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1. 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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2. Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention

Author

Panagiotis Halvatsiotis, Giuseppe Reale, Jennifer A. Frontera, Giuseppe Martini, S. Pegoraro, Leonardo Pantoni, Aristeidis H. Katsanos, Piergiorgio Lochner, Daniel Strbian, Giorgia Zepponi, Valentina Saia, Karen L. Furie, Giancarlo Agnelli, Elisa Giorli, Erica Scher, Lina Palaiodimou, Valentina Arnao, Giorgio Silvestrelli, Simona Marcheselli, Letizia Riva, Andrea Zini, Angela Risitano, Tiziana Tassinari, Carlo Emanuele Saggese, Francesco Palmerini, Erika Schirinzi, Michael E. Reznik, Marina Mannino, Jukka Putaala, Maria Kosmidou, Michela Giustozzi, Cesare Porta, Maurizio Paciaroni, Marina Padroni, Loris Poli, Maria Cristina Vedovati, Danilo Toni, Manuel Cappellari, Alessandro Rocco, Alessandro Pezzini, Ashkan Shoamanesh, Stefano Forlivesi, Serena Monaco, Raffaele Ornello, Simona Sacco, Silvia Rosa, Shadi Yaghi, Valeria Terruso, Andrea Alberti, Francesco Corea, Elena Ferrari, Christoph Stretz, Marialuisa Zedde, Monica Acciarresi, Cataldo D'Amore, Kateryna Antonenko, Nemanja Popovic, Francesca Guideri, Evangelos Ntais, Boris Doronin, Luca Masotti, Filippo Angelini, Giovanni Orlandi, Licia Denti, Nicola Mumoli, Sotirios Giannopoulos, Elisabetta Toso, Maria Giulia Mosconi, Paolo Aridon, Aurelia Zauli, Giuseppe Micieli, Azmil H. Abdul-Rahim, Laura Brancaleoni, Marina Diomedi, Elisa Grifoni, Georgios Tsivgoulis, Maurizio Acampa, Michele Venti, Walter Ageno, Pietro Caliandro, Alfonso Ciccone, Isabella Canavero, Laura Franco, George Ntaios, Fabio Bandini, Vera Volodina, Pierluigi Bertora, Dimitrios Sagris, Antonio Baldi, Michele Romoli, Hanne Sallinen, Michelangelo Mancuso, Yuriy Flomin, Rossana Tassi, Valeria Caso, Massimo Del Sette, Enrico Maria Lotti, Antonio Gasparro, Alberto Chiti, Jesse Dawson, Brian Mac Grory, Alberto Rigatelli, Paciaroni, Maurizio, Agnelli, Giancarlo, Giustozzi, Michela, Caso, Valeria, Toso, Elisabetta, Angelini, Filippo, Canavero, Isabella, Micieli, Giuseppe, Antonenko, Kateryna, Rocco, Alessandro, Diomedi, Marina, Katsanos, Aristeidis H, Shoamanesh, Ashkan, Giannopoulos, Sotirio, Ageno, Walter, Pegoraro, Samuela, Putaala, Jukka, Strbian, Daniel, Sallinen, Hanne, Mac Grory, Brian C, Furie, Karen L, Stretz, Christoph, Reznik, Michael E, Alberti, Andrea, Venti, Michele, Mosconi, Maria Giulia, Vedovati, Maria Cristina, Franco, Laura, Zepponi, Giorgia, Romoli, Michele, Zini, Andrea, Brancaleoni, Laura, Riva, Letizia, Silvestrelli, Giorgio, Ciccone, Alfonso, Zedde, Maria Luisa, Giorli, Elisa, Kosmidou, Maria, Ntais, Evangelo, Palaiodimou, Lina, Halvatsiotis, Panagioti, Tassinari, Tiziana, Saia, Valentina, Ornello, Raffaele, Sacco, Simona, Bandini, Fabio, Mancuso, Michelangelo, Orlandi, Giovanni, Ferrari, Elena, Pezzini, Alessandro, Poli, Lori, Cappellari, Manuel, Forlivesi, Stefano, Rigatelli, Alberto, Yaghi, Shadi, Scher, Erica, Frontera, Jennifer A, Masotti, Luca, Grifoni, Elisa, Caliandro, Pietro, Zauli, Aurelia, Reale, Giuseppe, Marcheselli, Simona, Gasparro, Antonio, Terruso, Valeria, Arnao, Valentina, Aridon, Paolo, Abdul-Rahim, Azmil H, Dawson, Jesse, Saggese, Carlo Emanuele, Palmerini, Francesco, Doronin, Bori, Volodina, Vera, Toni, Danilo, Risitano, Angela, Schirinzi, Erika, Del Sette, Massimo, Lochner, Piergiorgio, Monaco, Serena, Mannino, Marina, Tassi, Rossana, Guideri, Francesca, Acampa, Maurizio, Martini, Giuseppe, Lotti, Enrico Maria, Padroni, Marina, Pantoni, Leonardo, Rosa, Silvia, Bertora, Pierluigi, Ntaios, George, Sagris, Dimitrio, Baldi, Antonio, D'Amore, Cataldo, Mumoli, Nicola, Porta, Cesare, Denti, Licia, Chiti, Alberto, Corea, Francesco, Acciarresi, Monica, Flomin, Yuriy, Popovic, Nemanja, and Tsivgoulis, Georgios

