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1. Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation: The GLORIA-AF registry

Author

George Ntaios, Menno V. Huisman, Hans-Christoph Diener, Jonathan L. Halperin, Christine Teutsch, Sabrina Marler, Venkatesh K. Gurusamy, Milla Thompson, Gregory Y.H. Lip, Brian Olshansky, Dzifa Wosornu Abban, Nasser Abdul, Atilio Marcelo Abud, Fran Adams, Srinivas Addala, Pedro Adragão, Walter Ageno, Rajesh Aggarwal, Sergio Agosti, Piergiuseppe Agostoni, Francisco Aguilar, Julio Aguilar Linares, Luis Aguinaga, Jameel Ahmed, Allessandro Aiello, Paul Ainsworth, Jorge Roberto Aiub, Raed Al-Dallow, Lisa Alderson, Jorge Antonio Aldrete Velasco, Dimitrios Alexopoulos, Fernando Alfonso Manterola, Pareed Aliyar, David Alonso, Fernando Augusto Alves da Costa, José Amado, Walid Amara, Mathieu Amelot, Nima Amjadi, Fabrizio Ammirati, Marianna Andrade, Nabil Andrawis, Giorgio Annoni, Gerardo Ansalone, M.Kevin Ariani, Juan Carlos Arias, Sébastien Armero, Chander Arora, Muhammad Shakil Aslam, M. Asselman, Philippe Audouin, Charles Augenbraun, S. Aydin, Ivaneta Ayryanova, Emad Aziz, Luciano Marcelo Backes, E. Badings, Ermentina Bagni, Seth H. Baker, Richard Bala, Antonio Baldi, Shigenobu Bando, Subhash Banerjee, Alan Bank, Gonzalo Barón Esquivias, Craig Barr, Maria Bartlett, Vanja Basic Kes, Giovanni Baula, Steffen Behrens, Alan Bell, Raffaella Benedetti, Juan Benezet Mazuecos, Bouziane Benhalima, Jutta Bergler-Klein, Jean-Baptiste Berneau, Richard A. Bernstein, Percy Berrospi, Sergio Berti, Andrea Berz, Elizabeth Best, Paulo Bettencourt, Robert Betzu, Ravi Bhagwat, Luna Bhatta, Francesco Biscione, Giovanni BISIGNANI, Toby Black, Michael J. Bloch, Stephen Bloom, Edwin Blumberg, Mario Bo, Ellen Bøhmer, Andreas Bollmann, Maria Grazia Bongiorni, Giuseppe Boriani, D.J. Boswijk, Jochen Bott, Edo Bottacchi, Marica Bracic Kalan, Drew Bradman, Donald Brautigam, Nicolas Breton, P.J.A.M. Brouwers, Kevin Browne, Jordi Bruguera Cortada, A. Bruni, Claude Brunschwig, Hervé Buathier, Aurélie Buhl, John Bullinga, Jose Walter Cabrera, Alberto Caccavo, Shanglang Cai, Sarah Caine, Leonardo Calò, Valeria Calvi, Mauricio Camarillo Sánchez, Rui Candeias, Vincenzo Capuano, Alessandro Capucci, Ronald Caputo, Tatiana Cárdenas Rizo, Francisco Cardona, Francisco Carlos da Costa Darrieux, Yan Carlos Duarte Vera, Antonio Carolei, Susana Carreño, Paula Carvalho, Susanna Cary, Gavino Casu, Claudio Cavallini, Guillaume Cayla, Aldo Celentano, Tae-Joon Cha, Kwang Soo Cha, Jei Keon Chae, Kathrine Chalamidas, Krishnan Challappa, Sunil Prakash Chand, Harinath Chandrashekar, Ludovic Chartier, Kausik Chatterjee, Carlos Antero Chavez Ayala, Aamir Cheema, Amjad Cheema, Lin Chen, Shih-Ann Chen, Jyh Hong Chen, Fu-Tien Chiang, Francesco Chiarella, Lin Chih-Chan, Yong Keun Cho, Jong-Il Choi, Dong Ju Choi, Guy Chouinard, Danny Hoi-Fan Chow, Dimitrios Chrysos, Galina Chumakova, Eduardo Julián José Roberto Chuquiure Valenzuela, Nicoleta Cindea Nica, David J. Cislowski, Anthony Clay, Piers Clifford, Andrew Cohen, Michael Cohen, Serge Cohen, Furio Colivicchi, Ronan Collins, Paolo Colonna, Steve Compton, Derek Connolly, Alberto Conti, Gabriel Contreras Buenostro, Gregg Coodley, Martin Cooper, Julian Coronel, Giovanni Corso, Juan Cosín Sales, Yves Cottin, John Covalesky, Aurel Cracan, Filippo Crea, Peter Crean, James Crenshaw, Tina Cullen, Harald Darius, Patrick Dary, Olivier Dascotte, Ira Dauber, Vicente Davalos, Ruth Davies, Gershan Davis, Jean-Marc Davy, Mark Dayer, Marzia De Biasio, Silvana De Bonis, Raffaele De Caterina, Teresiano De Franceschi, J.R. de Groot, José De Horta, Axel De La Briolle, Gilberto de la Pena Topete, Angelo Amato Vicenzo de Paola, Weimar de Souza, A. de Veer, Luc De Wolf, Eric Decoulx, Sasalu Deepak, Pascal Defaye, Freddy Del-Carpio Munoz, Diana Delic Brkljacic, N. Joseph Deumite, Silvia Di Legge, Igor Diemberger, Denise Dietz, Pedro Dionísio, Qiang Dong, Fabio Rossi dos Santos, Elena Dotcheva, Rami Doukky, Anthony D'Souza, Simon Dubrey, Xavier Ducrocq, Dmitry Dupljakov, Mauricio Duque, Dipankar Dutta, Nathalie Duvilla, A. Duygun, Rainer Dziewas, Charles B. Eaton, William Eaves, L.A. Ebels-Tuinbeek, Clifford Ehrlich, Sabine Eichinger-Hasenauer, Steven J. Eisenberg, Adnan El Jabali, Mahfouz El Shahawy, Mauro Esteves Hernandes, Ana Etxeberria Izal, Rudolph Evonich, III, Oksana Evseeva, Andrey Ezhov, Raed Fahmy, Quan Fang, Ramin Farsad, Laurent Fauchier, Stefano Favale, Maxime Fayard, Jose Luis Fedele, Francesco Fedele, Olga Fedorishina, Steven R. Fera, Luis Gustavo Gomes Ferreira, Jorge Ferreira, Claudio Ferri, Anna Ferrier, Hugo Ferro, Alexandra Finsen, Brian First, Stuart Fischer, Catarina Fonseca, Luísa Fonseca Almeida, Steven Forman, Brad Frandsen, William French, Keith Friedman, Athena Friese, Ana Gabriela Fruntelata, Shigeru Fujii, Stefano Fumagalli, Marta Fundamenski, Yutaka Furukawa, Matthias Gabelmann, Nashwa Gabra, Niels Gadsbøll, Michel Galinier, Anders