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1. Potential missed opportunities to prevent ischaemic stroke: prospective multicentre cohort study of atrial fibrillation-associated ischaemic stroke and TIA

Author: Gregory Y H Lip, Michael Power, Martin M Brown, Matthew Smith, Christopher Price, Tarek Yousry, Gargi Banerjee, David J Werring, Gareth Ambler, Michelle Davis, Chris Patterson, Keith Muir, Krishna Dani, Julie Staals, Jon Scott, Pankaj Sharma, Duncan Wilson, Clare Shakeshaft, Hannah Cohen, Kirsty Harkness, Louise Shaw, Jane Sword, Roland Veltkamp, Deborah Kelly, Frances Harrington, Marc Randall, Karim Mahawish, Abduelbaset Elmarim, Bernard Esisi, Claire Cullen, Arumug Nallasivam, Adrian Barry, Christine Roffe, John Coyle, Ahamad Hassan, Caroline Lovelock, Jonathan Birns, David Cohen, L Sekaran, Adrian Parry-Jones, Anthea Parry, David Hargroves, Harald Proschel, Prabel Datta, Khaled Darawil, Aravindakshan Manoj, Mathew Burn, Elio GialloMbardo, Nigel Smyth, Syed Mansoor, Ijaz Anwar, Rachel Marsh, Sissi Ispoglou, Dinesh Chadha, Mathuri Prabhakaran, Sanjeevikumar Meenakishundaram, Vinodh Krishnamurthy, Prasanna Aghoram, Michael McCormick, Nikola Sprigg Paul O’Mahony, Peter Wilkinson, Simon Leach, Sarah Caine, Ilse Burger, Gunaratam Gunathilagan, Paul Guyler, Hedley Emsley, Dulka Manawadu, Kath Pasco, Maam Mamun, Robert Luder, Mahmud Sajid, James Okwera, Elizabeth Warburton, Kari Saastamoinen, Timothy England, Janet Putterill, Enrico Flossman, David Mangion, Appu Suman, John Corrigan, Enas Lawrence, Djamil Vahidassr, Janice O’Connell, Mark White, Martin Cooper, Lillian Choy, David Seiffge, Andreas Charidimou, H R Jäger, Azlisham Mohd Nor, and Al-Shahi Salman Rustam
Subjects: Medicine
Abstract: Objective We report on: (1) the proportion of patients with known atrial fibrillation (AF); and (2) demographic, clinical or radiological differences between patients with known AF (and not treated) and patients with newly diagnosed AF, in a cohort of patients who presented with ischaemic stroke or transient ischaemic attack (TIA) not previously treated with anticoagulation.Design We reviewed cross-sectional baseline demographic and clinical data from a prospective observational cohort study, (CROMIS-2).Setting Patients were recruited from 79 hospital stroke centres throughout the UK and one centre in the Netherlands.Participants Patients were eligible if they were adults who presented with ischaemic stroke or TIA and AF and had not been previously treated with oral anticoagulation.Main outcome measures Proportion of patients with known AF before index ischaemic stroke or TIA from a cohort of patients who have not been previously treated with oral anticoagulation. Secondary analysis includes the comparison of CHA2DS2-VASc and HAS-BLED scores and other demographics and risk factors between those with newly diagnosed AF and those with previously known AF.Results Of 1470 patients included in the analysis (mean age 76 years (SD 10)), 622 (42%) were female; 999 (68%) patients had newly diagnosed AF and 471 (32%) patients had known AF. Of the 471 patients with known AF, 68% had a strong indication for anticoagulation and 89% should have been considered for anticoagulation based upon CHA2DS2-VASc score. Patients with known AF were more likely to have a prior history of dementia (4% vs 2%, p=0.02) and had higher HAS-BLED scores (median 3 vs 2). CHA2DS2-VASc, other risk factors and demographics were similar.Conclusions About 1/3 of patients who present with stroke and have AF who have not been treated with oral anticoagulation have previously known AF. Of these patients, at least 68% were not adequately treated with oral anticoagulation.Trial registration number NCT02513316.
Published: 2019
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2. Practical '1-2-3-4-Day' Rule for Starting Direct Oral Anticoagulants After Ischemic Stroke With Atrial Fibrillation: Combined Hospital-Based Cohort Study

