardiovascular risk factors, changes in hemostaseology/hemodynamics, and pregnancy-specific disorders such as pre-eclampsia, eclampsia, postpartum cerebral angiopathy or peripartum cardiomyopathy. In this case report, we present a 36-year-old thrombolysis candidate undergoing mechanical thrombectomy 3 weeks after a cesarean section due to HELLP-syndrome. After evaluation of anamnestic and diagnostic parameters, closure of the patent foramen ovale has been performed. In the absence of specific guidelines, diagnostic work-up for cryptogenic stroke should be oriented after the suspected pathomechanism based on patient history and clinical picture. As long as definite evidences emerge, management of cryptogenic stroke patients with pathogenic right-to-left shunt remains individual based on the mutual decision of the patient and the multidisciplinary medical team.

Published
2016

4. Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes)

Author

J. Donald Easton, Maria Aunes, Gregory W. Albers, Pierre Amarenco, Sara Bokelund-Singh, Hans Denison, Scott R. Evans, Peter Held, Marianne Jahreskog, Jenny Jonasson, Kazuo Minematsu, Carlos A. Molina, Yongjun Wang, K.S. Lawrence Wong, S. Claiborne Johnston, Sebastiá F. Ameriso, Geoffrey Donnan, Robin Lemmens, Ayrton Massaro, Ekaterina Titianova, Michael D. Hill, Pablo Lavados, David Skoloudik, Joachim Röther, Szegedi Norbert, Giancarlo Agnelli, Natan Bornstein, Norio Tanahashi, Angel Arauz Góngora, Edwin Pretell, Maria Cristina Z. San Jose, Anna Czlonkowska, Ovidiu Bajenaru, Ludmila Stakhovskaya, Miroslav Brozman, Jong-Sung Kim, Nils Wahlgren, Patrik Michel, Tsong Hai Lee, Nijasri Charnnarong Suwanwela, Kursad Kutluk, Sergii Moskovko, Scott Kasner, Daniel Laskowitz, Wayne Clark, Huy Thang Nguyen, Sebastian Ameriso, Sandra Lepera, Marina Romano, David Paulon, Pablo Ioli, Cristina Zurru, Guadalupe Bruera, Lorena Jure, Francisco Klein, Guillermo Povedano, Christopher Levi, Thanh Phan, Romesh Markus, Craig Anderson, Arman Sabet, Stephen Davis, Andrew Lee, Timothy Kleinig, Andrew Wong, Martin Krause, Jim Jannes, Tissa Wijeratne, Dimitri Hemelsoet, André Peeters, Philippe Tack, Peter Vanacker, Patrice Laloux, William Van Landegem, Geert Vanhooren, Philippe Desfontaines, Marc Van Orshoven, Fabio Oliveira, Mauricio Friedrich, Rosane Brondani, Rubens Gagliardi, Soraia Fabio, Marianna Dracoulakis, Rodrigo Bazan, Luiz Marrone, Octavio Pontes Neto, Gisele Silva, Pedro Kowacs, Paraskeva Stamenova, Marin Daskalov, Ivan Staikov, Dimo Baldaranov, Dimitar Maslarov, Hristo Lilovski, Plamen Petkov, Neli Petrova, Radoslav Mavrov, Veska Markova, Valeria Petrova, Tanya Beleva, Borislav Kralev, Nikolay Sotirov, Veska Lekova, Dimcho Hristov, Vera Ermenkova, Lyudmil Mateev, Rumeliya Mitkova, Liybomir Haralanov, Rosen Ikonomov, Margarita Mihailova, Ivan Georgiev, Ashfaq Shuaib, Vladimir Hachinski, Jean-Martin Boulanger, Sharan Mann, Ayman Hassan, Ariane Mackey, Bijoy Menon, Jeffrey Minuk, Muzaffar Siddiqui, Marsha Eustace, Lucia Vieira, Daniel Selchen, Michel Beaudry, Grant Stotts, Angel Castro, Kristo