Subjects
Male, Administration, Oral, 030204 cardiovascular system & hematology, Settore MED/11, 0302 clinical medicine, 80 and over, risk factors, Medicine, atrial fibrillation, Prospective Studies, Aged, 80 and over, cerebral hemorrhage, logistic models, white matter, Aged, Antithrombins, Atrial Fibrillation, Case-Control Studies, Cerebral Hemorrhage, Female, Humans, Middle Aged, Risk Factors, Stroke, Atrial fibrillation, Vitamin K antagonist, 3. Good health, Administration, Settore MED/26 - Neurologia, Cardiology and Cardiovascular Medicine, medicine.drug, Oral, medicine.medical_specialty, medicine.drug_class, Settore MED/26, Lower risk, 03 medical and health sciences, Internal medicine, cardiovascular diseases, logistic model, Advanced and Specialized Nursing, Intracerebral hemorrhage, business.industry, Warfarin, medicine.disease, Clinical trial, Concomitant, Heart failure, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.

Published
2021
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3. Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes

Author

Michele Venti, Walter Ageno, Alfonso Ciccone, Luana Gentile, Vanessa Gourbali, Antonio Baldi, Elisa Grifoni, László Csiba, Cataldo D'Amore, Prasanna Tadi, Yuriy Flomin, Rossana Tassi, Sung Il Sohn, Bruno Bonetti, Patrik Michel, Erika Schirinzi, Alessandro Padovani, Cindy Tiseo, Maria Luisa De Lodovici, Odysseas Kargiotis, Konstantinos Vadikolias, Shadi Yaghi, Maurizio Paciaroni, Georgios Tsivgoulis, Enrico Maria Lotti, Manuel Cappellari, Lilla Szabó, Ashraf Eskandari, Federica Letteri, Leonardo Ulivi, Chrissoula Liantinioti, Valeria Caso, Lina Palaiodimou, Dirk Deleu, Jesse Dawson, Licia Denti, Konstantinos Makaritsis, Gianni Lorenzini, Marina Mannino, Monica Acciarresi, Miriam Maccarrone, Nicola Mumoli, Marta Bellesini, Simona Sacco, George Athanasakis, Umberto Scoditti, Maurizio Acampa, Giuseppe Martini, Brian Mac Grory, Alberto Rigatelli, Kristian Barlinn, Vieri Vannucchi, Serena Monaco, Efstathia Karagkiozi, Elisa Giorli, Francesca Guideri, Martina Giuntini, Dorjan Zabzuni, Davide Imberti, Giorgio Silvestrelli, Luca Masotti, Loris Poli, Karen L. Furie, Alessio Pieroni, Marialuisa Zedde, Franco Galati, Andrea Alberti, Giancarlo Agnelli, Jessica Barlinn, Turgut Tatlisumak, Maria Chiara Caselli, Boris Doronin, Liisa Tomppo, Kennedy R. Lees, Mario Maimone Baronello, Maria Giulia Mosconi, Jukka Putaala, Tiziana Tassinari, Azmil H. Abdul-Rahim, Peter Vanacker, Christina Rueckert, Valentina Bogini, Alessandro Pezzini, Francesco Corea, Giovanni Orlandi, Simona Marcheselli, Michela Giustozzi, Theodore Karapanayiotides, Michelangelo Mancuso, George Ntaios, Fabio Bandini, Vera Volodina, Nicola Giannini, Cesare Porta, Danilo Toni, Alberto Chiti, and Massimo Del Sette

Subjects
Severe bleeding, medicine.medical_specialty, Stroke recurrence, Infarction, stroke recurrence, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Original Research Articles, Internal medicine, Ischaemic stroke, Acute stroke, Medicine, atrial fibrillation, In patient, Acute ischemic stroke, business.industry, Atrial fibrillation, medicine.disease, Cardiology, Human medicine, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

Introduction The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80). Discussion our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

Published
2020
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4. Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study