Gammelgaard, Priya Ganeshkumar, Christopher Gans, Antonio Garcia Quintana, Olivier Gartenlaub, Achille Gaspardone, Conrad Genz, Frédéric Georger, Jean-Louis Georges, Steven Georgeson, Evaldas Giedrimas, Mariusz Gierba, Ignacio Gil Ortega, Eve Gillespie, Alberto Giniger, Michael C. Giudici, Alexandros Gkotsis, Taya V. Glotzer, Joachim Gmehling, Jacek Gniot, Peter Goethals, Seth Goldbarg, Ronald Goldberg, Britta Goldmann, Sergey Golitsyn, Silvia Gómez, Juan Gomez Mesa, Vicente Bertomeu Gonzalez, Jesus Antonio Gonzalez Hermosillo, Víctor Manuel González López, Hervé Gorka, Charles Gornick, Diana Gorog, Venkat Gottipaty, Pascal Goube, Ioannis Goudevenos, Brett Graham, G. Stephen Greer, Uwe Gremmler, Paul G. Grena, Martin Grond, Edoardo Gronda, Gerian Grönefeld, Xiang Gu, Ivett Guadalupe Torres Torres, Gabriele Guardigli, Carolina Guevara, Alexandre Guignier, Michele Gulizia, Michael Gumbley, Albrecht Günther, Andrew Ha, Georgios Hahalis, Joseph Hakas, Christian Hall, Bing Han, Seongwook Han, Joe Hargrove, David Hargroves, Kenneth B. Harris, Tetsuya Haruna, Emil Hayek, Jeff Healey, Steven Hearne, Michael Heffernan, Geir Heggelund, J.A. Heijmeriks, Maarten Hemels, I. Hendriks, Sam Henein, Sung-Ho Her, Paul Hermany, Jorge Eduardo Hernández Del Río, Yorihiko Higashino, Michael Hill, Tetsuo Hisadome, Eiji Hishida, Etienne Hoffer, Matthew Hoghton, Kui Hong, Suk keun Hong, Stevie Horbach, Masataka Horiuchi, Yinglong Hou, Jeff Hsing, Chi-Hung Huang, David Huckins, kathy Hughes, A. Huizinga, E.L. Hulsman, Kuo-Chun Hung, Gyo-Seung Hwang, Margaret Ikpoh, Davide Imberti, Hüseyin Ince, Ciro Indolfi, Shujiro Inoue, Didier Irles, Harukazu Iseki, C. Noah Israel, Bruce Iteld, Venkat Iyer, Ewart Jackson-Voyzey, Naseem Jaffrani, Frank Jäger, Martin James, Sung-Won Jang, Nicolas Jaramillo, Nabil Jarmukli, Robert J. Jeanfreau, Ronald D. Jenkins, Carlos Jerjes Sánchez, Javier Jimenez, Robert Jobe, Tomas Joen-Jakobsen, Nicholas Jones, Jose Carlos Moura Jorge, Bernard Jouve, Byung Chun Jung, Kyung Tae Jung, Werner Jung, Mikhail Kachkovskiy, Krystallenia Kafkala, Larisa Kalinina, Bernd Kallmünzer, Farzan Kamali, Takehiro Kamo, Priit Kampus, Hisham Kashou, Andreas Kastrup, Apostolos Katsivas, Elizabeth Kaufman, Kazuya Kawai, Kenji Kawajiri, John F. Kazmierski, P. Keeling, José Francisco Kerr Saraiva, Galina Ketova, AJIT Singh Khaira, Aleksey Khripun, Doo-Il Kim, Young Hoon Kim, Nam Ho Kim, Dae Kyeong Kim, Jeong Su Kim, June Soo Kim, Ki Seok Kim, Jin bae Kim, Elena Kinova, Alexander Klein, James J. Kmetzo, G. Larsen Kneller, Aleksandar Knezevic, Su Mei Angela Koh, Shunichi Koide, Anastasios Kollias, J.A. Kooistra, Jay Koons, Martin Koschutnik, William J. Kostis, Dragan Kovacic, Jacek Kowalczyk, Natalya Koziolova, Peter Kraft, Johannes A. Kragten, Mori Krantz, Lars Krause, B.J. Krenning, F. Krikke, Z. Kromhout, Waldemar Krysiak, Priya Kumar, Thomas Kümler, Malte Kuniss, Jen-Yuan Kuo, Achim Küppers, Karla Kurrelmeyer, Choong Hwan Kwak, Bénédicte Laboulle, Arthur Labovitz, Wen Ter Lai, Andy Lam, Yat Yin Lam, Fernando Lanas Zanetti, Charles Landau, Giancarlo Landini, Estêvão Lanna Figueiredo, Torben Larsen, Karine Lavandier, Jessica LeBlanc, Moon Hyoung Lee, Chang-Hoon Lee, John Lehman, Ana Leitão, Nicolas Lellouche, Malgorzata Lelonek, Radoslaw Lenarczyk, T. Lenderink, Salvador León González, Peter Leong-Sit, Matthias Leschke, Nicolas Ley, Zhanquan Li, Xiaodong Li, Weihua Li, Xiaoming Li, Christhoh Lichy, Ira Lieber, Ramon Horacio Limon Rodriguez, Hailong Lin, Feng Liu, Hengliang Liu, Guillermo Llamas Esperon, Nassip Llerena Navarro, Eric Lo, Sergiy Lokshyn, Amador López, José Luís López-Sendón, Adalberto Menezes Lorga Filho, Richard S. Lorraine, Carlos Alberto Luengas, Robert Luke, Ming Luo, Steven Lupovitch, Philippe Lyrer, Changsheng Ma, Genshan Ma, Irene Madariaga, Koji Maeno, Dominique Magnin, Gustavo Maid, Sumeet K. Mainigi, Konstantinos Makaritsis, Rohit Malhotra, Rickey Manning, Athanasios Manolis, Helard Andres Manrique Hurtado, Ioannis Mantas, Fernando Manzur Jattin, Vicky Maqueda, Niccolo Marchionni, Francisco Marin Ortuno, Antonio Martín Santana, Jorge Martinez, Petra Maskova, Norberto Matadamas Hernandez, Katsuhiro Matsuda, Tillmann Maurer, Ciro Mauro, Erik May, Nolan Mayer, John McClure, Terry McCormack, William McGarity, Hugh McIntyre, Brent McLaurin, Feliz Alvaro Medina Palomino, Francesco Melandri, Hiroshi Meno, Dhananjai Menzies, Marco Mercader, Christian Meyer, Beat j. Meyer, Jacek Miarka, Frank Mibach, Dominik Michalski, Patrik Michel, Rami Mihail Chreih, Ghiath Mikdadi, Milan Mikus, Davor Milicic, Constantin Militaru, Sedi Minaie, Bogdan Minescu, Iveta Mintale, Tristan Mirault, Michael J. Mirro, Dinesh Mistry, Nicoleta Violeta Miu, Naomasa Miyamoto, Tiziano Moccetti, Akber Mohammed, Azlisham Mohd Nor, Michael Mollerus, Giulio Molon, Sergio Mondillo, Patrícia Moniz, Lluis Mont, Vicente Montagud, Oscar Montaña, Cristina Monti, Luciano Moretti, Kiyoo Mori, Andrew Moriarty, Jacek Morka, Luigi