Gasic, Rodrigo Rivas, Pablo Sanchez, Andres Roldan, Ingrid Grossmann, Christian Figueroa, Jimei Li, Xiaolin Xu, Huisheng Chen, Xiaohong Li, Yi Yang, Chunsheng Zhang, Baojun Wang, Guanglai Li, Dong Wang, Hong Lin, Yamei Tang, Anding Xu, Yanjiang Wang, Wenke Hong, Zhi Song, Xu Zhang, Xiaoping Jin, Yun Xu, Fuling Yan, Weihong Zheng, Xiaoping Wang, Qiang Dong, Zhongxin Zhao, Baorong Zhang, Wangtao Zhong, Guoqiang Wen, Jun Xu, Guozhong Li, Xueshuang Dong, Xiangyang Tian, Zhaohui Zhang, En Xu, Kaixiang Liu, Jun Chen, Ondrej Skoda, Edvard Ehler, Daniel Vaclavik, Daniel Sanak, Sylva Klimosova, Eva Vitkova, Jan Fiksa, Robert Mikulik, Jiri Neumann, Richard Plny, Didier Leys, Igor Sibon, Jean-Louis Mas, Sonia Alamowitch, Fernando Pico, Hassan Hosseini, Marie-Hélène Mahagne, Emmanuel Touze, Wilfried Vadot, Stéphane Vannier, Norbert Nighoghossian, Yves Samson, Pierre Garnier, Emmanuel Ellie, Benoît Guillon, Serge Timsit, Maurice Giroud, Frédéric Philippeau, Aude Bagan-Triquenot, Valérie Wolff, Nicolas Raposo, Michel Obadia, Severine Debiais, Jérôme Grimaud, Stéphane Illouz, Didier Smadja, Cédric Urbanczyk, Jörg Berrouschot, Christian Weimar, Georg Gahn, Hassan Soda, Sven Klimpe, Darius Nabavi, Jörg Glahn, Martin Köhrmann, Lars Krause, Christoph Terborg, Peter Urban, Thorsten Steiner, Andreas Ferbert, Rainer Dziewas, Günter Seidel, Götz Thomalla, Richard Li, Wing Chi Fong, Raymond Cheung, Norbert Szegedi, Krisztián Pozsegovits, Attila Valikovics, Gyula Pánczél, Csilla Rózsa, László Németh, Péter Diószeghy, Csaba Óváry, Attila Csányi, Levente Kerényi, Valéria Nagy, Sámuel Komoly, Dániel Bereczki, Sándor Molnár, István Kondákor, David Tanne, Guy Raphaeli, Gregory Telman, Ronen Leker, Yair Lampl, Francesco Corea, Stefano Ricci, Donata Guidetti, Giovanni Malferrari, Simona Marcheselli, Giuseppe Micieli, Andrea Zini, Vincenzo Di Lazzaro, Carlo Gandolfo, Andrea Salmaggi, Rossana Tassi, Maurizia Rasura, Giovanni Orlandi, Giancarlo Comi, Michelangelo Mancuso, Marialuisa Delodovici, Paolo Bovi, Domenico Consoli, Kimiaki Utsugisawa, Tsuneo Fujita, Hideyuki Kurihara, Chikashi Maruki, Takeshi Hayashi, Tsuneaki Ogiichi, Morio Kumagai, Katsunobu Takenaka, Kazunori Toyoda, Kazuhiro Takamatsu, Ryo Ogami, Shigenari Kin, Takeshi Aoki, Katsumi Takizawa, Shigehiro Omori, Takehiko Umezawa, Yasuyuki Toba, Yutaka Nonoyama, Hidemitsu Nakagawa, Takashi Naka, Masanori Morimoto, Shuichi Matsumoto, Tsutomu Hitotsumatsu, Tatsuya Shingaki, Satoshi Okuda, Mamoru Ota, Nobuyuki Sakai, Takeshi Yamada, Jun Niwa, Hitoshi Fujita, Akihito Moriki, Kimihiro Yoshino, Yoshihisa Fukushima, Takahisa Mori, Atsushi Sato, Yoshikazu Kusano, Michiya Kubo, Masashi Yamazaki, Takao Ooasa, Takafumi Nishizaki, Naoki Kitagawa, Masahiro Yasaka, Yasuhiro Manabe, Akira Yoshioka, Masayuki Ishihara, Takato Kagawa, Toshikazu Ichihashi, Hideki Matsuoka, Yasuhiro Ito, Masahiro Yamasaki, Hitonori Takaba, Hisatoshi Saito, Masahiro Sato, Kazumasa Fukuda, Sumio Endo, Minoru Kidooka, Toshitaka Umemura, Yuriko Kikkawa, Shuta Toru, Kentaro Yamada, Hideki Sakai, Jun Asari, Masayuki Ezura, Hisashi