Author

Maurizio Paciaroni, Valeria Caso, Giancarlo Agnelli, Maria Giulia Mosconi, Michela Giustozzi, David Julian Seiffge, Stefan T. Engelter, Philippe Lyrer, Alexandros A. Polymeris, Lilian Kriemler, Annaelle Zietz, Jukka Putaala, Daniel Strbian, Liisa Tomppo, Patrik Michel, Davide Strambo, Alexander Salerno, Suzette Remillard, Manuela Buehrer, Odessa Bavaud, Peter Vanacker, Susanna Zuurbier, Laetitia Yperzeele, Caroline M.J. Loos, Manuel Cappellari, Andrea Emiliani, Marialuisa Zedde, Azmil Abdul-Rahim, Jesse Dawson, Robert Cronshaw, Erika Schirinzi, Massimo Del Sette, Christoph Stretz, Narendra Kala, Michael Reznik, Ashley Schomer, Brian Mac Grory, Mahesh Jayaraman, Ryan McTaggart, Shadi Yaghi, Karen L. Furie, Luca Masotti, Elisa Grifoni, Danilo Toni, Angela Risitano, Anne Falcou, Luca Petraglia, Enrico Maria Lotti, Marina Padroni, Lucia Pavolucci, Piergiorgio Lochner, Giorgio Silvestrelli, Alfonso Ciccone, Andrea Alberti, Michele Venti, Laura Traballi, Chiara Urbini, Odysseas Kargiotis, Alessandro Rocco, Marina Diomedi, Simona Marcheselli, Pietro Caliandro, Aurelia Zauli, Giuseppe Reale, Kateryna Antonenko, Eugenia Rota, Tiziana Tassinari, Valentina Saia, Francesco Palmerini, Paolo Aridon, Valentina Arnao, Serena Monaco, Salvatore Cottone, Antonio Baldi, Cataldo D’Amore, Walter Ageno, Samuela Pegoraro, George Ntaios, Dimitrios Sagris, Sotirios Giannopoulos, Maria Kosmidou, Evangelos Ntais, Michele Romoli, Leonardo Pantoni, Silvia Rosa, Pierluigi Bertora, Alberto Chiti, Isabella Canavero, Carlo Emanuele Saggese, Maurizio Plocco, Elisa Giorli, Lina Palaiodimou, Eleni Bakola, Georgios Tsivgoulis, Fabio Bandini, Antonio Gasparro, Valeria Terruso, Marina Mannino, Alessandro Pezzini, Raffaele Ornello, Simona Sacco, Nemanja Popovic, Umberto Scoditti, Antonio Genovese, Licia Denti, Yuriy Flomin, Michelangelo Mancuso, Elena Ferrari, Maria Chiara Caselli, Leonardo Ulivi, Nicola Giannini, Gian Marco De Marchis, Paciaroni, Maurizio, Caso, Valeria, Agnelli, Giancarlo, Mosconi, Maria Giulia, Giustozzi, Michela, Seiffge, David Julian, Engelter, Stefan T, Lyrer, Philippe, Polymeris, Alexandros A, Kriemler, Lilian, Zietz, Annaelle, Putaala, Jukka, Strbian, Daniel, Tomppo, Liisa, Michel, Patrik, Strambo, Davide, Salerno, Alexander, Remillard, Suzette, Buehrer, Manuela, Bavaud, Odessa, Vanacker, Peter, Zuurbier, Susanna, Yperzeele, Laetitia, Loos, Caroline M J, Cappellari, Manuel, Emiliani, Andrea, Zedde, Marialuisa, Abdul-Rahim, Azmil, Dawson, Jesse, Cronshaw, Robert, Schirinzi, Erika, Del Sette, Massimo, Stretz, Christoph, Kala, Narendra, Reznik, Michael, Schomer, Ashley, Grory, Brian Mac, Jayaraman, Mahesh, McTaggart, Ryan, Yaghi, Shadi, Furie, Karen L, Masotti, Luca, Grifoni, Elisa, Toni, Danilo, Risitano, Angela, Falcou, Anne, Petraglia, Luca, Lotti, Enrico Maria, Padroni, Marina, Pavolucci, Lucia, Lochner, Piergiorgio, Silvestrelli, Giorgio, Ciccone, Alfonso, Alberti, Andrea, Venti, Michele, Traballi, Laura, Urbini, Chiara, Kargiotis, Odyssea, Rocco, Alessandro, Diomedi, Marina, Marcheselli, Simona, Caliandro, Pietro, Zauli, Aurelia, Reale, Giuseppe, Antonenko, Kateryna, Rota, Eugenia, Tassinari, Tiziana, Saia, Valentina, Palmerini, Francesco, Aridon, Paolo, Arnao, Valentina, Monaco, Serena, Cottone, Salvatore, Baldi, Antonio, D'Amore, Cataldo, Ageno, Walter, Pegoraro, Samuela, Ntaios, George, Sagris, Dimitrio, Giannopoulos, Sotirio, Kosmidou, Maria, Ntais, Evangelo, Romoli, Michele, Pantoni, Leonardo, Rosa, Silvia, Bertora, Pierluigi, Chiti, Alberto, Canavero, Isabella, Saggese, Carlo Emanuele, Plocco, Maurizio, Giorli, Elisa, Palaiodimou, Lina, Bakola, Eleni, Tsivgoulis, Georgio, Bandini, Fabio, Gasparro, Antonio, Terruso, Valeria, Mannino, Marina, Pezzini, Alessandro, Ornello, Raffaele, Sacco, Simona, Popovic, Nemanja, Scoditti, Umberto, Genovese, Antonio, Denti, Licia, Flomin, Yuriy, Mancuso, Michelangelo, Ferrari, Elena, Caselli, Maria Chiara, Ulivi, Leonardo, Giannini, Nicola, De Marchis, Gian Marco, and Neurology