Author: Shunsuke Kimura, Kazunori Toyoda, Sohei Yoshimura, Kazuo Minematsu, Masahiro Yasaka, Maurizio Paciaroni, David J. Werring, Hiroshi Yamagami, Takehiko Nagao, Shinichi Yoshimura, Alexandros Polymeris, Annaelle Zietz, Stefan T. Engelter, Bernd Kallmünzer, Manuel Cappellari, Tetsuya Chiba, Takeshi Yoshimoto, Masayuki Shiozawa, Takanari Kitazono, Masatoshi Koga, Kenichi Todo, Kazumi Kimura, Yoshiki Yagita, Eisuke Furui, Ryo Itabashi, Tadashi Terasaki, Yoshiaki Shiokawa, Teruyuki Hirano, Kenji Kamiyama, Jyoji Nakagawara, Shunya Takizawa, Kazunari Homma, Satoshi Okuda, Yasushi Okada, Keisuke Tokunaga, Tomoaki Kameda, Kazuomi Kario, Yoshinari Nagakane, Yasuhiro Hasegawa, Hisanao Akiyama, Satoshi Shibuya, Hiroshi Mochizuki, Yasuhiro Ito, Takahiro Nakashima, Hideki Matsuoka, Kazuhiro Takamatsu, Kazutoshi Nishiyama, Shoichiro Sato, Shoji Arihiro, Manabu Inoue, Masahito Takagi, Kanta Tanaka, Kazuyuki Nagatsuka, Takenori Yamaguchi, Yoichiro Hashimoto, Kiyohiro Houkin, Kazuo Kitagawa, Masayasu Matsumoto, Norio Tanahashi, Yasuo Terayama, Shinichiro Uchiyama, Etsuro Mori, Yutaka Furukawa, Takeshi Kimura, Yoshiaki Kumon, Ken Nagata, Shigeru Nogawa, Tomohiro Sakamoto, Toshinori Hirai, Kohsuke Kudo, Makoto Sasaki, Shotai Kobayashi, Toshimitsu Hamasaki, Michela Giustozzi, Monica Acciarresi, Giancarlo Agnelli, Valeria Caso, Fabio Bandini, Georgios Tsivgoulis, Shadi Yaghi, Karen L. Furie, Prasanna Tadi, Cecilia Becattini, Marialuisa Zedde, Azmil H Abdul-Rahim, Kennedy R Lees, Andrea Alberti, Michele Venti, Cataldo D’Amore, Maria Giulia Mosconi, Ludovica Anna Cimini, Paolo Bovi, Monica Carletti, Alberto Rigatelli, Jukka Putaala, Liisa Tomppo, Turgut Tatlisumak, Simona Marcheselli, Alessandro Pezzini, Loris Poli, Alessandro Padovani, Vieri Vannucchi, Sung-Il Sohn, Gianni Lorenzini, Rossana Tassi, Francesca Guideri, Maurizio Acampa, Giuseppe Martini, George Ntaios, George Athanasakis, Konstantinos Makaritsis, Efstathia Karagkiozi, Konstantinos Vadikolias, Chrissoula Liantinioti, Maria Chondrogianni, Nicola Mumoli, Franco Galati, Simona Sacco, Cindy Tiseo, Francesco Corea, Walter Ageno, Marta Bellesini, Giovanna Colombo, Giorgio Silvestrelli, Alfonso Ciccone, Alessia Lanari, Umberto Scoditti, Licia Denti, Michelangelo Mancuso, Miriam Maccarrone, Leonardo Ulivi, Giovanni Orlandi, Nicola Giannini, Tiziana Tassinari, Maria Luisa De Lodovici, Christina Rueckert, Antonio Baldi, Danilo Toni, Federica Letteri, Martina Giuntini, Enrico Maria Lotti, Yuriy Flomin, Alessio Pieroni, Odysseas Kargiotis, Theodore Karapanayiotides, Serena Monaco, Mario Maimone Baronello, Laszló Csiba, Lilla Szabó, Alberto Chiti, Elisa Giorli, Massimo Del Sette, Davide Imberti, Dorjan Zabzuni, Boris Doronin, Vera Volodina, Patrik Michel, Peter Vanacker, Kristian Barlinn, Lars-Peder Pallesen, Jessica Barlinn, Dirk Deleu, Gayane Melikyan, Faisal Ibrahim, Naveed Akhtar, Vanessa Gourbali, Luca Masotti, Adrian Parry-Jones, Chris Patterson, Christopher Price, Abduelbaset Elmarimi, Anthea Parry, Arumug Nallasivam, Azlisham Mohd Nor, Bernard Esis, David Bruce, Christine Roffe, Clare Holmes, David Cohen, David Hargroves, David Mangion, Dinesh Chadha, Djamil Vahidassr, Dulka Manawadu, Elio Giallombardo, Elizabeth Warburton, Enrico Flossman, Gunaratam Gunathilagan, Harald Proschel, Hedley Emsley, Ijaz Anwar, James Okwera, Janet Putterill, Janice O’Connell, John Bamford, John Corrigan, Jon Scott, Jonathan Birns, Karen Kee, Kari Saastamoinen, Kath Pasco, Krishna Dani, Lakshmanan Sekaran, Lillian Choy, Liz Iveson, Maam Mamun, Mahmud Sajid, Martin Cooper, Matthew Burn, Matthew Smith, Michael Power, Michelle Davis, Nigel Smyth, Roland Veltkamp, Pankaj Sharma, Paul Guyler, Paul O’Mahony, Peter Wilkinson, Prabel Datta, Prasanna Aghoram, Rachel Marsh, Robert Luder, Sanjeevikumar Meenakishundaram, Santhosh Subramonian, Simon Leach, Sissi Ispoglou, Sreeman Andole, Timothy England, Aravindakshan Manoj, Frances Harrington, Habib Rehman, Jane Sword, Julie Staals, Karim Mahawish, Kirsty Harkness, Louise Shaw, Michael McCormich, Nikola Sprigg, Syed Mansoor, Vinodh Krishnamurthy, Philippe A Lyrer, Leo H Bonati, David J Seiffge, Christopher Traenka, Nils Peters, Gian Marco De Marchis, Sebastian Thilemann, Nikolaos S Avramiotis, Henrik Gensicke, Lisa Hert, Benjamin Wagner, Fabian Schaub, Louisa Meya, Joachim Fladt, Tolga Dittrich, Urs Fisch, Bruno Bonetti, Giampaolo Tomelleri, Nicola Micheletti, Cecilia Zivelonghi, Andrea Emiliani, Kosmas Macha, Gabriela Siedler, Svenja Stoll, Ruihao Wang, Bastian Volbers, Stefan Schwab, David Haupenthal, and Luise Gaßmann
Subjects: Advanced and Specialized Nursing, acute ischemic stroke, Time Factors, Administration, Oral, Anticoagulants, Hemorrhage, cardioembolism, Hospitals, United States, Brain Ischemia, anticoagulation, atrial fibrillation, stroke prevention, Cohort Studies, Stroke, Treatment Outcome, Ischemic Attack, Transient, Atrial Fibrillation, Humans, Prospective Studies, Neurology (clinical), Cardiology and Cardiovascular Medicine, Ischemic Stroke
Abstract: Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.
Published: 2022