Nitta, Keiko Nagano, Jun Ochiai, Keiichi Sakai, Yasutaka Kobayashi, Yasuhiro Yoshii, Hirotomo Miake, Tomohiro Takita, Hidekazu Taniguchi, Kazuhiko Kuroki, Takamitsu Mizota, Kenichi Yamamoto, Hiroshi Nakane, Takeshi Iwanaga, Kei Chiba, Tetsuyuki Yoshimoto, Tsuyoshi Torii, Takeo Kitagawa, Hiroshi Takashima, Naoki Shirasaki, Makoto Dehara, Naomichi Wada, Kensuke Hamada, Noriyuki Kato, Yoshinori Go, Ichiro Izumi, Hirotomo Ninomiya, Junichiro Kumai, Yoshikazu Nakajima, Yasuhiko Kaku, Yukihiro Isayama, Masahiro Kawanishi, Shinya Noda, Kazuhide Yamamoto, Takanori Hazama, Hiroshi Takahashi, Yohei Tanaka, Takashi Hata, Kiyoshi Kazekawa, Eisuke Furui, Hideki Hondo, Nobuyuki Sato, Katsusuke Kusunoki, Kazunori Nanri, Satoshi Abe, Noboru Sasaoka, Takayuki Kuroyanagi, Hisahiko Suzuki, Kouzou Fukuyama, Kimihiro Nakahara, Fernando Gongora, Carlos Cantú Brito, Jorge Villarreal Careaga, Rosalia Vazquez Alfaro, Geronimo Aguayo Leytte, Percy Berrospi, Carlos Chavez, Liliana Rodriguez, Nilton Custodio, Cesar Castañeda, Julio Perez, Maria Cristina San Jose, Alejandro Baroque, Epifania Collantes, Abdias Aquino, Alejandro Díaz, Artemio Roxas, Johnny Lokin, Joel Advincula, Emerito Calderon, Jose Navarro, John Hiyadan, Arturo Surdilla, Danuta Ryglewicz, Grzegorz Krychowiak, Waldemar Fryze, Piotr Sobolewski, Ryszard Nowak, Urszula Fiszer, Beata Papierowska, Justyna Zielińska-Turek, Anetta Lasek-Bal, Ewa Kołodziejska, Anna Kamińska, Bożena Adamkiewicz, Andrzej Tutaj, Dorota Szkopek, Krzysztof Musiatowicz, Zbigniew Bąk, Sławomir Brzozowski, Waldemar Brola, Antoni Ferens, Marek Zalisz, Konrad Rejdak, Monika Rudzińska, Cristina Panea, Mihaela Simu, Rodica Balasa, Iulian Cuciureanu, Bogdan Popescu, Monica Sabau, Corina Roman-Filip, Leonid Pimenov, Alla Gekht, Anna Milto, Ivan Shchukin, Vladimir Parfenov, Liudmila Stakhovskaya, Mikhail Arkhipov, Nadezhda Sokolova, Enver Bogdanov, Radiy Esin, Dina Khasanova, Konstantin Golikov, Elena Melnikova, Leonid Zaslavskiy, Igor Voznyuk, Alexander Nazarov, Leila Akhmadeeva, Aida Iakupova, Nikolay Shamalov, Galina Belskaya, Svetlana Chuprina, Olga Denisova, Ekaterina Drozdova, Yuliya Karakulova, Ilya Sholomov, Nikolay Spirin, Elena Vostrikova, Elena Mordvintseva, Vera Grigoryeva, Dmitry Zateyshchikov, Vladimir Gorbachev, Zhanna Chefranova, Mikhail Dudarev, Rostislav Nilk, Alexey Rozhdestvenskiy, Ladislav Gurcik, Miloslav Dvorak, Georgi Krastev, Egon Kurca, Juraj Vyletelka, Jong Sung Kim, Hee-Joon Bae, Yong-Won Kim, Joon-Tae Kim, Jae-Kwan Cha, Hyo Suk Nam, Dae-Il Chang, Yong-Seok Lee, Kyungmi Oh, Sung-Wook Yu, Sung-Il Sohn, Jun Lee, Han Jin Cho, Eung-Gyu Kim, Joung-Ho Rha, Seo Hyun Kim, Carlos Molina Cateriano, Joaquín Serena Leal, José Vivancos Mora, Manuel Rodríguez Yañez, Jaume Roquer González, Francisco Purroy García, Meritxell Gomis Cortina, Jaime Masjuan Vallejo, Juan Arenillas Lara, Tomás Segura Martín, José Antonio Egido Herrero, Jose Ignacio Tembl Ferrairó, Jaime Gállego Culleré, Francisco Moniche Álvarez, Anna Steinberg, Margarita Callander, Ann Charlotte Laska, Lena Bokemark, Thomas