Subjects
Oral, Advanced and Specialized Nursing, hypertension, recurrence, anticoagulant, Administration, Oral, Anticoagulants, Hemorrhage, Settore MED/26, Brain Ischemia, Stroke, Risk Factors, Administration, Atrial Fibrillation, Humans, Settore MED/26 - Neurologia, Human medicine, Neurology (clinical), Prospective Studies, Cardiology and Cardiovascular Medicine, atrial fibrillation, ischemic stroke, Ischemic Stroke
Abstract

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Published
2022

5. Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention

Author

Panagiotis Papamichalis, Marina Padroni, Katiuscia Nardi, Maria Cristina Vedovati, Erika Schirinzi, Konstantinos Makaritsis, Serena Monaco, Valentina Saia, Karen L. Furie, Giancarlo Agnelli, Kennedy R. Lees, Dirk Deleu, Sotirios Giannopoulos, Azmil H. Abdul-Rahim, Miriam Maccarrone, Tiziana Tassinari, Jukka Putaala, Alexandros A Polymeris, Marina Diomedi, Elena Ferrari, Shadi Yaghi, Alexandra Rimoldi, Monica Acciarresi, Apostolos Komnos, Efstathia Karagkiozi, Elisabetta Toso, Gian Marco De Marchis, Maria Giulia Mosconi, Francesca Guideri, Aristeidis H. Katsanos, Luca Masotti, Piergiorgio Lochner, Angela Risitano, Danilo Toni, Elisa Giorli, Silvia Rosa, Alessandro Pezzini, Francesco Corea, Leonardo Pantoni, Boris Doronin, Filippo Angelini, Giovanni Orlandi, Simona Marcheselli, Chrysoula Liantinioti, Michela Giustozzi, Licia Denti, Manuel Cappellari, Marialuisa Zedde, Cataldo D'Amore, Patrizia Pierini, Elena Pinuccia Verrengia, Kateryna Antonenko, Stefan T. Engelter, Giorgio Silvestrelli, Patrik Michel, Bruno Bonetti, Leonardo Ulivi, Alessandro Rocco, Nicola Mumoli, Lina Palaiodimou, Andrea Alberti, Marina Mannino, Maurizio Paciaroni, Nemanja Popovic, Sung Il Sohn, Marija Zarkov, Odysseas Kargiotis, Ashraf Eskandari, Antonio Baldi, Massimo Del Sette, Michelangelo Mancuso, Michele Venti, Walter Ageno, Alfonso Ciccone, Alberto Chiti, Kalliopi Perlepe, George Ntaios, Silvia Galliazzo, Fabio Bandini, Vera Volodina, Pierluigi Bertora, Nicola Giannini, Georgios Tsivgoulis, Maurizio Acampa, David J. Seiffge, Elisa Grifoni, Brian Mac Grory, Paola Santalucia, Yuriy Flomin, Rossana Tassi, Valeria Caso, Enrico Maria Lotti, and Giuseppe Martini

Subjects
Oral, Male, medicine.medical_specialty, medicine.drug_class, Administration, Oral, 030204 cardiovascular system & hematology, Risk Assessment, Brain Ischemia, Settore MED/11, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Atrial Fibrillation, atrial fibrillation, humans, prevention and control, risk factors, stroke, 80 and over, medicine, Humans, In patient, Stroke, Aged, Aged, 80 and over, Advanced and Specialized Nursing, business.industry, Age Factors, Warfarin, Anticoagulants, Atrial fibrillation, Middle Aged, Vitamin K antagonist, medicine.disease, 3. Good health, Stroke prevention, Administration, Cardiology, Settore MED/26 - Neurologia, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background and Purpose— Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non–vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods— Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results— Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95–5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63–9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83–3.16), and CHA 2 DS 2 -VASc score (OR, 1.72 for each point increase; 95% CI, 1.58–1.88) were associated with ischemic events. Among the CHA 2 DS 2 -VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33–0.61). Conclusions— In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA 2 DS 2 -VASc score were associated with increased risk of cerebrovascular events.

