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1. Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source:NAVIGATE ESUS MRI substudy

Author

Josep Puig, Nikolay Shamalov, Kanjana S Perera, Feryal Saad, Dániel Bereczki, Jochen B. Fiebach, Hardi Mundl, Martin J O’Donnell, Danilo Toni, Sebastián F. Ameriso, Dorte Damgaard, Roland Veltkamp, Stefan T. Engelter, Lesly A. Pearce, Byung-Woo Yoon, Keith W. Muir, Robert Mikulik, Eric E. Smith, Scott D. Berkowitz, Scott E. Kasner, Rubens José Gagliardi, Ashkan Shoamanesh, Robert G. Hart, and Mukul Sharma

Subjects
Brain Infarction, Male, medicine.medical_specialty, covert stroke, Neurological morbidity, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, Anticoagulation, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, Rivaroxaban, law, Internal medicine, cerebral microbleeds, embolic stroke, Medicine, Humans, In patient, cardiovascular diseases, Prospective Studies, rivaroxaban, Aged, Cerebral Hemorrhage, Aspirin, Embolic Stroke, business.industry, Incidence (epidemiology), ESUS, randomized clinical trial, Magnetic Resonance Imaging, Embolic stroke, Stroke, Neurology, Intracranial Embolism, Cardiology, Female, business, 030217 neurology & neurosurgery, medicine.drug, Factor Xa Inhibitors
Abstract

Background Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. Methods At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. Results Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52–1.7). Conclusions Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide. Registration: https://www.clinicaltrials.gov . Unique identifier: NCT 02313909

Published
2022

2. Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial

Author

Şerefnur Öztürk, Bodo Kirsch, Keith W. Muir, Yongjun Wang, Sebastián F. Ameriso, Antonio Arauz, Robert Mikulik, Matthias Endres, M. M. DeVries Basson, Yilong Wang, Stuart J. Connolly, Graeme J. Hankey, Wilfried Lang, Pierre Amarenco, Balakumar Swaminathan, Danilo Toni, Pablo M. Lavados, Guillaume Paré, Roland Veltkamp, Arne Lindgren, Nikolay Shamalov, Calin Pater, Martin O'Donnell, Ashkan Shoamanesh, Robert G. Hart, Antoni Dávalos, Mukul Sharma, Turgut Tatlisumak, Raf Brouns, Shinichiro Uchiyama, Luís Miguel Cunha, Dániel Bereczki, Gary Peters, Scott E. Kasner, Rubens José Gagliardi, Jens Eckstein, Anna Członkowska, Byung Woo Yoon, Scott D. Berkowitz, Hardi Mundl, Natan M. Bornstein, Jeffrey I. Weitz, George Ntaios, W. Frank Peacock, Ellison Themeles, Department of Neurosciences, Neurologian yksikkö, Clinicum, and Selçuk Üniversitesi

Subjects
Male, Infarction, Comorbidity, 030204 cardiovascular system & hematology, cerebral embolism, 3124 Neurology and psychiatry, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Risk Factors, randomized trial, Stroke, rivaroxaban, Aged, 80 and over, Rehabilitation, Age Factors, Middle Aged, 3. Good health, Treatment Outcome, Intracranial Embolism, Ischemic Attack, Transient, Cohort, cryptogenic stroke, Platelet aggregation inhibitor, Female, aspirin, Embolic Stroke of Undetermined Source (ESUS), stroke prevention, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, Article, 03 medical and health sciences, Sex Factors, Double-Blind Method, Fibrinolytic Agents, Internal medicine, medicine, Humans, Aged, Rivaroxaban, business.industry, Racial Groups, 3112 Neurosciences, medicine.disease, DEFINITION, 3121 General medicine, internal medicine and other clinical medicine, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, Fibrinolytic agent, Platelet Aggregation Inhibitors, Factor Xa Inhibitors
Abstract

WOS: 000432489900040, PubMed: 29525076, Background: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. Aims: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. Methods: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. Results: Mean age was 66.9 +/- 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. Conclusions: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research., Bayer AGBayer AG; Janssen Research and Development; Canadian Stroke Prevention Intervention Network, Grant support: Sponsored by Bayer AG and Janssen Research and Development; partial funding for the Biomarker, Genetics, Gene Expression Substudy from the Canadian Stroke Prevention Intervention Network.