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3. Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author: Henry Ma, Eleni Sakka, Hugues Chabriat, Duncan Wilson, Appu Suman, Peter J. Kelly, SL Ho, Charlotte Zerna, Eric Jouvent, Lawrence K.S. Wong, Anthea Parry, Frances Harrington, Jan Stam, Christopher Patterson, Rustam Al-Shahi Salman, Shigeru Inamura, Krishna A Dani, Henry Houlden, Sebastian Thilemann, Kotaro Iida, Chao Xu, Eunbin Ko, Daniel Guisado-Alonso, Urs Fischer, Caroline E. Lovelock, Man Yu Tse, Wing Chi Fong, Azlisham Mohd Nor, Clare Shakeshaft, Philippe Maeder, Henrik Gensicke, Stefan T. Engelter, James Okwera, Christopher Chen, Dulka Manawadu, John F. Corrigan, Efrat Kliper, Shelagh B. Coutts, Alexander P. Leff, Kam Tat Leung, Chathuri Yatawara, Leopold Hertzberger, M. Eline Kooi, Kazuhisa Yoshifuji, Hing Lung Ip, Keon-Joo Lee, Sanjeevikumar Meenakishundaram, Hiroyuki Irie, Marc Randall, Hatice Ozkan, Hideo Hara, Jill Abrigo, Raquel Delgado-Mederos, Shaloo Singhal, Enrico Flossmann, Beatriz Gómez-Ansón, Paul O'Mahony, Carmen Barbato, Ahamad Hassan, Francesca M Chappell, Harald Proschel, Vincent Mok, Masashi Nishihara, Lakshmanan Sekaran, Derya Selcuk Demirelli, Chu Peng Hoi, Hakan Ay, Joan Martí-Fàbregas, Rebeca Marín, Anne Cristine Guevarra, Martin Cooper, Einor Ben Assayag, Anne-Marie Mendyk, Christine Roffe, Myung Suk Jang, Maarten van Gemert, Hannah Cohen, Jae-Sung Lim, YK Wong, Bonnie Y.K. Lam, Janet Putterill, Wouter Schoonewille, Nick S. Ward, Nikola Sprigg, Kui Kai Lau, Bernard Esisi, Peter M. Rothwell, Henk Verbiest, Kirsty Harkness, Elisa Merino, Gareth Ambler, Arumug Nallasivam, Nigel Smyth, Paul A. Armitage, Heinrich Mattle, Pol Camps-Renom, Martin M. Brown, David Cohen, Min Lou, Pankaj Sharma, Sarah Gunkel, Elles Douven, Andreas Charidimou, Djamil Vahidassr, Cathy Soufan, Alexandros A Polymeris, Michael G. Hennerici, Chris Moran, Rachel Marsh, Mahmud Sajid, Kyohei Fujita, David J. Werring, Joanna M. Wardlaw, Derek Hayden, Joseph Kwan, Timothy J. England, Jaap van der Sande, Luis Prats-Sánchez, Paul Guyler, Ryan Hoi Kit Cheung, Koon-Ho Chan, Frank-Erik de Leeuw, Simone Browning, Jon Scott, Adrian Barry, Alejandro Martínez-Domeño, Luc Bracoub, Dinesh Chadha, Ijaz Anwar, Deborah Kelly, Moon-Ku Han, Anil M. Tuladhar, Thomas Gattringer, Fiona Carty, Abduelbaset Elmarim, Syed Mansoor, Enrico Flossman, Dilek Necioglu Orken, Jane Sword, Velandai Srikanth, Ping Wing Ng, Thomas W. Leung, Richard Shek-kwan Chang, Hans Rolf Jäger, Marwan El-Koussy, Jeroen Hendrikse, Khaled Darawil, Kazunori Toyoda, Mathuri Prabhakaran, Karim Mahawish, Ethem Murat Arsava, Jihoon Kang, Kwok Kui Wong, Michael Power, Felix Fluri, Enas Lawrence, Maam Mamun, Sissi Ispoglou, Mathew Burn, Siu Hung Li, Henry K.F. Mak, Kaori Miwa, Els De Schryver, Franz Fazekas, Jonathan G. Best, Louise Shaw, Hen Hallevi, Keith W. Muir, Ilse Burger, Adrian Wong, Nils Peters, Susana Muñoz-Maniega, Yusuke Yakushiji, David Calvet, Mark White, Michael McCormick, Vinodh Krishnamurthy, David Hargroves, Jan C. Purrucker, Tae Jin Song, Masayuki Shiozawa, Noortje A.M. Maaijwee, Prasanna Aghoram, Nicolas Christ, Lino Ramos, Yannie Soo, Thanh G. Phan, Parashkev Nachev, David J. Seiffge, Kim Wiegertjes, Leo H. Bonati, Chahin Pachai, Oi Ling Chan, Yvo B.W.E.M. Roos, Santiago Medrano-Martorell, Natan M. Bornstein, Elizabeth A. Warburton, Richard Li, Prabel Datta, Pascal P. Gratz, Edmund Ka Ming Wong, Hedley C. A. Emsley, Marie-Yvonne Douste-Blazy, Gunaratam Gunathilagan, Nagaendran Kandiah, Masatoshi Koga, Roland Veltkamp, Lee-Anne Slater, Suk Fung Tsang, Beom Joon Kim, Simon Jung, Zeynep Tanriverdi, Sarah Caine, Peter J. Koudstaal, Laurence Legrand, Kari Saastamoinen, Ale Algra, Jean-Louis Mas, Christine Delmaire, Fidel Nuñez, Robert J. van Oostenbrugge, Sebastian Eppinger, Lillian Choy, Robert Luder, Vincent I.H. Kwa, Aad van der Lugt, Marie Dominique Fratacci, Stephen Makin, Layan Akijian, Régis Bordet, Mi Hwa Yang, Ying Zhou, Elio Giallombardo, Adrian R Parry-Jones, John S. Thornton, Amos D. Korczyn, Narayanaswamy Venketasubramanian, David J. Williams, Aravindakshan Manoj, Julie Staals, Solveig Horstmann, Dianne H.K. van Dam-Nolen, Claire Cullen, Benjamin Wagner, Jun Tanaka, Martin Dennis, Stef Bakker, Gregory Y.H. Lip, L. Jaap Kappelle, Robin Lemmens, Achim Gass, David Mangion, Matthew Smith, Toshio Imaizumi, Wenyan Liu, Jeremy Molad, Christopher Price, Paul J. Nederkoorn, P. J. A. M. Brouwers, Vincent Thijs, Sze Ho Ma, Mark Schembri, Peter Wilkinson, Janice E. O’Connell, Karen Ma, John Ly, Leonidas Panos, Chung Yan Chan, Toshihiro Ide, Christopher Traenka, Joost Jöbsis, Gargi Banerjee, Paul Berntsen, Michael J. Thrippleton, Raymond T.F. Cheung, Christopher Karayiannis, Werner H. Mess, Robert Simister, Jayesh Modi Medanta, Syuhei Ikeda, John Mitchell, Linxin Li, Mauro S.B. Silva, Eric Vicaut, John Coyle, Shoichiro Sato, Michelle Davis, Jonathan Birns, Richard J. Perry, Sean M. Murphy, KC Teo, Maria del C. Valdés Hernández, Bibek Gyanwali, Tarek A. Yousry, Kath Pasco, Sebastian Köhler, Joachim Fladt, Edward S. Hui, Philippe Lyrer, Young Dae Kim, Anna K. Heye, Eric E. Smith, Saima Hilal, Ender Uysal, Ji Hoe Heo, Ysoline Beigneux, Cisca Linn, Hee-Joon Bae, Simon Leach, Winnie C.W. Chu, Ronil V. Chandra, Neurology, ACS - Atherosclerosis & ischemic syndromes, ANS - Neurovascular Disorders, MUMC+: HZC Med Staf Spec Klinische Neurofys (9), RS: Carim - B06 Imaging, MUMC+: HZC Klinische Neurofysiologie (5), Klinische Neurowetenschappen, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Neurologie (3), RS: Carim - B05 Cerebral small vessel disease, MUMC+: Hersen en Zenuw Centrum (3), MUMC+: MA Med Staf Spec Neurologie (9), RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, Beeldvorming, and MUMC+: DA BV Klinisch Fysicus (9)
Subjects: Adult, Male, Risk, EXTERNAL VALIDATION, medicine.medical_specialty, Neurology, MODELS, Clinical Neurology, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Recurrence, Internal medicine, Antithrombotic, Humans, Medicine, Prospective cohort study, 610 Medicine & health, Stroke, METAANALYSIS, Aged, Ischemic Stroke, Science & Technology, medicine.diagnostic_test, business.industry, Proportional hazards model, Magnetic resonance imaging, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], medicine.disease, Magnetic Resonance Imaging, Ischemic Attack, Transient, ATRIAL-FIBRILLATION, Cardiology, Female, Neurology (clinical), Neurosciences & Neurology, business, Intracranial Hemorrhages, Life Sciences & Biomedicine, 030217 neurology & neurosurgery, Fibrinolytic agent, Cohort study
Abstract: Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.
Published: 2021
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4. Small Vessel Disease and Ischemic Stroke Risk During Anticoagulation for Atrial Fibrillation After Cerebral Ischemia