Published
2019
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6. Anticoagulation After Stroke in Patients With Atrial Fibrillation

Author

Francesca Guideri, Martina Giuntini, Luca Masotti, Sung Il Sohn, László Csiba, Marta Bellesini, Ludovica Anna Cimini, Lars-Peder Pallesen, Michele Venti, Walter Ageno, Efstathia Karagkiozi, Davide Imberti, Leonardo Ulivi, Alessandro Padovani, Giancarlo Agnelli, Giovanni Orlandi, Danilo Toni, Gianni Lorenzini, Alfonso Ciccone, Dirk Deleu, Licia Denti, Federica Letteri, Giorgio Bono, Karen L. Furie, Vieri Vannucchi, Miriam Maccarrone, Cecilia Becattini, Theodore Karapanayiotides, Domenico Consoli, Monica Carletti, Jukka Putaala, Cataldo D'Amore, Nicola Mumoli, Maria Chondrogianni, Alberto Chiti, Peter Vanacker, Marialuisa Zedde, Michelangelo Mancuso, Boris Doronin, Giorgio Silvestrelli, Vanessa Gourbali, Simona Sacco, Manuel Cappellari, Giuseppe Martini, Christina Rueckert, Faisal Ibrahim, George Ntaios, Serena Monaco, Franco Galati, Antonio Carolei, Alessio Pieroni, Dorjan Zabzuni, Simona Marcheselli, Naveed Akhtar, Prasanna Tadi, Loris Poli, Mario Maimone Baronello, Antonio Baldi, Fabio Bandini, Vera Volodina, George Athanasakis, Yuriy Flomin, Chrysoula Liantinioti, Nicola Giannini, Umberto Scoditti, Elisa Giorli, Gayane Melikyan, Alessandro Pezzini, Alessia Lanari, Andrea Alberti, Konstantinos Makaritsis, Cindy Tiseo, Francesco Corea, Rossana Tassi, Georgios Tsivgoulis, Maria Luisa De Lodovici, Enrico Maria Lotti, Odysseas Kargiotis, Jessica Barlinn, Massimo Del Sette, Konstantinos Vadikolias, Paolo Bovi, Kennedy R. Lees, Riccardo Altavilla, Turgut Tatlisumak, Liisa Tomppo, Maurizio Paciaroni, Lilla Szabó, Alberto Rigatelli, Kristian Barlinn, Monica Acciarresi, Patrik Michel, Tiziana Tassinari, Maurizio Acampa, Maria Giulia Mosconi, Shadi Yaghi, Jessica Fusaro, Valeria Caso, Sebastiano D'Anna, Azmil H. Abdul-Rahim, Gino Gialdini, HUS Neurocenter, Department of Neurosciences, and Neurologian yksikkö

Subjects
anticoagulants, medicine.medical_specialty, LEUKOARAIOSIS, ARTERIAL TERRITORIES, 030204 cardiovascular system & hematology, 3124 Neurology and psychiatry, 03 medical and health sciences, 0302 clinical medicine, atrial fibrillation, humans, incidence, secondary prevention, Internal medicine, medicine, In patient, ACUTE ISCHEMIC-STROKE, Stroke, METAANALYSIS, Cerebral Hemorrhage, RISK, Advanced and Specialized Nursing, Secondary prevention, OUTCOMES, Cardioembolic stroke, Heparin, business.industry, Incidence (epidemiology), Low-Molecular-Weight, 3112 Neurosciences, Atrial fibrillation, HUMAN BRAIN, medicine.disease, Anticoagulants, Atrial Fibrillation, Heparin, Low-Molecular-Weight, Humans, Secondary Prevention, 3. Good health, Heparin.low molecular weight, 3121 General medicine, internal medicine and other clinical medicine, Cardiology, Human medicine, HEMORRHAGIC TRANSFORMATION, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background and Purpose— Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods— We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results— Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients ( P =0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4–3.7; P P =0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2–4.9; P =0.01) end points separately. Conclusions— Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Published
2019
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7. The clinical spectrum of reversible cerebral vasoconstriction syndrome: The Italian Project on Stroke at Young Age (IPSYS)

Author

Alessandro Padovani, Valeria De Giuli, Andrea Morotti, Alessandro Pezzini, Carlo Piantadosi, Carlo Gandolfo, Filomena Caria, Cristiano Azzini, Antonella Toriello, Piergiorgio Lochner, Alessandro Adami, Paolo Cerrato, Carlo Dallocchio, Maurizio Paciaroni, Cristina Motto, Serena Monaco, Valeria Bignamini, Loris Poli, Enrico Maria Lotti, Carla Zanferrari, Marialuisa Zedde, Alberto Chiti, Paolo Costa, Simona Marcheselli, Luca Quartuccio, Massimo Del Sette, Sabrina Anticoli, Maria Luisa DeLodovici, Anna Bersano, Maurizia Rasura, Sandro Sanguigni, Massimo Gamba, Maurizio Melis, Giorgio Silvestrelli, Fabio Melis, Mauro Gentile, Andrea Zini, and Corrado Lodigiani