Moschini, Nikitas Moschos, Andreas Mügge, Thomas J. Mulhearn, Carmen Muresan, Michela Muriago, Wlodzimierz Musial, Carl W. Musser, Francesco Musumeci, Thuraia Nageh, Hidemitsu Nakagawa, Yuichiro Nakamura, Toru Nakayama, Gi-Byoung Nam, Michele Nanna, Indira Natarajan, Hemal M. Nayak, Stefan Naydenov, Jurica Nazli, Alexandru Cristian Nechita, Libor Nechvatal, Sandra Adela Negron, James Neiman, Fernando Carvalho Neuenschwander, David Neves, Anna Neykova, Ricardo Nicolás Miguel, George Nijmeh, Alexey Nizov, Rodrigo Noronha Campos, Janko Nossan, Tatiana Novikova, Ewa Nowalany-Kozielska, Emmanuel Nsah, Juan Carlos Nunez Fragoso, Svetlana Nurgalieva, Dieter Nuyens, Ole Nyvad, Manuel Odin de Los Rios Ibarra, Philip O'Donnell, Martin O'Donnell, Seil Oh, Yong Seog Oh, Dongjin Oh, Gilles O'Hara, Kostas Oikonomou, Claudia Olivares, Richard Oliver, Rafael Olvera Ruiz, Christoforos Olympios, Anna omaszuk-Kazberuk, Joaquín Osca Asensi, eena Padayattil jose, Francisco Gerardo Padilla Padilla, Victoria Padilla Rios, Giuseppe Pajes, A. Shekhar Pandey, Gaetano Paparella, F. Paris, Hyung Wook Park, Jong Sung Park, Fragkiskos Parthenakis, Enrico Passamonti, Rajesh J. Patel, Jaydutt Patel, Mehool Patel, Janice Patrick, Ricardo Pavón Jimenez, Analía Paz, Vittorio Pengo, William Pentz, Beatriz Pérez, Alma Minerva Pérez Ríos, Alejandro Pérez-Cabezas, Richard Perlman, Viktor Persic, Francesco Perticone, Terri K. Peters, Sanjiv Petkar, Luis Felipe Pezo, Christian Pflücke, David N. Pham, Roland T. Phillips, Stephen Phlaum, Denis Pieters, Julien Pineau, Arnold Pinter, Fausto Pinto, R. Pisters, Nediljko Pivac, Darko Pocanic, Cristian Podoleanu, Alessandro Politano, Zdravka Poljakovic, Stewart Pollock, Jose Polo Garcéa, Holger Poppert, Maurizio Porcu, Antonio Pose Reino, Neeraj Prasad, Dalton Bertolim Précoma, Alessandro Prelle, John Prodafikas, Konstantin Protasov, Maurice Pye, Zhaohui Qiu, Jean-Michel Quedillac, Dimitar Raev, Carlos Antonio Raffo Grado, Sidiqullah Rahimi, Arturo Raisaro, Bhola Rama, Ricardo Ramos, Maria Ranieri, Nuno Raposo, Eric Rashba, Ursula Rauch-Kroehnert, Ramakota Reddy, Giulia Renda, Shabbir Reza, Luigi Ria, Dimitrios Richter, Hans Rickli, Werner Rieker, Tomas Ripolil Vera, Luiz Eduardo Ritt, Douglas Roberts, Ignacio Rodriguez Briones, Aldo Edwin Rodriguez Escudero, Carlos Rodríguez Pascual, Mark Roman, Francesco Romeo, E. Ronner, Jean-Francois Roux, Nadezda Rozkova, Miroslav Rubacek, Frank Rubalcava, Andrea M. Russo, Matthieu Pierre Rutgers, Karin Rybak, Samir Said, Tamotsu Sakamoto, Abraham Salacata, Adrien Salem, Rafael Salguero Bodes, Marco A. Saltzman, Alessandro Salvioni, Gregorio Sanchez Vallejo, Marcelo Sanmartín Fernández, Wladmir Faustino Saporito, Kesari Sarikonda, Taishi Sasaoka, Hamdi Sati, Irina Savelieva, Pierre-Jean Scala, Peter Schellinger, Carlos Scherr, Lisa Schmitz, Karl-Heinz Schmitz, Bettina Schmitz, Teresa Schnabel, Steffen Schnupp, Peter Schoeniger, Norbert Schön, Peter Schwimmbeck, Clare Seamark, Greg Searles, Karl-Heinz Seidl, Barry Seidman, Jaroslaw Sek, Lakshmanan Sekaran, Carlo SERRATI, Neerav Shah, Vinay Shah, Anil Shah, Shujahat Shah, Vijay Kumar Sharma, Louise Shaw, Khalid H. Sheikh, Naruhito Shimizu, Hideki Shimomura, Dong-Gu Shin, Eun-Seok Shin, Junya Shite, Gerolamo Sibilio, Frank Silver, Iveta Sime, Tim A. Simmers, Narendra Singh, Peter Siostrzonek, Didier Smadja, David W. Smith, Marcelo Snitman, Dario Sobral Filho, Hassan Soda, Carl Sofley, Adam Sokal, Yannie Soo Oi Yan, Rodolfo Sotolongo, Olga Ferreira de Souza, Jon Arne Sparby, Jindrich Spinar, David Sprigings, Alex C. Spyropoulos, Dimitrios Stakos, Clemens Steinwender, George Stergiou, Ian Stiell, Marcus Stoddard, Anastas Stoikov, Witold Streb, Ioannis Styliadis, Guohai Su, Xi Su, Wanda Sudnik, Kai Sukles, Xiaofei Sun, H. Swart, Janko Szavits-Nossan, Jens Taggeselle, Yuichiro Takagi, Amrit Pal Singh Takhar, Angelika Tamm, Katsumi Tanaka, Tanyanan Tanawuttiwat, Sherman Tang, Aylmer Tang, Giovanni Tarsi, Tiziana Tassinari, Ashis Tayal, Muzahir Tayebjee, J.M. ten Berg, Dan Tesloianu, Salem H.K. The, Dierk Thomas, Serge Timsit, Tetsuya Tobaru, Andrzej R. Tomasik, Mikhail Torosoff, Emmanuel Touze, Elina Trendafilova, W. Kevin Tsai, Hung Fat Tse, Hiroshi Tsutsui, Tian Ming Tu, Ype Tuininga, Minang Turakhia, Samir Turk, Wayne Tcurner, Arnljot Tveit, Richard Tytus, C. Valadão, P.F.M.M. van Bergen, Philippe van de Borne, B.J. van den Berg, C. van der Zwaan, M. Van Eck, Peter Vanacker, Dimo Vasilev, Vasileios Vasilikos, Maxim Vasilyev, Srikar Veerareddy, Mario Vega Miño, Asok Venkataraman, Paolo Verdecchia, Francesco Versaci, Ernst Günter Vester, Hubert Vial, Jason Victory, Alejandro Villamil, Marc Vincent, Anthony Vlastaris, Jürgen vom Dahl, Kishor Vora, Robert B. Vranian, Paul Wakefield, Ningfu Wang, Mingsheng Wang, Xinhua Wang, Feng Wang, Tian Wang, Alberta L. Warner, Kouki Watanabe, Jeanne Wei, Christian Weimar, Stanislav Weiner, Renate Weinrich, Ming-Shien Wen, Marcus Wiemer, Preben Wiggers, Andreas Wilke, David Williams, Marcus L. Williams, Bernhard Witzenbichler, Brian Wong, Ka Sing Lawrence Wong, Beata Wozakowska-Kaplon, Shulin Wu, Richard C. Wu, Silke Wunderlich, Nell Wyatt, John (Jack) Wylie, Yong Xu, Xiangdong Xu, Hiroki Yamanoue, Takeshi Yamashita, Ping Yen Bryan Yan, Tianlun Yang, Jing Yao, Kuo-Ho Yeh, Wei Hsian Yin, Yoto Yotov, Ralf Zahn, Stuart Zarich, Sergei Zenin, Elisabeth Louise Zeuthen, Huanyi Zhang, Donghui Zhang, Xingwei Zhang, Ping Zhang, Jun Zhang, Shui Ping Zhao, Yujie Zhao, Zhichen Zhao, Yang Zheng, Jing Zhou, Sergio Zimmermann, Andrea Zini, Steven Zizzo, Wenxia Zong, and L Steven Zukerman