Author: Houwei Du, Duncan Wilson, Gareth Ambler, Gargi Banerjee, Clare Shakeshaft, Hannah Cohen, Tarek Yousry, Rustam Al-Shahi Salman, Gregory Y.H. Lip, Henry Houlden, Martin M. Brown, Keith W. Muir, Hans Rolf Jäger, David J. Werring, Adrian Parry-Jones, Chris Patterson, Christopher Price, Abduelbaset Elmarimi, Anthea Parry, Arumug Nallasivam, Azlisham Mohd Nor, Bernard Esisi, David Bruce, Biju Bhaskaran, Christine Roffe, Claire Cullen, Clare Holmes, David Cohen, David Hargroves, David Mangion, Dinesh Chadha, Djamil Vahidassr, Dulka Manawadu, Elio Giallombardo, Elizabeth Warburton, Enrico Flossman, Gunaratam Gunathilagan, Harald Proschel, Hedley Emsley, Ijaz Anwar, Ilse Burger, James Okwera, Janet Putterill, Janice O’Connell, John Bamford, John Corrigan, Jon Scott, Jonathan Birns, Karen Kee, Kari Saastamoinen, Kath Pasco, Krishna Dani, Lakshmanan Sekaran, Lillian Choy, Liz Iveson, Maam Mamun, Mahmud Sajid, Martin Cooper, Mathew Burn, Matthew Smith, Michael Power, Michelle Davis, Nigel Smyth, Roland Veltkamp, Pankaj Sharma, Paul Guyler, Paul O’Mahony, Peter Wilkinson, Prabel Datta, Prasanna Aghoram, Rachel Marsh, Robert Luder, Sanjeevikumar Meenakishundaram, Santhosh Subramonian, Simon Leach, Sissi Ispoglou, Sreeman Andole, Timothy England, Aravindakshan Manoj, Harrington Frances, Habib Rehman, Jane Sword, Julie Staals, Karim Mahawish, Kirsty Harkness, Louise Shaw, Michael McCormick, Nikola Sprigg, Syed Mansoor, and Vinodh Krishnamurthy
Subjects: Male, medicine.medical_specialty, brain, Small vessel occlusion, Ischemia, Disease, Brain Ischemia, White matter, Recurrence, Internal medicine, Atrial Fibrillation, medicine, Humans, ischemic attack, transient, atrial fibrillation, anticoagulation, Aged, Ischemic Stroke, Aged, 80 and over, Advanced and Specialized Nursing, business.industry, Atrial fibrillation, Middle Aged, medicine.disease, medicine.anatomical_structure, Cerebral Small Vessel Diseases, Ischemic stroke, Cardiology, Female, Neurology (clinical), Small vessel, Cardiology and Cardiovascular Medicine, business, white matter
Abstract: Background and Purpose: The causes of recurrent ischemic stroke despite anticoagulation for atrial fibrillation are uncertain but might include small vessel occlusion. We investigated whether magnetic resonance imaging markers of cerebral small vessel disease (SVD) are associated with ischemic stroke risk during follow-up in patients anticoagulated for atrial fibrillation after recent ischemic stroke or transient ischemic attack. Methods: We analyzed data from a prospective multicenter inception cohort study of ischemic stroke or transient ischemic attack anticoagulated for atrial fibrillation (CROMIS-2 [Clinical Relevance of Microbleeds in Stroke Study]). We rated markers of SVD on baseline brain magnetic resonance imaging: basal ganglia perivascular spaces (number ≥11); cerebral microbleeds (number ≥1); lacunes (number ≥1); and white matter hyperintensities (periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2). We investigated the associations of SVD presence (defined as presence of ≥1 SVD marker) and severity (composite SVD score) with the risk of ischemic stroke during follow-up using a Cox proportional hazards model adjusted for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65–74, female score. Results: We included 1419 patients (mean age: 75.8 years [SD, 10.4]; 42.1% female). The ischemic stroke rate during follow-up in patients with any SVD was 2.20 per 100-patient years (95% CI, 1.60–3.02), compared with 0.98 per 100 patient-years (95% CI, 0.59–1.62) in those without SVD ( P =0.008). After adjusting for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65–74, female score, SVD presence remained significantly associated with ischemic stroke during follow-up (hazard ratio, 1.89 [95% CI, 1.01–3.53]; P =0.046); the risk of recurrent ischemic stroke increased with SVD score (hazard ratio per point increase, 1.33 [95% CI, 1.04–1.70]; P =0.023). Conclusions: In patients anticoagulated for atrial fibrillation after ischemic stroke or transient ischemic attack, magnetic resonance imaging markers of SVD are associated with an increased risk of ischemic stroke during follow-up; improved stroke prevention treatments are required in this population. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02513316.
Published: 2021
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5. Cognitive Impairment Before Atrial Fibrillation-Related Ischemic Events:Neuroimaging and Prognostic Associations