Subjects
intracranial, medicine.medical_specialty, Headache Disorders, Primary, male, Neuroimaging, Internal medicine, primary, italy, middle aged, medicine, Vasospasm, Intracranial, humans, Stroke, vasospasm, Thunderclap headaches, reversible cerebral vasoconstriction syndrome (rcvs), business.industry, adult, stroke, thunderclap headache, female, headache disorders, primary, retrospective studies, syndrome, General Medicine, medicine.disease, Reversible cerebral vasoconstriction syndrome, Large cohort, Young age, headache disorders, Cardiology, Neurology (clinical), medicine.symptom, business, Vasoconstriction
Abstract

Introduction To describe clinical, neuroimaging, and laboratory features of a large cohort of Italian patients with reversible cerebral vasoconstriction syndrome. Methods In the setting of the multicenter Italian Project on Stroke at Young Age (IPSYS), we retrospectively enrolled patients with a diagnosis of definite reversible cerebral vasoconstriction syndrome according to the International Classification of Headache Disorders (ICHD)-3 beta criteria (6.7.3 Headache attributed to reversible cerebral vasoconstriction syndrome, imaging-proven). Clinical manifestations, neuroimaging, treatment, and clinical outcomes were evaluated in all patients. Characteristics of reversible cerebral vasoconstriction syndrome without typical causes (“idiopathic reversible cerebral vasoconstriction syndrome”) were compared with those of reversible cerebral vasoconstriction syndrome related to putative causative factors (“secondary reversible cerebral vasoconstriction syndrome”). Results A total of 102 patients (mean age, 47.2 ± 13.9 years; females, 85 [83.3%]) qualified for the analysis. Thunderclap headache at presentation was reported in 69 (67.6%) patients, and it typically recurred in 42 (60.9%). Compared to reversible cerebral vasoconstriction syndrome cases related to putative etiologic conditions (n = 21 [20.6%]), patients with idiopathic reversible cerebral vasoconstriction syndrome (n = 81 [79.4%]) were significantly older (49.2 ± 13.9 vs. 39.5 ± 11.4 years), had more frequently typical thunderclap headache (77.8% vs. 28.6%) and less frequently neurological complications (epileptic seizures, 11.1% vs. 38.1%; cerebral infarction, 6.1% vs. 33.3%), as well as concomitant reversible brain edema (25.9% vs. 47.6%). Conclusions Clinical manifestations and putative etiologies of reversible cerebral vasoconstriction syndrome in our series are slightly different from those observed in previous cohorts. This variability might be partly related to the coexistence of precipitating conditions with a putative etiologic role on disease occurrence.

Published
2019
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8. Clinical Features of Patients with Cervical Artery Dissection and Fibromuscular Dysplasia

Author

Sonia Bonacina, Mario Grassi, Marialuisa Zedde, Andrea Zini, Anna Bersano, Carlo Gandolfo, Giorgio Silvestrelli, Claudio Baracchini, Paolo Cerrato, Corrado Lodigiani, Simona Marcheselli, Maurizio Paciaroni, Maurizia Rasura, Manuel Cappellari, Massimo Del Sette, Anna Cavallini, Andrea Morotti, Giuseppe Micieli, Enrico Maria Lotti, Maria Luisa DeLodovici, Mauro Gentile, Mauro Magoni, Cristiano Azzini, Maria Vittoria Calloni, Elisa Giorli, Massimiliano Braga, Paolo La Spina, Fabio Melis, Rossana Tassi, Valeria Terruso, Rocco Salvatore Calabrò, Valeria Piras, Alessia Giossi, Martina Locatelli, Valentina Mazzoleni, Debora Pezzini, Sandro Sanguigni, Carla Zanferrari, Marina Mannino, Irene Colombo, Carlo Dallocchio, Patrizia Nencini, Valeria Bignamini, Alessandro Adami, Eugenio Magni, Rita Bella, Alessandro Padovani, Alessandro Pezzini, Rosario Pascarella, Maria Sessa, Emma Scelzo, Monica Laura Bandettini di Poggio, Francesca Boscain, Andrea Naldi, Valeria Caso, Massimo Gamba, Ilaria Casetta, Stefano Forlivesi, Giampaolo Tomelleri, Elena Schirinzi, Elena Verrengia, Graziamaria Nuzzaco, Sandro Beretta, Rossella Musolino, Daniele Imperiale, Maurizio Acampa, Antonio Gasparro, Maurizio Melis, Francesco Fisicaro, Ignazio Santilli, Manuel Corato, Marina Padroni, Eleonora Leuci, Federico Mazzacane, Alessandra Gaiani, Federica Assenza, Lucia Princiotta Cariddi, Cristina Sarti, Serena Monaco, Emanuele Puca, and Ludovico Ciolli