Subjects
SAMe-TT2R2, atrial fibrillation, non-vitamin-K antagonist oral anticoagulants, vitamin-K-antagonist oral anticoagulants, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.

Published
2021
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2. Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Author

Rustam Al-Shahi Salman, David P Minks, Dipayan Mitra, Mark A Rodrigues, Priya Bhatnagar, Johann C du Plessis, Yogish Joshi, Martin S Dennis, Gordon D Murray, David E Newby, Peter A G Sandercock, Nikola Sprigg, Jacqueline Stephen, Cathie L M Sudlow, David J Werring, William N Whiteley, Joanna M Wardlaw, Philip M White, Colin Baigent, Daniel Lasserson, Frank Sullivan, Johanna Carrie, Javier Rojas, Shannon Amoils, John Bamford, Jane Armitage, Gabriel Rinkel, Gordon Lowe, Jonathan Emberson, Karen Innes, Lynn Dinsmore, Jonathan Drever, Carol Williams, David Perry, Connor McGill, David Buchanan, Allan Walker, Aidan Hutchison, Christopher Matthews, Ruth Fraser, Aileen McGrath, Ann Deary, Rosemary Anderson, Pauli Walker, Christian Hansen, Richard Parker, Aryelly Rodriguez, Malcolm Macleod, Thomas Gattringer, Jeb Palmer, Eleni Sakka, Jennifer Adil-Smith, David Minks, Johannes du Plessis, Christine Lerpiniere, Richard O'Brien, Seona Burgess, Gillian Mead, Ruth Paulton, Fergus Doubal, Katrina McCormick, Neil Hunter, Pat Taylor, Ruwan Parakramawansha, Jack Perry, Gordon Blair, Allan MacRaild, Adrian Parry-Jones, Mary Johnes, Stephanie Lee, Kelly Marie Shaw, Ilse Burger, Martin Punter, Andrea Ingham, Jane Perez, Zin Naing, Jordi Morell, Tracy Marsden, Andrea Hall, Sally Marshall, Louise Harrison, Rowilson Jarapa, Edith Wood, Victoria O'Loughlin, David Cohen, Silvie Davies, Kelechi Njoku, Mushiya Mpelembue, Laura Burgess, Radim Licenik, Mmua Ngwako, Nabeela Nisar, Rangah Niranchanan, Tatjana Roganova, Rajaram Bathula, Joseph Devine, Anette David, Anne Oshodi, Fenglin Guo, Emmanuelle Owoyele, Varthi Sukdeo, Robert Ballantine, Mudhar Abbdul-saheb, Angela Chamberlain, Aberami Chandrakumar, Philip Poku, Kirsty Harkness, Catrin Blank, Emma Richards, Ali Ali, Faith Kibutu, Olesia Balitska, Kathryn Birchall, Pauline Bayliss, Clare Doyle, Kathy Stocks, Arshad Majis, Jo Howe, Christine Kamara, Luke Barron, Ahmad Maatouk, Ralf Lindert, Katy Dakin, Jessica Redgrave, Biju Bhaskaran, Isam Salih, Debs Kelly, Susan Szabo, Dawn Tomlin, Helen Bearne, Jean Buxton, Pauline Fitzell, Georgina Ayres, Afaq Saulat, Kathleen Horan, Joanne Garfield-Smith, Harbens Bhakri, Paul Guyler, Devesh Sinha, Thayalini Loganathan, Amber Siddiqui, Anwer Siddiqui, Lucy Coward, Swapna Kunhunny, Sharon Tysoe, Rajalakshmi Orath Prabakaran, Shyam Kelavkar, Sindhu Rashmi, David Ngo, Kheng Xiong Ng, Nisha Menon, Sweni Shah, Mark Barber, Derek Esson, Fiona Brodie, Talat Anjum, Mushtaq Wani, Manju Krishnan, Leanne Quinn, Jayne Spencer, Terry Jones, Helen Thompson-Jones, Lynne Dacey, Srikanth Chenna, Sharon Storton, Sarah Thomas, Teresa Beaty, Shelley Treadwell, Caroline Davies, Susan Tucker, Lynda Connor, Peter Slade, Glyn Gainard, Girish Muddegowda, Ranjan Sanyal, Alda Remegoso, Nenette Abano, Chelsea Causley, Racquel Carpio, Stephanie Stevens, Adrian Butler, Resti Varquez, Hayley Denic, Francis Alipio, Andrew Moores, Adrian Barry, Holly Maguire, Jeanette Grocott, Kay Finney, Sue Lyjko, Christine Roffe, Joanne Hiden, Phillip Ferdinand, Vera Cvoro, Khalil Ullah, Nicola Chapman, Mandy Couser, Susan Pound, Sean Mcauley, Senthil Raghunathan, Faye Shelton, Amanda Hedstrom, Margi Godfrey, Diane Havard, Amanda Buck, Kailash Krishnan, Nicola Gilzeane, Jack Roffe, Judith Clarke, Katherine Whittamore, Saima Sheikh, Rekha Keshvara, Carla Jordan, Benjamin Jackson, Gwendoline Wilkes, Jason Appleton, Zhe Law, Oliver Matias, Evangelos Vasileiadis, Cathy Mason, Anthea Parry, Geraldine Landers, Melinda Holden, Basaam Aweid, Khalid Rashed, Linda Balian, Carinna Vickers, Elizabeth Keeling, Sarah Board, Joanna Allison, Clare Buckley, Barbara Williams-Yesson, Joanne Board, Tressy Pitt-Kerby, Alfonso Tanate, Diane Wood, Manohar Kini, Dinesh Chadha, Deborah Walstow, Rosanna Fong, Robert Luder, Tolu Adesina, Jill Gallagher, Hayley Bridger, Elodie Murali, Maneesh Bhargava, Chloe van Someren, Frances Harrington, Abhijit Mate, Ali James, Gillian Courtauld, Christine Schofield, Katja Adie, Linda Lucas, Kirsty Bond, Bev