Author: Gargi Banerjee, Edgar Chan, Gareth Ambler, Duncan Wilson, Lisa Cipolotti, Clare Shakeshaft, Hannah Cohen, Tarek Yousry, Rustam Al‐Shahi Salman, Gregory Y. H. Lip, Keith W. Muir, Martin M. Brown, Hans Rolf Jäger, David J. Werring, Louise Shaw, Kirsty Harkness, Jane Sword, Azlisham Mohd Nor, Pankaj Sharma, Deborah Kelly, Frances Harrington, Marc Randall, Matthew Smith, Karim Mahawish, Abduelbaset Elmarim, Bernard Esisi, Claire Cullen, Arumug Nallasivam, Christopher Price, Adrian Barry, Christine Roffe, John Coyle, Ahamad Hassan, Caroline Lovelock, Jonathan Birns, David Cohen, L. Sekaran, Adrian Parry‐Jones, Anthea Parry, David Hargroves, Harald Proschel, Prabel Datta, Khaled Darawil, Aravindakshan Manoj, Mathew Burn, Chris Patterson, Elio Giallombardo, Nigel Smyth, Syed Mansoor, Ijaz Anwar, Rachel Marsh, Sissi Ispoglou, Dinesh Chadha, Mathuri Prabhakaran, Sanjeevikumar Meenakishundaram, Janice O'Connell, Jon Scott, Vinodh Krishnamurthy, Prasanna Aghoram, Michael McCormick, Paul O'Mahony, Martin Cooper, Lillian Choy, Peter Wilkinson, Simon Leach, Sarah Caine, Ilse Burger, Gunaratam Gunathilagan, Paul Guyler, Hedley Emsley, Michelle Davis, Dulka Manawadu, Kath Pasco, Maam Mamun, Robert Luder, Mahmud Sajid, James Okwera, Julie Staals, Elizabeth Warburton, Kari Saastamoinen, Timothy England, Janet Putterill, Enrico Flossman, Michael Power, Krishna Dani, David Mangion, Appu Suman, John Corrigan, Enas Lawrence, and Djamil Vahidassr
Subjects: medicine.medical_specialty, Neuroimaging, Neuropsychological Tests, Brain ischemia, Disability Evaluation, Cognition, Leukoencephalopathies, Predictive Value of Tests, Modified Rankin Scale, Internal medicine, Atrial Fibrillation, Prevalence, medicine, Humans, Cognitive Dysfunction, atrial fibrillation, Prospective Studies, Cognitive decline, Vascular dementia, Stroke, Original Research, Ischemic Stroke, cognitive impairment, business.industry, cerebral small vessel disease, Transient Ischemic Attack (TIA), Atrial fibrillation, vascular dementia, Odds ratio, Prognosis, medicine.disease, United Kingdom, Hyperintensity, brain ischemia, Functional Status, Ischemic Attack, Transient, Cerebral Small Vessel Diseases, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: Background It is likely that a proportion of poststroke cognitive impairment is sometimes attributable to unidentified prestroke decline; prestroke cognitive function is also clinically relevant because it is associated with poor functional outcomes, including death. We investigated the radiological and prognostic associations of preexisting cognitive impairment in patients with ischemic stroke or transient ischemic attack associated with atrial fibrillation. Methods and Results We included 1102 patients from the prospective multicenter observational CROMIS ‐2 (Clinical Relevance of Microbleeds in Stroke 2) atrial fibrillation study. Preexisting cognitive impairment was identified using the 16‐item Informant Questionnaire for Cognitive Decline in the Elderly. Functional outcome was measured using the modified Rankin scale. Preexisting cognitive impairment was common (n=271; 24.6%). The presence of lacunes (odds ratio [OR], 1.50; 95% CI , 1.03–1.05; P =0.034), increasing periventricular white matter hyperintensity grade (per grade increase, OR , 1.38; 95% CI , 1.17–1.63; P OR , 1.26; 95% CI , 1.05–1.51; P =0.011), and medial temporal atrophy grade (per grade increase, OR , 1.61; 95% CI , 1.34–1.95; P mRS >2; adjusted OR , 2.43; 95% CI , 1.42–4.20; P =0.001). Conclusions Preexisting cognitive impairment in patients with atrial fibrillation–associated ischemic stroke or transient ischemic attack is common, and associated with imaging markers of cerebral small vessel disease and neurodegeneration, as well as with longer‐term functional outcome. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02513316.
Published: 2020
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6. 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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7. 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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8. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS) : a pragmatic, double-blind, randomised, controlled trial