Subjects
Adult, Male, medicine.medical_specialty, demography, Adolescent, Cervical Artery, Migraine Disorders, Dissection (medical), Fibromuscular dysplasia, 030204 cardiovascular system & hematology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, cohort studies, Recurrence, Prevalence, medicine, Fibromuscular Dysplasia, Humans, risk factors, dissection, follow-up studies, Carotid Arteries, Female, Italy, Middle Aged, Proportional Hazards Models, Risk Factors, Stroke, Vertebral Artery Dissection, Advanced and Specialized Nursing, business.industry, Settore MED/09 - MEDICINA INTERNA, Follow up studies, medicine.disease, Neurology (clinical), Radiology, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Cohort study
Abstract

Background and Purpose: Observational studies have suggested a link between fibromuscular dysplasia and spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions have distinctive clinical characteristics has not been extensively investigated. Methods: In a cohort of consecutive patients with first-ever sCeAD, enrolled in the setting of the multicenter IPSYS CeAD study (Italian Project on Stroke in Young Adults Cervical Artery Dissection) between January 2000 and June 2019, we compared demographic and clinical characteristics, risk factor profile, vascular pathology, and midterm outcome of patients with coexistent cerebrovascular fibromuscular dysplasia (cFMD; cFMD+) with those of patients without cFMD (cFMD–). Results: A total of 1283 sCeAD patients (mean age, 47.8±11.4 years; women, 545 [42.5%]) qualified for the analysis, of whom 103 (8.0%) were diagnosed with cFMD+. In multivariable analysis, history of migraine (odds ratio, 1.78 [95% CI, 1.13–2.79]), the presence of intracranial aneurysms (odds ratio, 8.71 [95% CI, 4.06–18.68]), and the occurrence of minor traumas before the event (odds ratio, 0.48 [95% CI, 0.26–0.89]) were associated with cFMD. After a median follow-up of 34.0 months (25th to 75th percentile, 60.0), 39 (3.3%) patients had recurrent sCeAD events. cFMD+ and history of migraine predicted independently the risk of recurrent sCeAD (hazard ratio, 3.40 [95% CI, 1.58–7.31] and 2.07 [95% CI, 1.06–4.03], respectively) in multivariable Cox proportional hazards analysis. Conclusions: Risk factor profile of sCeAD patients with cFMD differs from that of patients without cFMD. cFMD and migraine are independent predictors of midterm risk of sCeAD recurrence.

Published
2021

9. A systematic review of neurological manifestations of SARS‐CoV‐2 infection: the devil is hidden in the details

Author

Ilijas Jelcic, Serena Monaco, Raphaël Bernard-Valnet, T. Akhvlediani, D. García Azorín, Michele Romoli, Johann Sellner, Pille Taba, Luca Mancinelli, University of Zurich, and Sellner, J

Subjects
Pediatrics, medicine.medical_specialty, Neurology, encephalitis, MEDLINE, Clinical Neurology, 610 Medicine & health, Disease, SARS‐CoV‐2, neuroinvasion, cerebrospinal fluid, neurological complications, 03 medical and health sciences, 0302 clinical medicine, COVID‐19, Epidemiology, medicine, Humans, 030212 general & internal medicine, medicine.diagnostic_test, business.industry, SARS-CoV-2, COVID-19, Magnetic resonance imaging, Original Articles, medicine.disease, Magnetic Resonance Imaging, 10040 Clinic for Neurology, ddc, 2728 Neurology (clinical), Infectious disease (medical specialty), 2808 Neurology, Original Article, Neurology (clinical), Nervous System Diseases, business, Meningitis, 030217 neurology & neurosurgery, Encephalitis
Abstract

BACKGROUND AND PURPOSE We systematically reviewed available evidence for reports of neurological signs and symptoms in patients with COVID-19 to identify cases with severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection or immune-mediated reaction in the nervous system. METHODS We followed PRISMA guidelines and used the MEDLINE, EMBASE, Google Scholar, MedRxiv and ChinaXiv databases to search for articles on COVID-19 and nervous system involvement that were published from 1 January to 24 April 2020. Data on design, sample size, neurological assessment and related work-up were extracted. Biases were assessed with the Newcastle-Ottawa scale. RESULTS We analysed 27 publications on potential neuroinvasive or parainfectious neurological complications of COVID-19. The reports focused on smell and taste (n = 5) and evaluation of neurological symptoms and signs in cohorts (n = 5). There were cases of Guillain-Barre syndrome/Miller-Fisher syndrome/cranial neuropathy (seven cases), meningitis/encephalitis (nine cases) and various other conditions (five cases). The number of patients with examination of cerebrospinal fluid and, in particular, SARS-CoV-2 polymerase chain reaction was negligible. Two had a positive SARS-CoV-2 polymerase chain reaction examination of cerebrospinal fluid specimen. Study of potential parenchymal involvement with magnetic resonance imaging was rare. Only four reports received a rating of the highest quality standards. CONCLUSIONS This systematic review failed to establish comprehensive insights into nervous system manifestations of COVID-19 beyond immune-mediated complications in the aftermath of respiratory symptoms. The authors therefore provide guidance for more careful clinical, diagnostic and epidemiological studies to characterize the manifestations and burden of neurological disease caused by SARS-CoV-2 on behalf of the Infectious Disease Panel of the European Academy of Neurology.