Published
2018

3. 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

4. Global survey of the frequency of atrial fibrillation-associated stroke: embolic stroke of undetermined source global registry

Author

Kanjana S. Perera, Thomas Vanassche, Jackie Bosch, Balakumar Swaminathan, Hardi Mundl, Mohana Giruparajah, Miguel A. Barboza, Martin J. O’Donnell, Maia Gomez-Schneider, Graeme J. Hankey, Byung-Woo Yoon, Artemio Roxas, Philippa Lavallee, Joao Sargento-Freitas, Nikolay Shamalov, Raf Brouns, Rubens J. Gagliardi, Scott E. Kasner, Alessio Pieroni, Philipp Vermehren, Kazuo Kitagawa, Yongjun Wang, Keith Muir, Jonathan M. Coutinho, Stuart J. Connolly, Robert G. Hart, K. Czeto, M. Kahn, K.R. Mattina, S.F. Ameriso, V. Pujol-Lereis, M. Hawkes, L. Pertierra, N. Perera, A. De Smedt, R. Van Dyck, R.J. Van Hooff, L. Yperzeele, V.D.B. Gagliardi, L.G. Cerqueir, X. Yang, W. Chen, P. Amarenco, C. Guidoux, P.A. Ringleb, D. Bereczki, I. Vastagh, M. Canavan, D. Toni, A. Anzini, C. Colosimo, M. De Michele, M.T. Di Mascio, L. Durastanti, A. Falcou, S. Fausti, A. Mancini, S. Mizumo, S. Uchiyama, C.K. Kim, S. Jung, Y. Kim, J.A. Kim, J.Y. Jo, A. Arauz, A. Quiroz-Compean, J. Colin, P.J. Nederkoorn, V.P. Marianito, L. Cunha, G. Santo, F. Silva, J. Coelho, M. Kustova, K. Meshkova, G. Williams, J. Siegler, C. Zhang, N. Gallatti, M. Kruszewski, Clinical sciences, Neuroprotection & Neuromodulation, ANS - Neurovascular Disorders, and Neurology

Subjects
Male, medicine.medical_specialty, Pediatrics, global survey, 030204 cardiovascular system & hematology, frequency of atrial fibrillation, Brain Ischemia, Brain ischemia, Electrocardiography, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Internal medicine, Associated stroke, embolic stroke, Atrial Fibrillation, medicine, Humans, Registries, Survival rate, Stroke, Aged, Advanced and Specialized Nursing, Fibrillation, Medicine(all), medicine.diagnostic_test, business.industry, atrial fibrillation, cardiac rhythm monitoring, electrocardiography, embolism, stroke, Neurology (clinical), Cardiology and Cardiovascular Medicine, Incidence, Mortality rate, Age Factors, Atrial fibrillation, Middle Aged, medicine.disease, Survival Rate, Intracranial Embolism, Embolism, Ischemic Attack, Transient, Cardiology, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Background and Purpose— Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. Methods— Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. Results— Of 2144 patients with ischemic stroke, 590 (28%; 95% confidence interval, 25.6–29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%); only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years; SD, 11.5 years; 10%; 95% confidence interval, 7.6–12.6, respectively) were substantially higher than those of patients without AF (64 years; SD, 15.58 years; 4%; 95% confidence interval, 3.3–5.4; P r =0.76; P =0.0002). Conclusions— This cross-sectional global sample of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography; the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly (>75 years old) and more often women.

Published
2016

5. Role of preexisting disability in patients treated with intravenous thrombolysis for ischemic stroke

Author

László Csiba, Michał Karliński, Niaz Ahmed, Janika Kõrv, Robert Mikulik, Dalius Jatuzis, Miroslav Brozman, Viktor Švigelj, V. Demarin, Anna Członkowska, Yakup Krespi, Nils Wahlgren, Adam Kobayashi, Nikolay Shamalov, Daniel Václavík, Aleksandras Vilionskis, and Klára Fekete

Subjects
Male, medicine.medical_specialty, Endpoint Determination, medicine.medical_treatment, Comorbidity, Klinikai orvostudományok, Logistic regression, Preexisting Condition Coverage, Brain Ischemia, Disability Evaluation, Modified Rankin Scale, Internal medicine, medicine, Confidence Intervals, Odds Ratio, Humans, Disabled Persons, Thrombolytic Therapy, Registries, Stroke, Aged, Advanced and Specialized Nursing, Aged, 80 and over, business.industry, Orvostudományok, Odds ratio, Thrombolysis, Middle Aged, medicine.disease, Prognosis, Confidence interval, Logistic Models, Treatment Outcome, Physical therapy, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Abstract