Author: Martin Dennis, Gillian Mead, John Forbes, Catriona Graham, Maree Hackett, Graeme J Hankey, Allan House, Stephanie Lewis, Erik Lundström, Peter Sandercock, Karen Innes, Carol Williams, Jonathan Drever, Aileen Mcgrath, Ann Deary, Ruth Fraser, Rosemary Anderson, Pauli Walker, David Perry, Connor Mcgill, David Buchanan, Yvonne Chun, Lynn Dinsmore, Emma Maschauer, Amanda Barugh, Shadia Mikhail, Gordon Blair, Ingrid Hoeritzauer, Maggie Scott, Greig Fraser, Katherine Lawrence, Alison Shaw, Judith Williamson, David Burgess, Malcolm Macleod, Dan Morales, Frank Sullivan, Marian Brady, Ray French, Frederike Van Wijck, Caroline Watkins, Fiona Proudfoot, Joanna Skwarski, Diane Mcgowan, Rachael Murphy, Seona Burgess, William Rutherford, Katrina Mccormick, Ruaridh Buchan, Allan Macraild, Ruth Paulton, Adnan Fazal, Pat Taylor, Ruwan Parakramawansha, Neil Hunter, Jack Perry, John Bamford, Dean Waugh, Emelda Veraque, Caroline Bedford, Mary Kambafwile, Luis Idrovo, Linetty Makawa, Paula Smalley, Marc Randall, Tharani Thirugnana-Chandran, Ahamad Hassan, Richard Vowden, Joanne Jackson, Ajay Bhalla, Anthony Rudd, Chi Kai Tam, Jonathan Birns, Charlotte Gibbs, Leonie Lee Carbon, Elizabeth Cattermole, Katherine Marks, Angela Cape, Lisa Hurley, Sagal Kullane, Nigel Smyth, Charlotte Eglinton, Jennifer Wilson, Elio Giallombardo, Angela Frith, Paul Reidy, Matthew Pitt, Lucy Sykes, Deborah Dellafera, Victoria Croome, Lauriane Kerwood, Mirea Hancevic, Christina Narh, Carley Merritt, John Duffy, Duncan Cooke, Juliet Willson, Ali Ali, Aaizza Naqvi, Christine Kamara, Helen Bowler, Simon Bell, Tracy Jackson, Kirsty Harkness, Kathy Stocks, Suzanna Duty, Clare Doyle, Geoffrey Dunn, Keith Endean, Fiona Claydon, Emma Richards, Jo Howe, Ralf Lindert, Arshad Majid, Katy Dakin, Ahmad Maatouk, Luke Barron, Madana Meegada, Pratap Rana, Anand Nair, Christine Brighouse-Johnson, Jill Greig, Myint Kyu, Sanjeev Prasad, Matthew Robinson, Irfan Alam, Belinda Mclean, Lindsay Greenhalgh, Zenab Ahmed, Christine Roffe, Susan Brammer, Carole Beardmore, Kay Finney, Adrian Barry, Paul Hollinshead, Jeanette Grocott, Holly Maguire, Indira Natarajan, Jayan Chembala, Ranjan Sanyal, Sue Lijko, Nenette Abano, Alda Remegoso, Phillip Ferdinand, Stephanie Stevens, Resti Varquez, Chelsea Causley, Adrian Butler, Philip Whitmore, Caroline Stephen, Racquel Carpio, Joanne Hiden, Girish Muddegowda, Hayley Denic, Jane Sword, Ross Curwen, Martin James, Paul Mudd, Fiona Hall, Julie Cageao, Samantha Keenan, Caroline Roughan, Hayley Kingwell, Anthony Hemsley, Christoph Lohan, Sue Davenport, Angela Bowring, Tamika Chapter, Max Hough, David Strain, Karin Gupwell, Keniesha Miller, Anita Goff, Ellie Cusack, Shirley Todd, Rebecca Partridge, Georgiana Jennings, Kevin Thorpe, Jacquelyn Stephenson, Kelly Littlewood, Mark Barber, Fiona Brodie, Steven Marshall, Derek Esson, Irene Coburn, Caroline Mcinnes, Fiona Ross, Emma Bowie, Heather Barcroft, Victoria Withers, Laura Miller, Paul Willcoxson, Michelle Donninson, Richard Evans, Di Daniel, John Coyle, Michael Keeling, Peter Wanklyn, Mark Elliott, John Wightman, Elizabeth Iveson, Natasha Dyer, Anne-Marie Porteous, Monica Haritakis, Mandy Ward, Lucy Doughty, Lisa Carr, Mark O Neill, Cosmas Anazodo, Paul Wood, Poppy Cottrell, Cheryl Donne, Romina Rodriguez, Ruhail Mir, Jax Westmoreland, Judith Bell, Christopher Emms, Lorraine Wright, Pearl Clark Brown, Elizabeth Bamford, Andrew Stanners, Mike Carpenter, Prabal Datta, Richard Davey, Ann Needle, Marjorie Jane Eastwood, Fathima Zeena Razik, Imran Ghouri, Gavin Bateman, Judy Archer, Venkatesh Balasubramanian, Richard Bowers, Julie Ball, Louise Benton, Linda Jackson, Julie Ellam, Kate Norton, Paul Guyler, Terry Dowling, Sharon Tysoe, Paula Harman, Ashish Kundu, Ololade Omodunbi, Thayalini Loganathan, Stuart Chandler, Shanas Noor, Anwer Siddiqui, Amber Siddiqui, Swapna Kunhunny, Devesh Sinha, Martin Sheppard, Sindhu Rashmi, Elena France, Rajalakshmi Orath Prabakaran, Laura Wilson, Amiirah Ropun, Shyam Kelavkar, Kheng Xiong Ng, Lucy Kamuriwo, Sweni Shah, David Mangion, Camen Constantin, Luigi De Michele Hock, Anne Hardwick, Jayne Borley, Skarlet Markova, Kimberley Netherton, Tara Lawrence, Jo Fletcher, Rebecca Spencer, Helen Palmer, Claire Cullen, Dolores Hamill, Ramesh Durairaj, Zoe Mellor, Tanya Fluskey, Diane Wood, Alison Keeling, Victoria Hankin, Jennifer Peters, Daniela Shackcloth, Thant Hlaing, Rebecca Tangney, Jordan Ewing, Melanie Harrison, Sarah Stevenson, Victoria Sutton, Mohamed Soliman, Julia Hindle, Elizabeth Watson, Claire Hewitt, Susie Butler, Ibrahim Wahishi, Sarwat Arif, Amy Fields, Jagdish Sharma, Rose Brown, Caroline Taylor, Sarah Bell, Simon Leach, Chris Patterson, Sophia Khan, Helen Wilson, Joanne Price, Hawraman Ramadan, Stuart Maguire, Ruth Bellfield, Michaela Hooley, Umair Hamid, Waqar Gaba, Robina Ghulam, Leslie Masters, Outi Quinn, Lakshmanan Sekaran, Margaret Tate, Niaz Mohammed, Kiranjit Bharaj, Frances Justin, Rajan Pattni, Lanka Alwis, Sakthivel Sethuraman, Rianne 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Abigail Hynes, Emma Nurse, Syed Abid Raza, Sarah Jones, Udaya Pallikona, Bleddyn Edwards, Geraint Morgan, Kirsty Dennett, Helen Tench, Ronda Loosley, Toby Trugeon-Smith, Rhian Jones, Richard Williams, Donna Robson, Sunanda Mavinamane, Sanjeevi Meenakshisundaram, Lalitha Ranga, Sharon Dealing, Andrew Hill, Margaret Hargreaves, Tom Smith, Julie Bate, Linda Harrison, Ramanathan Kirthivasan, Emma Cannon, Joanne Topliffe, Rebecca Keskeys, Sarah Williams, Fiona Mcneela, Frances Cairns, Thomas James, Amanda Lyle, Sheela Shah, George Zachariah, Lauren Fergey, Susan Smolen, Lucy Cooper, Elizabeth Bohannan, Siddiq Omer, Sageet Amlani, Nadia Hunter, Melissa Hawkes-Blackburn, Giosue Gulli, Alice Peacocke, Justine Amero, Maria Burova, Ottilia Speirs, Steph Levy, Lynda Francis, Susan Holland, Sean Brotheridge, Helen Lyon, Christine Hare, Samantha Jackson, Lorraine Stephenson, Samer Al Hussayni, James Featherstone, Agness Bwalya, Arun Singh, M N Goorah, Jamie Walford, Angela Bell, Christine Kelly, Darren Rusk, Deborah Sutton, Farzana Patel, Stephen Duberley, Kathryn Hayes, Lorraine Hunt, Ahmed El Nour, Sacha Honour, Chloe Box, Simon Dyer, Lynne Brown, Kerry Elliott, Emma Temlett, John Paterson, Rosie Furness, Shelli Young, Enoch Orugun, Chris Brewer, Sarah Thornthwaite, Hannah Crowther, Rachel Glover, Moe Sein, Kashif Haque, Elspeth Gibson, Sam Wong, Karen