Mooe, Tor-Björn Käll, Lennart Welin, Lars Sjöblom, Joakim Hambraeus, Jörg Teichert, Hans Wannberg, Johan Sanner, Bo Ramströmer, Bo Ziedén, Stefan Olsson Hau, Claes Gustafsson, Timo Kahles, Philippe Lyrer, Marcel Arnold, Martin Liesch, Friedrich Medlin, Carlo Cereda, Georg Kägi, Andreas Luft, Emmanuel Carrera, Tsong-Hai Lee, Helen L. Po, Chang-Ming Chern, Li-Ming Lien, Lung Chan, Chung-Hsiang Liu, Shey-Lin Wu, Jiann-Der Lee, Chih-Hung Chen, Huey-Juan Lin, Ruey-Tay Lin, Wei-Hsi Chen, Yu Sun, Tasanee Tantirittisak, Sombat Muengtaweepongsa, Yongchai Nilanont, Somsak Tiamkao, Chesda Udommongkol, Kanokwan Watcharasaksilp, Witoon Jantararotai, Hadiye Sirin, Birsen Ince, Talip Asil, Murat Arsava, Tulay Kurt Incesu, Hulya Tireli, Hayriye Kucukoglu, Fikri Ak, Ali Unal, Serefnur Ozturk, Nevzat Uzuner, Galyna Chmyr, Volodymyr Lebedynets, Vadym Nikonov, Lyudmyla Shulga, Volodymyr Smolanka, Marta Khavunka, Valentyna Yavorska, Nataliya Tomakh, Olexandr Kozyolkin, Galyna Litovaltseva, Maarten Lansberg, Richard Bernstein, David Brown, Jonathan Dissin, Carmelo Graffagnino, Jonathan Harris, William Hicks, Irene Katzan, Jeffrey Kramer, Joshua Willey, Scott Silliman, Sidney Starkman, David Thaler, Margaret Tremwel, Mauricio Concha, Kumar Rajamani, Bhuvaneswari Dandapani, Brian Silver, Nathan Deal, Ira Chang, Ameer Hassan, Steven Rudolph, Kenneth Fischer, Howard Kirshner, William Logan, Sidney Mallenbaum, Hebah Hefzy, Julius Latorre, Steven Levine, Anthony Ciabarra, Rima Dafer, Benjamin Anyanwu, Laurel Cherian, Spozhmy Panezai, Anna Khanna, Jodi Dodds, Michel Torbey, James Gebel, Henry Woo, David Chiu, Xiao Androulakis, William Burgin, Maria Pineda, Engin Yilmaz, Irfan Altafullah, Christine Boutwell, Salvador Cruz-Flores, Biggya Sapkota, Pierre Fayad, Michael Jacoby, Shahid Rafiq, Efrain Salgado, Eugene Lafranchise, Warren Felton, Ramesh Madhavan, Osama Zaidat, Connie Pieper, Ralph Riviello, Aaron Burnett, Michelle Fischer, Nina Gentile, Christopher Calder, Dennis Dietrich, Jonathan Cross, Larry Blankenship, Liliana Montoya, Wendell Grogan, Mark Young, Farrukh Khan, Duane Campbell, Nizar Daboul, Andrey Espinoza, Paul Cullis, Gilberto Concepcion, John Wulff, Haider Afzal, Naseem Jaffrani, William Reiter, Tamjeed Arshad, Timothy Lukovits, James Welker, Fen Lei Chang, Aamir Badruddin, Viken Babikian, Ravi Menon, James Sander, Mellanie Springer, Ashish Nanda, Luis Mas, Raj Rajan, Bruce Silverman, David Huang, David Carpenter, Joni Clark, Marilou Ching, Sunitha Santhakumar, Jeffrey Gould, Vibhav Bansal, Gabriel Vidal, Timothy Mikesell, John Brick, William French, Qaisar Shah, Christine Holmstedt, Nadir Ishag-Osman, John Kostis, Abbas Shehadeh, Pramodkumak Sethi, Asher Imam, Carl Mccomas, Duc Tran, Mehari Gebreyohanns, Brian Wiseman, Maheen Malik, Aron Schwarcz, Dorothea Altschul, John Castaldo, Amer Alshekhlee, Stephen Gancher, Nagesh Krish, Mai Nguyen-Huynh, Margaret Tremwell, Jitendra Sharma, Lance Lee, William Neil, Fazeel Siddiqui, Ali Malek, Charles Romero, Thang Nguyen Huy, Hoa Hoang, Thang Nguyen, Anh Nguyen, Hung Nguyen, Laboratoire de