Maund, Sam Ellis, Paul Mudd, Martin James, Samantha Keenan, Angela Bowring, Julie Cageao, Hayley Kingwell, Caroline Roughan, Anthony Hemsley, Jane Sword, David Strain, Keniesha Miller, Anita Goff, Karin Gupwell, Kevin Thorpe, Hedley Emsley, Shuja Punekar, Alison McLoughlin, Sulaiman Sultan, Bindu Gregory, Sonia Raj, Donna Doyle, Keith Muir, Wilma Smith, Angela Welch, Fiona Moreton, Bharath Kumar Cheripelli, Salwa El Tawil, Dheeraj Kalladka, Xuya Huang, Nicola Day, Sankaranarayanan Ramachandran, Caroline Crosbie, Jennifer Elliot, Tony Rudd, Katherine Marks, Ajay Bhalla, Jonathan Birns, Sagal Kullane, Nic Weir, Christopher Allen, Vanessa Pressly, Pam Crawford, Emma Battersby-Wood, Alex Blades, Shuna Egerton, Ashleigh Walters, Sue Evans, James Richard Marigold, Fiona Smith, Gabriella Howard, Imogen Gartrell, Simon Smith, Robyn Creeden, Chloe Cox, Cherish Boxall, Jonathan Hewitt, Claire Nott, Procter Sarah, Jessica Whiteman, Steve Buckle, Rebecca Wallace, Rina Mardania, Jane Gray, Claire Triscott, Anand Nair, Jill Greig, Pratap Rana, Matthew Robinson, Mohammad Irfan Alam, David Werring, Duncan Wilson, Caroline Watchurst, Maria Brezitski, Luci Crook, Ifan Jones, Azra Banaras, Krishna Patel, Renuka Erande, Caroline Hogan, Isabel Hostettler, Amy Ashton, Shez Feerick, Nina Francia, Nnebuife Oji, Emma Elliott, Talal Al-Mayhani, Martin Dennis, Cathie Sudlow, William Whiteley, Dipankar Dutta, Pauline Brown, Deborah Ward, Fiona Davis, Jennifer Turfrey, Chloe Hughes, Kayleigh Collins, Rehana Bakawala, Susan O'Connell, Jon Glass, David Broughton, Dinesh Tryambake, Lynn Dixon, Kath Chapman, Andrew Young, Adrian Bergin, Andrew Sigsworth, Aravind Manoj, Glyn Fletcher, Paula Lopez, Penelope Cox, Mark Wilkinson, Paul Fitzsimmons, Nikhil Sharma, James Choulerton, Denise Button, Lindsey Dow, Lukuman Gbadamoshi, Joanne Avis, Barbara Madigan, Stephanie McCann, Louise Shaw, Deborah Howcroft, Suzanne Lucas, Andrew Stone, Gillian Cluckie, Caroline Lovelock, Brian Clarke, Neha Chopra, Natasha Clarke, Bhavini Patel, Kate Kennedy, Rebecca Williams, Adrian Blight, Joanna O'Reilly, Chukwuka Orefo, Nilofer Dayal, Rita Ghatala, Temi Adedoyin, Fran Watson, Sarah Trippier, Lillian Choy, Barry Moynihan, Usman Khan, Val Jones, Naomi Jeyaraj, Lourda Kerin, Kamy Thavanesan, Divya Tiwari, Chantel Cox, Anja Ljubez, Laura Tucker, Arshi Iqbal, Caroline Bagnall, Marketa Keltos, Josh Roberts, Becky Jupp, Catherine Ovington, Emily Rogers, Owen David, Jo Bell, Barbara Longland, Gail Hann, Martin Cooper, Mohammad Nasar, Anoja Rajapakse, Inez Wynter, Ijaz Anwar, Helen Skinner, Tarn Nozedar, Damian McArdle, Balakrishna Kumar, Susan Crawford, Arunkumar Annamalai, Alex Ramshaw, Clare Holmes, Sarah Caine, Mairead Osborn, Emily Dodd, Peter Murphy, Nicola Devitt, Pauline Baker, Amy Steele, Lucy Belle Guthrie, Samantha Clarke, Ahamad Hassan, Dean Waugh, Emelda Veraque, Linetty Makawa, Mary Kambafwile, Marc Randall, Vasileios Papavasileiou, Claire Cullen, Jenny Peters, Hlaing Thant, Tanya Ingram, Mellor Zoe, Ramesh Durairaj, Melanie Harrison, Sarah Stevenson, Daniela Shackcloth, Jordan Ewing, Victoria Sutton, Mark McCarron, Jacqueline McKee, Mandy Doherty, Ferghal McVerry, Caroline Blair, Mary MacLeod, Janice Irvine, Heather Gow, Jacqueline Furnace, Anu Joyson, Baljit Jagpal, Sarah Ross, Katrina Klaasen, Sandra Nelson, Rebecca Clarke, Nichola Crouch, Beverly MacLennan, Vicky Taylor, Daniel Epstein, Avani Shukla, Vinodh Krishnamurthy, Paul Nicholas, Sammie Qureshi, Adam Webber, Justin Penge, Hawraman Ramadan, Stuart Maguire, Chris Patterson, Ruth Bellfield, Brigid Hairsine, Kelvin Stewart, Michaela Hooley, Outi Quinn, Bella Richard, Sally Moseley, Mandy Edwards, Heidi Lawson, Michelle Tayler, Yogish Pai, Mahesh Dhakal, Bernard Esisi, Sofia Dima, Gemma Marie Smith, Mark Garside, Muhammad Naeem, Vidya Baliga, Gill Rogers, Ellen Brown, David Bruce, Rachel Hayman, Susan Clayton, Ed Gamble, Rebecca Grue, Bethan Charles, Adam Hague, Sujata Blane, Caroline Lambert, Afnan Chaudhry, Thomas Harrison, Kari Saastamoinen, Dionne Hove, Laura Howaniec, Gemma Grimwood, Ozlem Redjep, Fiona Humphries, Lucia Argandona, Larissa Cuenoud, Esther Erumere, Sageet Amlani, Grace Auld, Afraim Salek-Haddadi, Ursula Schulz, James Kennedy, Gary Ford, Philip Mathieson, Ian Reckless, Rachel Teal, Giulia Lenti, George Harston, Eoin O'Brien, Joanne Mcgee, Jennifer Mitchell, Elaine Amis, Dominic Handley, Siobhan Kelly, George Zachariah, Jobbin Francis, Sarah Crisp, Juliana Sesay, Sarah Finlay, Helen Hayhoe, Niamh Hannon, Tom Hughes, Bethan Morse, Henry De Berker, Emma Tallantyre, Ahmed Osman, Susan White, Stefan Schwarz, Benjamin Jelley, Rajendra Yadava, Khalid Azhar, Julie Reddan, Mirriam Sangombe, Samantha Stafford, Ken Fotherby, Debbie Morgan, Farrukh Baig, Karla Jennings-Preece, Donna Butler, Nasar Ahmad, Angela Willberry, Angela Stevens, Baljinder Rai, Prasad Siddegowda, Peter Howard, Lisa Hyatt, Tracey Dobson, David Jarrett, Suheil Ponnambath, Jane