Rotchell, Karen Burton, Lisa Brookes, Linda Bailey, Chris Lindley, Abbi Murray, Karen Waltho, Maureen Holland, Pradeep Kumar, Purnima Harlekar, Laura Booth, Charlotte Culmsee, Jade Drew, Mohammad Khan, Nicola Mackenzie, Carmel Thomas, Jane Ritchie, James Barker, Michael Haley, Donna Cotterill, Lynne Lane, Christine Little, Dawn Simmons, Glenn Saunders, Harvey Dymond, Sarah Kidd, Rachel Warinton, Yara Neves-Silva, Branimir Nevajda, Michael Villaruel, Udayaraj Umasankar, Seema Patel, Anna Man, Natasha Christmas, Ravi Rangasamy, Richard Ladner, Georgina Butt, Wilson Alvares, Narasimha Gadi, Michael Power, Belinda Wroath, Kevin Dynan, David Wilson, Sarah Crothers, Catherine Leonard, Samantha Hagan, Geraldine Douris, Djamil Vahidassr, Alastair Thompson, Brian Gallen, Shirley Mckenna, Collette Edwards, Clare Mcgoldrick, Murdi Bhattad, Khalil Kawafi, Deborah Morse, Patricia Jacob, Lisa Turner, Narayanamoorti Saravanan, Linda Johnson, Sadie Humphrey, Robert Namushi, Ramesh Patel, Jemma Mclaughlin, Paul Omahony, Esther Osikominu, Chukwuka Orefo, Chisha Mcdonald, Esther Makanju, Tabindah Khan, Grace Appiatse, Helena Stone, Martia Augustin, Alicia Wardale, Maqsud Salehin, Duncan Bailey, Luciano Garcia-Alen, Latheef Kalathil, Sarah Tinsley, Taya Jones, Kelly Amor, Andrew Ritchings, Emma Margerum, Jane Horton, Richard Miller, Nireekshana Gautam, Julie Meir, Amaryl Jones, Janet Putteril, Mirella Lepore, Rachel Gallifent, Laura-Louise Arundell, Catherine Mcredmond, Alicia Goulding, Vivek Nadarajan, Julia Laurence, Su Fung Lo, Sabina Melander, Paul Nicholas, Elizabeth Woodford, Gillian Mckenzie, Vietland Le, Jacolene Crause, Robert Luder, Maneesh Bhargava, Girish Bhome, Venetia V Johnson, Dara Chesser, Hayley Bridger, Elodie Murali, Jon Scott, Susan Morrison, Amy Burns, Julie Graham, Madeline Duffy, Khalid Ali, Emma Pitcher, Jane Gaylard, Julie Newman, Sunil Punnoose, Sarah Besley, Kirtan Purohit, Amy Rees, Mark Davy, Osman Chohan, Muhammad Fozan Khan, Rachel Walker, Vicky Murray, Charlotte Bent, Susan Oakley, Cassilda Peixoto, Suzanne Jones, Gaybrielle Livingstone, Fiona Butler, Sally Bradfield, Laura Gordon, Jenneke Schmit, Anika Wijewardane, Tineke Edmunds, Rebecca Wills, Catherine Medcalf, Lucia Argandona, Larissa Cuenoud, Hanna Hassan, Esther Erumere, Aidan Ocallaghan, Patrick Gompertz, Ozlem Redjep, Grace Auld, Anna Song, Tillana Tarkas, Hashim Kabash, Rumbi Hungwe, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Population and Behavioural Science Division, and University of St Andrews. School of Medicine
Subjects: RM, medicine.medical_specialty, Neurology, Neurologi, NDAS, 030204 cardiovascular system & hematology, Placebo, Minimisation (clinical trials), Article, B700, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, Modified Rankin Scale, law, Fluoxetine, Internal medicine, Humans, Medicine, 030212 general & internal medicine, R2C, Acute stroke, business.industry, ~DC~, General Medicine, Odds ratio, RM Therapeutics. Pharmacology, Stroke, RC Internal medicine, BDC, business, Selective Serotonin Reuptake Inhibitors, RC, medicine.drug
Abstract: Background: Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.Methods: FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.Findings: Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.Interpretation: Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.Funding: UK Stroke Association and NIHR Health Technology Assessment Programme.
Published: 2019
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9. Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Author: Ruth Graham, Charlotte Eglinton, Swapna Kunhunny, J Banns, Alison K Wright, Sunil Munshi, C Khuoge, Beverley McClelland, A Benford, Jean Buxton, Maia Beridze, K Deighton, Neha Chopra, Nichola Motherwell, Emily C. O'Brien, Sonia S. Anand, Anand Dixit, Una Poultney, N Beridze, Jessica Beavan, K Dizayee, Thompson G. Robinson, Deborah Howcroft, Alison Sarah rachel Mcloughlin, A Kenton, Derek Esson, A Tittle, L Matter, Kerstin Knops, C Hubbuck, Kath Chapman, R Rangasamay, Ranjan Sanyal, Sarah Lewis, Alpha Anthony, Sarah Board, Janice Irvine, Anna Verrion, Katherine Whittamore, N Khizanishvili, L O'Shea, Lisa Shaw, K Ayes, Tracey Dobson, N Akiashvili, Gill Rogers, Jenny Peters, Alda Remegoso, S S Hansen, James A. White, T Attygalle, Rosalind Brown, Irene Martin, Manesh R. Patel, D O'Kane, Stuart J. Pocock, Khalid Rashed, G Spurling, Sharon Tysoe, Frances Harrington, Margo Henry, Rowilson Jarapa, Julia Hindle, K A Kay, Carinna Vickers, S Duty, Angela Bowring, David Eveson, Saul Sundayi, Mary Kambafwile, Rashmi Kumar, Jack Roffe, Marilyn James, Natalie Temple, R Oliver, Christine Kelly, M Niemierko, J Chembala, S Jones, M Dent, K Chatterjee, S Atkinson, J Tomlinson, S Norman, E Cattermole, P Daboo, Nicola Gilzeane, Anne Hardwick, Pietro Cariga, C Rankin, David A. Wood, Lelia Duley, John Bamford, L Holford, J Good, C Ambulo, S Gomm, Girish Muddegowda, Fiona Wright, M Alao, L Sztriha, Maite D. Rodriguez, Christine Dickson, S Merotra, Helen Bearne, Ann Needle, Emma Mckenzie, Olga Balazikova, Emily Osborne, A Lankester, Rod S Taylor, Pauline Fitzell, Bernard Esisi, E Young, Richard Donnelly, Anu Joyson, Debbie Morgan, Fran Watson, Caroline Mcinnes, C Padilla-Harris, Stephanie McCann, T Ajao, Suzanne Lucas, Inez Wynter, Barbara Longland, Don Sims, Gavin Bateman, Anthony Hemsley, Vera Cvoro, Fiona Kennedy, Peter Langhorne, Adrian Butler, P Jacob, Barry Moynihan, Amit K. Mistri, W Sunman, Hannah Beadle, Polly Scutt, M Garside, Glyn Fletcher, Deborah Walstow, L Ryan, Michelle Fawcett, D Wilkinson, E Gibson, O Orugun, Malcolm R. Macleod, Philip M.W. Bath, Elio Giallombardo, T Kherkheulidze, Lourda Kerin, Clare Doyle, Brigid Hairsine, N Kakabadze, B Wadams, Enas Lawrence, Dinesh Chadha, I Memon, Cheryl L. Perkins, Victoria Sutton, C.B. Patel, A Ravindrane, K Javaid, Mahmud Sajid, T Tsanava, Y Duodu, Timothy J. England, Geoffrey A. Rose, Sheila Nyabadza, Louisa M. Christensen, M Bajoriene, F Faola, J Kok, C Vernon, Aravindakshan Manoj, E Horsley, T Gordon, Linda Cowie, S Hurdowar, D Sandler, Temi Adedoyin, Mandy Couser, C Jenkins, C Pringle, Paula Lopez, Vicky Taylor, James Cunningham, Gillian Courtauld, S Maheswaran, H Rehman, Christine Roffe, M Sein, Carla Richardson, John B. Davis, Nenette Abano, Racquel Carpio, Sheila Mashate, P Christian, Lynn Dixon, Dulka Manawadu, Jeanette Grocott, Peter Owusu-Agyei, P Farren, F