Recherche Vasculaire Translationnelle ( LVTS ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), AstraZeneca, National Cerebral and Cardiovascular Center ( NCCC - OSAKA ), Osaka University [Osaka], Department of Neurology ( Dep Neuro - BEIJING ), Tiantan Hospital, University of Melbourne, Faculty of Mathematics and Statistics, Ton Duc Thang University, Ho Chi Minh City, Heidelberg University, Centre hospitalier de Namur, IBM Thomas J. Watson Research Center, IBM, Bulgarian Academy of Sciences, Department of Clinical Neurological Sciences [London, Canada], University of Western Ontario ( UWO ), Servicio de Neurologia ( SANTIAGO - Neurologie ), Universidad de Santiago de Chile [Santiago] ( USACH ) -Universidad del Desarrollo, Institut de Chimie de Clermont-Ferrand - Clermont Auvergne ( ICCF ), Sigma CLERMONT ( Sigma CLERMONT ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Universidad de Talca, Shanghai Second Polytechnic University, Northwest Normal University [Lanzhou], Zhongda Hospital, Southeast University [Jiangsu], Cryogenics Laboratory ( CRYOGENICS LABORATORY ), Huazhong University of Science and Technology [Wuhan] ( HUST ) -Wuhan University [China], Centre for Synthetic and Systems Biology, University of Edinburgh-School of Biological Sciences, Duke university [Durham], Fiber Glass, Glass Business and Discovery Center, PPG Industries, National University of Defense Technology [Changsha], School of Oceanography [Seattle], University of Washington [Seattle], Key Laboratory of New Processing Technology for Nonferrous Metals and Materials, Guilin University of Technologie, Laboratoire de Génie Electrique et Ferroélectricité ( LGEF ), Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Bordeaux ( UB ), Service de Pédiatrie, Centre Hospitalier Universitaire de Nice ( CHU Nice ) -Hôpital l'Archet, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier de Versailles ( CHV ), Service de neurologie, Hôpital Sainte-Anne, Functional Exploration of Nervous, CHU Grenoble, Service de Neurologie [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière ( NEMESIS-CRICM ), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Français de Mécanique Avancée ( IFMA ), Neurologie - Côte Basque ( NEUROLOGIE ), Hopital, Laboratoire d'Intégration des Systèmes et des Technologies ( LIST ), Université Paris-Saclay-Direction de Recherche Technologique (CEA) ( DRT (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) ( GGB ), Institut Brestois Santé Agro Matière ( IBSAM ), Université de Brest ( UBO ) -Université de Brest ( UBO ) -EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CIC Brest, Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de la Cavale Blanche, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHU Strasbourg, Imagerie cérébrale et handicaps neurologiques, Institut des sciences du cerveau de Toulouse. ( ISCT ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès ( UT2J ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès ( UT2J ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Neurology, Asklepios