Tandy, Yasmin Harrington-Davies, Rebecca Butler, Claire James, Stacey Valentine, Anne Suttling, Peter Langhorne, Gillian Kerr, Fiona Wright, Ruth Graham, Christine McAlpine, Mohammad Shahzad Iqbal, Louise Humphreys, Kath Pasco, Olga Balazikova, Ashraf Nasim, Cassilda Peixoto, Louise Gallagher, Shahrzad Shahmehri, Sandip Ghosh, Elizabeth Barrie, Danielle Gilmour, Margo Henry, Tom Webb, Linda Cowie, Hannah Rudenko, Shanni McDonald, Natasha Schumacher, Susannah Walker, Tracey Cosier, Anna Verrion, Eva Beranova, Audrey Thomson, Marius Venter, Arindam Kar, Sheila Mashate, Kirsten Harvey, Léjeune Gardener, Vinh Nguyen, Omid Halse, Olivia Geraghty, Beth Hazel, Peter Wilding, Victoria Tilley, Tim Cassidy, Beverley McClelland, Maria Bokhari, Timothy England, Mohana Maddula, Richard Donnelly, Paul Findlay, Ashish Macaden, Ian Shread, Charlotte Barr, Azlisham Mohd Nor, Claire Brown, Nicola Persad, Charlotte Eglinton, Marie Weinling, Benjamin Hyams, Alex Shah, John Baker, Anthony Byrne, Caroline McGhee, Amanda Smart, Claire Copeland, Michael Carpenter, Marion Walker, Richard Davey, Ann Needle, Razik Fathima, Gavin Bateman, Prabal Datta, Andrew Stanners, Linda Jackson, Julie Ball, Michelle Davis, Natalie Atkinson, Michelle Fawcett, Teresa Thompson, Helen Guy, Valerie Hogg, Carole Hays, Stephen Woodward, Mohammad Haque, Eluzai Hakim, Stuart Symonds, Mehran Maanoosi, Jane Herman, Toby Black, Skelton Miriam, Caroline Clarke, Alpha Anthony, Michele Tribbeck, Julie Cronin, Denise Mead, Ruth Fennelly, James McIlmoyle, Christina Dickinson, Carol Jeffs, Sajjad Anwar, Joanne Howard, Kirsty Jones, Saikat Dhar, Caroline Clay, Muhammad Siddiq, Simone Ivatts, Yolanda Baird, Moore Sally, Isobel Amey, Sophie Newton, Lisa Clayton-Evans, Indra Chadbourn, Rayessa Rayessa, Charde Naylor, Alicia Rodgers, Lisa Wilson, Sarah Wilson, Emma Clarkson, Ruth Davies, Paula Owings, Graeme Sangster, Valerie Gott, Victoria Little, Pauline Weir, Suja Cherian, Deepa Jose, Helen Moroney, Susan Downham, Angela Dodd, Venetia Vettimootal Johnson, Laura Codd, Naomi Robinson, Ashraf Ahmed, Mo Albazzaz, Sharon Johnson, Carol Denniss, Mishell Cunningham, Tajammal Zahoor, Timothy Webster, Sandra Leason, Syed Haider, Kausic Chatterjee, Arumugam Nallasivan, Charlotte Perkins, Samantha Seagrave, Colin Jenkins, Fiona Price, Claire Hughes, Lily Mercer, Malik Hussain, Sarah Brown, Miriam Harvey, Jane Homan, Mohammad Khan, Robert Whiting, Leanne Foote, Nicholas Hunt, Helen Durman, Lucy Brotherton, Jayne Foot, Corinne Pawley, Eliza Foster, Alison Whitcher, Kneale Metcalf, Jenny Jagger, Susan McDonald, Kelly Waterfield, Patrick Sutton, Naval Shinh, Ajmal Anversha, Garth Ravenhill, Richard Greenwood, Janak Saada, Alison Wiltshire, Rebekah Perfitt, Sreeman Andole, Naveen Gadapa, Karen Dunne, Magdalini Krommyda, Evelyne Burssens, Sam King, Catherine Plewa, Nigel Smyth, Jenny Wilson, Elio Giallombardo, Lucy Sykes, Pradeep Kumar, James Barker, Isabel Huggett, Linda Dunn, Charlotte Culmsee, Philip Thomas, Min Myint, Helen Brew, Nikhil Majmudar, Janice OConnell, George Bunea, Charlotte Fox, Diane Gulliver, Andrew Smith, Betty Mokoena, Naweed Sattar, Ramesh Krishnamurthy, Emily Osborne, David Wilson, Belinda Wroath, Kevin Dynan, Michael Power, Susan Thompson, Victoria Adell, Enoch Orugun, Una Poultney, Rachel Glover, Hannah Crowther, Sarah Thornthwaite, Ivan Wiggam, Aine Wallace, Enda Kerr, Ailsa Fulton, Annemarie Hunter, Suzanne Tauro, Sarah Cuddy, David Mangion, Anne Hardwick, Skarlet Markova, Tara Lawrence, Carmen Constantin, Jo Fletcher, Isobel Thomas, Kerry Pettitt, Lakshmanan Sekaran, Margaret Tate, Kiranjit Bharaj, Rohan Simon, Frances Justin, Sakthivel Sethuraman, Duke Phiri, Niaz Mohammed, Meena Chauhan, Khaled Elfandi, Uzma Khan, David Eveson, Amit Mistri, Lisa Manning, Shagufta Khan, Champa Patel, Mohammed Moqsith, Saira Sattar, Man Yee Lam, Kashif Musarrat, Claire Stephens, Latheef Kalathil, Richard Miller, Maqsud Salehin, Nikki Gautam, Duncan Bailey, Kelly Amor, Julie Meir, Anne Nicolson, Javed Imam, Lisa Wood, Julie White, Mahmud Sajid, George Ghaly, Margaret Ball, Rachel Gascoyne, Harald Proeschel, Simon Sharpe, Sarah Horton, Emily Beaves, Stephanie Jones, Brigitte Yip, Murdina Bell, Linda MacLiver, Brian MacInnes, Don Sims, Jennifer Hurley, Mark Willmot, Claire Sutton, Edward Littleton, Susan Maiden, Rachael Jones, James Cunningham, Carole Green, Michelle Bates, Raj Shekhar, Ellie Gilham, Iman Ahmed, Rachel Crown, Tracy Fuller, Neetish Goorah, Angela Bell, Christine Kelly, Arun Singh, Jamie Walford, Benjamin Tomlinson, Farzana Patel, Stephen Duberley, Ingrid Kane, Chakravarthi Rajkumar, Jane Gaylard, Joanna Breeds, Nicola Gainsborough, Alexandra Pitt-Ford, Emma Barbon, Laura Latter, Philip Thompson, Simon Hervey, Shrivakumar Krishnamoorthy, Joseph Vassallo, Deborah Walter, Helen Cochrane, Meena Srinivasan, Robert Campbell, Denise Donaldson, Nichola Motherwell, Frances Hurford, Indranil Mukherjee, Antony Kenton, Sheila