Background and Purpose— Little is known about the effect of thrombolysis in patients with preexisting disability. Our aim was to evaluate the impact of different levels of prestroke disability on patients’ profile and outcome after intravenous thrombolysis. Methods— We analyzed the data of all stroke patients admitted between October 2003 and December 2011 that were contributed to the Safe Implementation of Treatments in Stroke–Eastern Europe (SITS-EAST) registry. Patients with no prestroke disability at all (modified Rankin Scale [mRS] score, 0) were used as a reference in multivariable logistic regression. Results— Of 7250 patients, 5995 (82%) had prestroke mRS 0, 791 (11%) had prestroke mRS 1, 293 (4%) had prestroke mRS 2, and 171 (2%) had prestroke mRS ≥3. Compared with patients with mRS 0, all other groups were older, had more comorbidities, and more severe neurological deficit on admission. There was no clear association between preexisting disability and the risk of symptomatic intracranial hemorrhage. Prestroke mRS 1, 2, and ≥3 were associated with increased risk of death at 3 months (odds ratio, 1.3, 2.0, and 2.6, respectively) and lower chance of achieving favorable outcome (achieving mRS 0–2 or returning to the prestroke mRS; 0.80, 0.41, 0.59, respectively). Patients with mRS ≥3 and 2 had similar vascular profile and favorable outcome (34% versus 29%), despite higher mortality (48% versus 39%). Conclusions— Prestroke disability does not seem to independently increase the risk of symptomatic intracranial hemorrhage after thrombolysis. Despite higher mortality, 1 in 3 previously disabled patients may return to his/her prestroke mRS. Therefore, they should not be routinely excluded from thrombolytic therapy.

Published
2014

6. Intravenous Thrombolysis for Stroke Recurring Within 3 Months From the Previous Event

Author

Michal, Karlinski, Adam, Kobayashi, Anna, Czlonkowska, Robert, Mikulik, Daniel, Vaclavik, Miroslav, Brozman, Zuzana, Gdovinova, Viktor, Švigelj, Laszlo, Csiba, Klara, Fekete, Janika, Kõrv, Vida, Demarin, Vanja, Bašic-Kes, Aleksandras, Vilionskis, Dalius, Jatuzis, Yakup, Krespi, Nikolay, Shamalov, Silva, Andonova, Niaz, Ahmed, and Nils, Wahlgren

Subjects
Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Hyperlipidemias, Klinikai orvostudományok, Brain Ischemia, Cohort Studies, Fibrinolytic Agents, Recurrence, medicine, Humans, Thrombolytic Therapy, Stroke, Aged, Cerebral Hemorrhage, Retrospective Studies, Advanced and Specialized Nursing, Intracerebral hemorrhage, business.industry, Patient Selection, Retrospective cohort study, Orvostudományok, Thrombolysis, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Surgery, Treatment Outcome, Tissue Plasminogen Activator, Emergency medicine, Hypertension, Administration, Intravenous, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Fibrinolytic agent, Cohort study
Abstract

Background and Purpose— According to the European license, alteplase can be given no sooner than 3 months after previous stroke. However, it is not known whether past history of stroke influences the effect of treatment. Our aim was to evaluate safety and functional outcome after intravenous thrombolysis administered in everyday practice to patients with previous stroke ≤3 months compared with those with first-ever stroke. Methods— We analyzed consecutive cases treated with alteplase between October 2003 and July 2014 contributed to the Safe Implementation of Thrombolysis for Stroke–Eastern Europe registry from 12 countries. Odds ratios were calculated using unadjusted and adjusted logistic regression. Results— Of 13 007 patients, 11 221 (86%) had no history of stroke and 249 (2%) experienced previous stroke ≤3 months before admission. Patients with previous stroke ≤3 months had a higher proportion of hypertension and hyperlipidemia. There were no significant differences in outcome, including symptomatic intracerebral hemorrhage according to European Cooperative Acute Stroke Study (unadjusted odds ratio 1.27, 95% confidence interval: 0.74–2.15), and being alive and independent at 3 months (odds ratio 0.81, 95% confidence interval: 0.61–1.09). Conclusions— Patients currently treated with alteplase, despite a history of previous stroke ≤3 months, do not seem to achieve worse outcome than those with first-ever stroke. Although careful patient selection was probably of major importance, our findings provide reassurance that this group of patients may safely benefit from thrombolysis and should not be arbitrarily excluded as a whole. Further studies are needed to identify the shortest safe time lapse from the previous event to treatment with alteplase.

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