Klinik Altona, Department of Neurology and Stroke Center, Universität Duisburg-Essen [Essen], Department of Neurology, University of Mainz, Vivantes Klinikum Neukölln, University of Erlangen, University Hospital Münster, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), PROTOMED, Neurology Department, Ichilov Medical Center, Internal and Cardiovascular Medicine - Stroke Unit ( PERUGIA - ICM-SU ), Università degli Studi di Perugia ( UNIPG ), University Hospital San Raffaele Milan, Scientific Institute and University Ospedale San Raffaele, Dipartimento di Scienze Fisiche, della Terra e dell'Ambiente., Università degli Studi di Siena ( UNISI ), Department of Education, Yamagata University, Nippon Medical School, Catalan Institute of Ornithology (ICO), Museu de Ciències Naturals (Zoologia), Wroclaw University of Science and Technology, Department of neurology, Jagiellonian University [Krakow] ( UJ ), LInguistique et DIdactique des Langues Étrangères et Maternelles ( LIDILEM ), Université Stendhal - Grenoble 3-Université Grenoble Alpes ( UGA ), Metacohorts Consortium, GenXpro GmBH, Lausanne University Hospital, Lausanne university hospital, Northeastern University [Boston], 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), National Cerebral and Cardiovascular Center (NCCC - OSAKA), Department of Neurology (Dep Neuro - BEIJING), Bulgarian Academy of Sciences (BAS), University of Western Ontario (UWO), Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Shanghai Polytechnic University (SSPU), Cryogenics Laboratory (CRYOGENICS LABORATORY), Huazhong University of Science and Technology [Wuhan] (HUST)-Wuhan University [China], Centre for Synthetic and Systems Biology (Ssynthsys), University of Edinburgh, Duke University [Durham], National University of Defense Technology [China], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Bordeaux (UB), Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier de Versailles André Mignot (CHV), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Français de Mécanique Avancée (IFMA), Neurologie - Côte Basque (NEUROLOGIE), Centre hospitalier universitaire de Nantes (CHU Nantes), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Internal and Cardiovascular Medicine - Stroke Unit (PERUGIA - ICM-SU), Università degli Studi di Perugia (UNIPG), Università degli Studi di Siena = University of Siena (UNISI), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurologie - Côte Basque, Centre Hospitalier de la Côte Basque (CHCB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Università degli Studi di Perugia = University of Perugia (UNIPG), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-SIGMA Clermont (SIGMA Clermont), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Jagiellonian University [Krakow] (UJ), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Weimar, Christian (Beitragende*r), and Calvez, Ghislaine

Subjects