Nyabadza, Irene Martin, Benjamin Hunt, Hardi Hassan, Sarah O'Toole, Bander Dallol, Janet Putterill, Ratneshwari Jha, Rachel Gallifent, Puneet Kakar, Aparna Pusalkar, kelly Chan, Puneet Dangri, Hannah Beadle, Angela Cook, Karen Crabtree, Santhosh Subramonian, Peter Owusu-Agyei, Natalie Temple, Nicola Butterworth-Cowin, Suzanne Ragab, Kerstin Knops, Emma Jinks, Christine Dickson, Laura Gleave, Judith Dube, Jacqui Leggett, Tatiana Garcia, Sissy Ispoglou, Rachel Evans, Sandeep Ankolekar, Anne Hayes, Hlaing Ni, Bithi Rahman, Josette Milligan, Carol Graham, Josin Jose, Breffni Keegan, Jim Kelly, Richard Dewar, James White, Kelly Thomas, Rajkumar, C, University of St Andrews. School of Medicine, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Population and Behavioural Science Division, University of St Andrews. Pure Mathematics, University of St Andrews. School of Psychology and Neuroscience, and University of St Andrews. School of Biology

Subjects
Male, MICROBLEEDS, 030204 cardiovascular system & hematology, AMYLOID ANGIOPATHY, Brain Ischemia, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Secondary Prevention, ACUTE ISCHEMIC-STROKE, Aged, 80 and over, Aspirin, Manchester Cancer Research Centre, medicine.diagnostic_test, Hazard ratio, Brain, Magnetic Resonance Imaging, Superficial siderosis, Cerebral Small Vessel Diseases, Stroke, Treatment Outcome, Female, medicine.drug, CT, medicine.medical_specialty, ANTITHROMBOTIC THERAPY, Clinical Neurology, Neuroimaging, Subgroup analysis, 03 medical and health sciences, Internal medicine, medicine, Journal Article, Humans, Aged, Cerebral Hemorrhage, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, DAS, Magnetic resonance imaging, medicine.disease, SIGNS, ASPIRIN, Neurology (clinical), Tomography, X-Ray Computed, business, SUPERFICIAL SIDEROSIS, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery
Abstract

Background: Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy.Methods: RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627.Findings: Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08–1·13] vs 0·77 [0·13–4·61]; pinteraction=0·41), cerebral microbleed number 0–1 versus 2–4 versus 5 or more (HR 0·77 [0·13–4·62] vs 0·32 [0·03–3·66] vs 0·33 [0·07–1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004–6·79] vs 0·37 [0·09–1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05).Interpretation: Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision.Funding: British Heart Foundation.

Published
2019
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3. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Christopher Price, P. J. A. M. Brouwers, Vincent Thijs, Sze Ho Ma, Mark Schembri, Raymond T.F. Cheung, Christopher Karayiannis, Werner H. Mess, Robert Simister, Peter Wilkinson, Jayesh Modi Medanta, Janice E. O’Connell, Karen Ma, Martin Dennis, Sean C. Murphy, John Ly, Velandai Srikanth, Hing Lung Ip, Mathew Burn, Saima Hilal, Ijaz Anwar, Richard Shek-kwan Chang, Christopher Chen, Carmen Barbato, Hatice Ozkan, Achim Gass, Louise Shaw, Hen Hallevi, Aravindakshan Manoj, Julie Staals, Frances Harrington, Henry Houlden, Hideo Hara, Kam Tat Leung, Christopher Traenka, Jeroen Hendrikse, Keon-Joo Lee, Elio Giallombardo, Ender Uysal, Edmund Ka Ming Wong, Joost Jöbsis, Gargi Banerjee, Dulka Manawadu, Rebeca Marín, John S. Thornton, Nick S. Ward, Vinodh Krishnamurthy, Thomas W. Leung, Ji Hoe Heo, Philippe Maeder, Masatoshi Koga, Michael Power, Marc Randall, Amos D. Korczyn, Narayanaswamy Venketasubramanian, Derya Selcuk Demirelli, Richard Li, Prabel Datta, Christine Guevarra, YK Wong, Ysoline Beigneux, Cisca Linn, Solveig Horstmann, Henk Verbiest, Kirsty Harkness, Eric Vicaut, John Coyle, Shoichiro Sato, Anne Marie Mendyk, Chathuri Yatawara, Alexandros A Polymeris, Lisa Hert, Joan Martí-Fàbregas, Felix Fluri, Cathy Soufan, Djamil Vahidassr, Lakshmanan Sekaran, Chu Peng Hoi, Maarten van Gemert, Andreas Charidimou, Robert Luder, Lillian Choy, Jaap van der Sande, Hannah Cohen, Jae-Sung Lim, Maam Mamun, Vincent I.H. Kwa, Kyohei Fujita, Joseph Kwan, Syuhei Ikeda, John Mitchell, Paul Berntsen, Michael J. Thrippleton, Shelagh B. Coutts, Simone Browning, Paul Guyler, Heinrich Mattle, Elles Douven, Jonathan Birns, M. Eline Kooi, Jan Stam, Hedley C. A. Emsley, David Mangion, David Calvet, Min Lou, Yannie Soo, Santiago Medrano-Martorell, Michael G. Hennerici, Chris Moran, Thomas Gattringer, Bernard Esisi, Kazuhisa Yoshifuji, Hakan Ay, Rustam Al-Shahi Salman, Joanna M. Wardlaw, Derek Hayden, Richard J. Perry, Gunaratam Gunathilagan, Hans Rolf Jäger, Frank-Erik de Leeuw, Luis Prats-Sánchez, Pankaj Sharma, Mi Hwa Yang, Marie Yvonne Douste-Blazy, Enas Lawrence, Nils Peters, Elisa Merino, KC Teo, Ethem Murat Arsava, Luc Bracoub, Dinesh Chadha, Linxin Li, Nikola Sprigg, Adrian R Parry-Jones, Pascal P. Gratz, Siu Hung Li, Stephen Makin, Arumug Nallasivam, Jane Sword, Mauro S.B. Silva, Ping Wing Ng, Layan Akijian, Krishna A Dani, Sebastian