K Chan, Komal Ali, Annemarei Ranta, Judith Clarke, Dean Waugh, Stan Heptinstall, M Reader, Nikola Sprigg, John F. Corrigan, Caroline Roughan, F Brodie, Paula Harman, P Webster, Kenneth Smith, Julie Reddan, Angela Willberry, Peter Howard, Kay Finney, S Buddha, C Hewitt, M Zaidi, Tracy Marsden, Heather Gow, Robert A. Dineen, Kimberley Netherton, Kashif Musarrat, Emma Barbon, V Riddell, G Storey, Ahamad Hassan, O Adegbaju, S Wong, Bethan Charles, Bindu Gregary, Rhys Williams, M G Metiu, Nilofer Dayal, C Lawlor, Kirsten E Anderson, R Icart Palau, N Khanom, C Stevenson, Prabel Datta, Betty Mokoena, Kelly Chan, Amanda Hedstrom, Sonia Raj, Y Gruenbeck, D Dellafera, Georgina Butt, A Peacocke, James Okwera, L Mokoena, Holly Maguire, Mohana Maddula, C Bailey, Ian Shread, LáShauntá M. Glover, Elizabeth Keeling, Mari Smith, Jane Powell, A Tevdoradze, Christopher Price, Hannah Rudenko, K Gill, Laura Howaniec, P Lingwood, Katherine Marks, Ivan Iniesta, F Barrett, Barbara Madigan, Emery N. Brown, Katie Flaherty, Gail Hann, Mark Barber, Kelley Storey, Aparna Pusalkar, Jason P. Appleton, Joanne Hiden, R Jolly, Hedley C. A. Emsley, J Chambers, Christina Kruuse, Mairead Osborn, P Lai, Tracy Fuller, David G. Bruce, Robert Namushi, Martin Cooper, Peter Murphy, Naomi Jeyaraj, Hayley Kingwell, A Nair, Robert S.M. Davies, Katrina McCormick, Rachel L. Lakey, Sharon Dealing, F Leslie, Peter Wilkinson, Amitava Banerjee, Penelope Cox, Janice E. O’Connell, N Sikondari, Sandra Leason, Lisa J Woodhouse, Judith Bell, Puneet Dangri, Donna Butler, Judith Dube, Rachel Gascoyne, Amberly Brigden, Debs Kelly, Renuka Erande, Kirsty Harkness, Sarah Trippier, Kirsten Harvey, Georgina Ayres, R Rowland-Axe, E Campbell, Sue Lyjko, Sylvia Szabo, David Mangion, Suzanne Ragab, C Hilaire, Alan A Montgomery, Dawn Tomlin, John Paterson, K Muhidden, Grace Auld, C Keaveney, Hannah Crowther, Lisa Hyatt, Louise E. Jackson, K Castro, Khaled Elfandi, H Russell, S Tennant, Ozlem Redjep, Tim Cassidy, Linda Y Johnson, Amulya Misra, E Khoromana, Catherine Ovington, Stuart Maguire, S Khan, Zoe Mellor, Michael Funnell, Hugh S. Markus, Emma Richards, I Toidze, Colin Smith, R Sivakumar, Janet Wilson, Amina Ahmed, A Mohd Nor, A Barkat, Line Bentsen, K Whysall, Carol L Clarke, N Sengupta, Meena Srinivasan, Balakrishna Kumar, Mgg Soliman, A Thomson, Adrian Barry, Abul Azim, Ed Gamble, H Eccleson, Kelly Marie Shaw, Christine Schofield, Linetty Makawa, Carole Hays, David Hargroves, Jordi Margalef, S Butler, H Webb, Carol Denniss, Samantha Stafford, Faye Shelton, D Forrest, Amanda Buck, Tarn Nozedar, Indira Natarajan, Jane Perez, Susanna R. Stevens, Denise Button, Mary Johnes, Samantha Keenan, Olivia C. Geraghty, Eva Beranova, Emma Jinks, S Hassan, Caroline McGhee, Nicola Persad, Gunaratnam Gunathilagan, Clare Buckley, Jennifer Mitchell, Mike Clarke, Mathew Burn, B Bhaskaran, D Hayward, Lucy Belle Guthrie, S Meenakshisundaram, Anushka Warusevitane, O Speirs, J O'Callaghan, Sudipto Ghosh, Peter Wilding, Helen Cochrane, Susan Clayton, Mandy Doherty, Fiona Price, L Montague, Valerie Hogg, S Arif, Beth Hazel, Margaret Ball, S Johnson-Holland, S Booth, N Rands, Dionne Hove, Teresa Thompson, C Krarup Hansen, Lisa Manning, Andrew Smith, Jo Howe, Jill Greig, Kailash Krishnan, Caroline Watchurst, L Finlay, Sandra Nelson, Toby Black, S Tilby, Zin Naing, D Morse, David Broughton, K Preece, M Platton, M Siddiqui, Angela Dodd, Catrin Blank, Maria Bokhari, Jacqueline Furnace, F Hammonds, Helen Guy, A Lehman, J Hunt, S Windebank, Becky Jupp, K Fotherby, Ruth Bellfield, P Wanklyn, D Hilton, Amy Steele, S Mahmood, N Lobjanidze, Sarah Finlay, L Hunt, M Krasinska-Chavez, Gemma Grimwood, H H Jensen, J. Duignan, Jane Gaylard, Asaipillai Asokanathan, Joanna O'Reilly, J Kessell, Diane Havard, T Fluskey, L Lee-Carbon, Graham Venables, Margi Godfrey, L Boxall, C Douglass, Emelda Veraque, Elaine Amis, M Chowdhury, Rekha Keshvara, Adrian Blight, G Thomas, Marc Randall, S Stoddart, Paul Guyler, Rita Ghatala, Janet T Scott, Kathy J. Jenkins, Sarah Ross, John Aeron-Thomas, C Allcock, J Goodsell, Ifan Jones, D Kakabadze, T T Thomsen, V Petrovic, I. Watson, C Athulathmudali, Hanne Christensen, Susan Crawford, Christine Kamara, James McIlmoyle, Stephen Woodward, Christine McAlpine, Emma Temlett, Gwendoline Wilkes, Benjamin Hyams, L Mills, S Brixey, Raj Shekhar, P Findlay, Markus, Hugh [0000-0002-9794-5996], and Apollo - University of Cambridge Repository
Subjects: Male, medicine.medical_specialty, Georgia, Ticlopidine, Denmark, Hemorrhage, 030204 cardiovascular system & hematology, Risk Assessment, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Ischemia, Recurrence, Modified Rankin Scale, Internal medicine, medicine, Humans, Thrombolytic Therapy, Prospective Studies, cardiovascular diseases, Stroke, Aged, Aspirin, business.industry, Dipyridamole, General Medicine, Guideline, Middle Aged, Clopidogrel, medicine.disease, United Kingdom, Treatment Outcome, Ischemic Attack, Transient, Research Design, Acute Disease, Platelet aggregation inhibitor, Drug Therapy, Combination, Female, business, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery, New Zealand, medicine.drug
Abstract: Summary Background Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p Interpretation Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice. Funding National Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.
Published: 2017

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1. Potential missed opportunities to prevent ischaemic stroke: prospective multicentre cohort study of atrial fibrillation-associated ischaemic stroke and TIA

2. Practical '1-2-3-4-Day' Rule for Starting Direct Oral Anticoagulants After Ischemic Stroke With Atrial Fibrillation: Combined Hospital-Based Cohort Study

3. Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

4. Small Vessel Disease and Ischemic Stroke Risk During Anticoagulation for Atrial Fibrillation After Cerebral Ischemia

5. Cognitive Impairment Before Atrial Fibrillation-Related Ischemic Events:Neuroimaging and Prognostic Associations

6. 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

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

8. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS) : a pragmatic, double-blind, randomised, controlled trial

9. Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

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