Male, Risk, Ticagrelor, Adenosine, [SDV]Life Sciences [q-bio], Population, Medizin, Hemorrhage, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Platelet aggregation inhibitors, Physiology (medical), [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Humans, Myocardial infarction, education, Stroke, ComputingMilieux_MISCELLANEOUS, Aged, Aspirin, Ischemic attack, Transient, Female, Ischemic Attack, Transient, Purinergic P2Y Receptor Antagonists, Treatment Outcome, Cardiology and Cardiovascular Medicine, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [ SDV ] Life Sciences [q-bio], Ischemic Attack, business.industry, medicine.disease, Clopidogrel, [SDV] Life Sciences [q-bio], Anesthesia, Platelet aggregation inhibitor, business, 030217 neurology & neurosurgery, TIMI, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Published
2017

5. 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, Rozhdestvenskiy, Alexey, Gurcik, Ladislav, Dvorak, Miloslav, Krastev, Georgi, Kurca, Egon, Vyletelka, Juraj, Kim, Jong Sung, Bae, Hee-Joon, Kim, Yong-Won, Kim, Joon-Tae, Cha, Jae-Kwan, Nam, Hyo Suk, Chang, Dae-Il, Lee, Yong-Seok, Oh, Kyungmi, Yu, Sung-Wook, Sohn, Sung-Il, Lee, Jun, Cho, Han Jin, Kim, Eung-Gyu, Rha, Joung-Ho, Kim, Seo Hyun, Cateriano, Carlos Molina, Leal, Joaquín Serena, Mora, José Vivancos, Yañez, Manuel Rodríguez, González, Jaume Roquer, García, Francisco Purroy, Cortina, Meritxell Gomis, Vallejo, Jaime Masjuan, Lara, Juan Arenillas, Martín, Tomás Segura, Herrero, José Antonio Egido, Ferrairó, Jose Ignacio Tembl, Culleré, Jaime Gállego, Álvarez, Francisco Moniche, Steinberg, Anna, Callander, Margarita, Laska, Ann Charlotte, Bokemark, Lena, Mooe, Thomas, Käll, Tor-Björn, Welin, Lennart, Sjöblom, Lars, Hambraeus, Joakim, Teichert, Jörg, Wannberg, Hans, Sanner, Johan, Ramströmer, Bo, Ziedén, Bo, Hau, Stefan Olsson, Gustafsson, Claes, Kahles, Timo, Lyrer, Philippe, Arnold, Marcel, Liesch, Martin, Medlin, Friedrich, Cereda, Carlo, Kägi, Georg, Luft, Andreas, Carrera, Emmanuel, Lee, Tsong-Hai, Po, Helen L, Chern, Chang-Ming, Lien, Li-Ming, Chan, Lung, Liu, Chung-Hsiang, Wu, Shey-Lin, Lee, Jiann-Der, Chen, Chih-Hung, Lin, Huey-Juan, Lin, Ruey-Tay, Chen, Wei-Hsi, Sun, Yu, Tantirittisak, Tasanee, Muengtaweepongsa, Sombat, Nilanont, Yongchai, Tiamkao, Somsak, Udommongkol, Chesda, Watcharasaksilp, Kanokwan, Jantararotai, Witoon, Sirin, Hadiye, Ince, Birsen, Asil, Talip, Arsava, Murat, Incesu, Tulay Kurt, Tireli, Hulya, Kucukoglu, Hayriye, Ak, Fikri, Unal, Ali, Ozturk, Serefnur, Uzuner, Nevzat, Chmyr, Galyna, Lebedynets, Volodymyr, Nikonov, Vadym, Shulga, Lyudmyla, Smolanka, Volodymyr, Khavunka, Marta, Yavorska, Valentyna, Tomakh, Nataliya, Kozyolkin, Olexandr, Litovaltseva, Galyna, Lansberg, Maarten, Bernstein, Richard, Brown, David, Dissin, Jonathan, Graffagnino, Carmelo, Harris, Jonathan, Hicks, William, Katzan, Irene, Kramer, Jeffrey, Willey, Joshua, Silliman, Scott, Starkman, Sidney, Thaler, David, Tremwel, Margaret, Concha, Mauricio, Rajamani, Kumar, Dandapani, Bhuvaneswari, Silver, Brian, Deal, Nathan, Chang, Ira, Hassan, Ameer, Rudolph, Steven, Fischer, Kenneth, Kirshner, Howard, Logan, William, Mallenbaum, Sidney, Hefzy, Hebah, Latorre, Julius, Levine, Steven, Ciabarra, Anthony, Dafer, Rima, Anyanwu, Benjamin, Cherian, Laurel, Panezai, Spozhmy, Khanna, Anna, Dodds, Jodi, Torbey, Michel, Gebel, James, Woo, Henry, Chiu, David, Androulakis, Xiao, Burgin, William, Pineda, Maria, Yilmaz, Engin, Altafullah, Irfan, Boutwell, Christine, Cruz-Flores, Salvador, Sapkota, Biggya, Fayad, Pierre, Jacoby, Michael, Rafiq, Shahid, Salgado, Efrain, Lafranchise, Eugene, Felton, Warren, Madhavan, Ramesh, Zaidat, Osama, Pieper, Connie, Riviello, Ralph, Burnett, Aaron, Fischer, Michelle, Gentile, Nina, Calder, Christopher, Dietrich, Dennis, Cross, Jonathan, Blankenship, Larry, Montoya, Liliana, Grogan, Wendell, Young, Mark, Khan, Farrukh, Campbell, Duane, Daboul, Nizar, Espinoza, Andrey, Cullis, Paul, Concepcion, Gilberto, Wulff, John, Afzal, Haider, Jaffrani, Naseem, Reiter, William, Arshad, Tamjeed, Lukovits, Timothy, Welker, James, Chang, Fen Lei, Badruddin, Aamir, Babikian, Viken, Menon, Ravi, Sander, James, Springer, Mellanie, Nanda, Ashish, Mas, Luis, Rajan, Raj, Silverman, Bruce, Huang, David, Carpenter, David, Clark, Joni, Ching, Marilou, Santhakumar, Sunitha, Gould, Jeffrey, Bansal, Vibhav, Vidal, Gabriel, Mikesell, Timothy, Brick, John, French, William, Shah, Qaisar, Holmstedt, Christine, Ishag-Osman, Nadir, Kostis, John, Shehadeh, Abbas, Sethi, Pramodkumak, Imam, Asher, Mccomas, Carl, Tran, Duc, Gebreyohanns, Mehari, Wiseman, Brian, Malik, Maheen, Schwarcz, Aron, Altschul, Dorothea, Castaldo, John, Alshekhlee, Amer, Gancher, Stephen, Krish, Nagesh, Nguyen-Huynh, Mai, Tremwell, Margaret, Sharma, Jitendra, Lee, Lance, Neil, William, Siddiqui, Fazeel, Malek, Ali, Romero, Charles, Huy, Thang Nguyen, Hoang, Hoa, Nguyen, 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

6. Transient deficits after inadvertent intrathecal trigger-point injection with lidocaine

Author

Nora Peto, Dániel Bereczki, and Norbert Szegedi

Subjects
Adult, Lidocaine, Pneumorrhachis, Nystagmus, Ventricular system, Intrathecal, Dysarthria, Vertigo, medicine, Humans, Anesthetics, Local, Injections, Spinal, Anisocoria, Neck Pain, biology, business.industry, biology.organism_classification, Paresis, Hemiparesis, Anesthesia, Pneumocephalus, Female, Neurology (clinical), medicine.symptom, business, medicine.drug
Abstract

A 43-year-old woman had trigger-point injections for chronic neck pain by a traditional Chinese medicine physician. Paravertebral muscles at C5-C6 were infiltrated with lidocaine. Thirty minutes later, right-sided hemiparesis with nystagmus, dysarthria, and anisocoria developed. The patient complained of vertigo, vomited multiple times, and became somnolent. Neuroimaging revealed air in the ventricular system (figure 1) and in the dural sheath of the fifth cervical nerve root (figure 2), implying an accidental intrathecal injection and thus a possible direct effect of lidocaine. Three hours later, neurologic symptoms resolved gradually and the patient recovered fully. MRI revealed no intraparenchymal damage.

Published
2016

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