Thilemann, Marie Dominique Fratacci, Gareth Ambler, Nagaendran Kandiah, Lee-Anne Slater, Ilse Burger, Kath Pasco, Paul J. Nederkoorn, Suk Fung Tsang, Tae Jin Song, Henry Ma, Kaori Miwa, Keith W. Muir, Susana Muñoz-Maniega, Jihoon Kang, Nicolas Christ, Beom Joon Kim, Noortje A.M. Maaijwee, Kwok Kui Wong, Jon Scott, Leonidas Panos, Oi Ling Chan, Shigeru Inamura, Prasanna Aghoram, David Hargroves, Lino Ramos, Ying Zhou, Chung Yan Chan, Masayuki Shiozawa, Eleni Sakka, Michelle Davis, Matthew Smith, Leo H. Bonati, Dilek Necioglu Orken, Toshihiro Ide, Jaap Kappelle, Ale Algra, Charlotte Zerna, Laurence Legrand, Eric Jouvent, Roland Veltkamp, Simon Jung, Zeynep Tanriverdi, Shahoo Singhal, Sarah Caine, Natan M. Bornstein, Régis Bordet, Anil M. Tuladhar, Maarten Schrooten, John F. Corrigan, Alexander P. Leff, Kazunori Toyoda, Mathuri Prabhakaran, Kim Wiegertjes, Eunbin Ko, Wouter Schoonewille, Sebastian Köhler, Yvo B.W.E.M. Roos, Wing Chi Fong, Jun Tanaka, Abduelbaset Elmarim, Syed Mansoor, Peter J. Koudstaal, Kari Saastamoinen, Eric E. Smith, Paul O'Mahony, Hugues Chabriat, Duncan Wilson, Appu Suman, Dianne H.K. van Dam-Nolen, Parashkev Nachev, Ahamad Hassan, Maria del C. Valdés Hernández, Clare Shakeshaft, Stefan T. Engelter, James Okwera, Aad van der Lugt, Els De Schryver, Stef Bakker, Azlisham Mohd Nor, Yusuke Yakushiji, Robert J. van Oostenbrugge, Claire Cullen, Man Yu Tse, Sebastian Eppinger, Gregory Y.H. Lip, Kotaro Iida, Efrat Kliper, Bibek Gyanwali, Elizabeth A. Warburton, Hee-Joon Bae, Thanh G. Phan, Tarek A. Yousry, Henrik Gensicke, Christine Delmaire, Jean-Louis Mas, Jill Abrigo, Fiona Carty, Jan C. Purrucker, Masashi Nishihara, Leopold Hertzberger, Joachim Fladt, Einor Ben Assayag, Simon Leach, Winnie C.W. Chu, Edward S. Hui, Bonnie Y.K. Lam, Moon Ku Han, Francesca M Chappell, David Williams, Robin Lemmens, Philippe Lyrer, Hiroyuki Irie, Raquel Delgado-Mederos, Ronil V. Chandra, Nigel Smyth, Henry K.F. Mak, Young Dae Kim, Ryan Hoi Kit Cheung, Beatriz Gómez-Ansón, Fidel Nuñez, Anna K. Heye, Adrian Barry, Janet Putterill, Mark White, Alejandro Martínez-Domeño, Vincent Mok, Rachel Marsh, Mahmud Sajid, Timothy J. England, SL Ho, Christopher Patterson, Daniel Guisado-Alonso, Peter J. Kelly, Lawrence K.S. Wong, Anthea Parry, Enrico Flossman, Chao Xu, Marwan El-Koussy, Karim Mahawish, Sissi Ispoglou, Franz Fazekas, Toshio Imaizumi, David J. Seiffge, Wenyan Liu, Chahin Pachai, Adrian Wong, Khaled Darawil, Jeremy Molad, Sanjeevikumar Meenakishundaram, Enrico Flossmann, Harald Proschel, Caroline E. Lovelock, Christine Roffe, Kui Kai Lau, Michael McCormick, Peter M. Rothwell, Paul A. Armitage, Sarah Gunkel, Myung Suk Jang, Martin Cooper, Pol Camps-Renom, Martin M. Brown, David Cohen, David J. Werring, Koon-Ho Chan, Deborah Kelly, Neurology, ACS - Atherosclerosis & ischemic syndromes, ANS - Neurovascular Disorders, Division 2, Radiology & Nuclear Medicine, RS: Carim - B06 Imaging, Beeldvorming, MUMC+: DA BV Klinisch Fysicus (9), RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: CARIM - R3.11 - Imaging, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, RS: Carim - B05 Cerebral small vessel disease, RS: CARIM - R3.03 - Cerebral small vessel disease, and MUMC+: MA Med Staf Spec Neurologie (9)

Subjects
INTRACEREBRAL HEMORRHAGE, 030204 cardiovascular system & hematology, AMYLOID ANGIOPATHY, PREDICT, Brain Ischemia, 0302 clinical medicine, SMALL VESSEL DISEASE, Medicine, CHINESE PATIENTS, 10. No inequality, Stroke, medicine.diagnostic_test, DEMENTIA, Hazard ratio, Absolute risk reduction, Brain, Atrial fibrillation, ASSOCIATION, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Magnetic Resonance Imaging, 3. Good health, Ischemic Attack, Transient, Cardiology, Life Sciences & Biomedicine, Intracranial Hemorrhages, medicine.drug, Cohort study, medicine.medical_specialty, RECURRENT STROKE, Clinical Neurology, 610 Medicine & health, Neuroimaging, Article, WARFARIN, 03 medical and health sciences, Internal medicine, Journal Article, Humans, Intracerebral hemorrhage, Science & Technology, business.industry, Warfarin, Magnetic resonance imaging, T2-ASTERISK-WEIGHTED MR-IMAGES, medicine.disease, ATRIAL-FIBRILLATION, Neurosciences & Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 208975.pdf (Publisher’s version ) (Open Access) BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2.45 (1.82-3.29) for intracranial haemorrhage and 1.23 (1.08-1.40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4.55 [95% CI 3.08-6.72] for intracranial haemorrhage vs 1.47 [1.19-1.80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5.52 [3.36-9.05] vs 1.43 [1.07-1.91]; and for >/=20 cerebral microbleeds, aHR 8.61 [4.69-15.81] vs 1.86 [1.23-1.82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for >/=20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING: British Heart Foundation and UK Stroke Association.

Published
2019
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