Published
2020

10. Safety of anticoagulation in patients treated with urgent reperfusion for ischemic stroke related to atrial fibrillation

Author

Antonio Baldi, Licia Denti, Kennedy R. Lees, Nicola Mumoli, Panagiotis Halvatsiotis, Massimo Del Sette, Alberto Chiti, Peter Vanacker, Marta Bellesini, Tiziana Tassinari, Paolo Bovi, Alessandro Padovani, Christina Rueckert, Jessica Barlinn, Dorjan Zabzuni, Cataldo D'Amore, Loris Poli, Maria Luisa De Lodovici, Federica Letteri, Odysseas Kargiotis, Manuel Cappellari, Prasanna Tadi, Turgut Tatlisumak, Cecilia Becattini, Ludovica Anna Cimini, Liisa Tomppo, Yuriy Flomin, Giancarlo Agnelli, Aikaterini Theodorou, Serena Monaco, Elena Ferrari, Rossana Tassi, Monica Acciarresi, Patrik Michel, Alessio Pieroni, Enrico Maria Lotti, Michele Venti, Walter Ageno, Sung Il Sohn, Leonardo Ulivi, Maurizio Paciaroni, Konstantinos Vadikolias, Jukka Putaala, Cindy Tiseo, Valeria Caso, Alessandro Pezzini, Giorgio Silvestrelli, Alfonso Ciccone, Francesco Corea, Lilla Szabó, Francesca Guideri, Martina Giuntini, Gianni Lorenzini, Efstathia Karagkiozi, Davide Imberti, Luca Masotti, Azmil H. Abdul-Rahim, Theodore Karapanayiotides, Alessia Lanari, Andrea Alberti, Simona Marcheselli, Vieri Vannucchi, Giuseppe Martini, Shadi Yaghi, Marialuisa Zedde, Michela Giustozzi, Karen L. Furie, Danilo Toni, Chrissoula Liantinioti, Dirk Deleu, Franco Galati, Elisa Giorli, Monica Carletti, Vanessa Gourbali, Michelangelo Mancuso, George Ntaios, George Athanasakis, Fabio Bandini, Vera Volodina, Nicola Giannini, Umberto Scoditti, Mario Maimone Baronello, Boris Doronin, Simona Sacco, Maria Giulia Mosconi, Georgios Tsivgoulis, László Csiba, Alberto Rigatelli, Kristian Barlinn, Konstantinos Makaritsis, Maurizio Acampa, and Giovanni Orlandi

Subjects
Male, anticoagulants, medicine.medical_specialty, medicine.medical_treatment, Hemorrhage, Brain Ischemia, Dabigatran, Brain ischemia, Internal medicine, 80 and over, medicine, Humans, atrial fibrillation, Prospective Studies, Prospective cohort study, Blood Coagulation, Stroke, Aged, thrombolytic therapy, Aged, 80 and over, Advanced and Specialized Nursing, Rivaroxaban, business.industry, Warfarin, Atrial fibrillation, Thrombolysis, Middle Aged, medicine.disease, secondary prevention, thrombectomy, Anticoagulants, Atrial Fibrillation, Female, Reperfusion, Thrombectomy, Thrombolytic Therapy, Treatment Outcome, Cardiology, Neurology (clinical), Human medicine, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50–1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53–2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation–related acute ischemic stroke, who started on oral anticoagulant.

Published
2020

11. Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation

Author

David, Seiffge, Gian Marco De Marchis, Masatoshi, Koga, Maurizio, Paciaroni, Duncan, Wilson, Manuel, Cappellari, Kosmas, Macha, Georgios, Tsivgoulis, Gareth, Ambler, Shoji, Arihiro, Leo, H Bonati, Bruno, Bonetti, Bernd, Kallmünzer, Keith, W Muir, Paolo, Bovi, Henrik, Gensicke, Manabu, Inoue, Stefan, Schwab, Shadi, Yaghi, Martin, M Brown, Philippe, Lyrer, Masahito, Takagi, Monica, Acciarrese, Hans Rolf Jager, Alexandros, A Polymeris, Kazunori, Toyoda, Michele, Venti, Christopher, Traenka, Hiroshi, Yamagami, Andrea, Alberti, Sohei, Yoshimura, Valeria, Caso, Stefan, T Engelter, David, J Werring, Kenichi, Todo, Kazumi, Kimura, Kensaku, Shibazaki, Yoshiki, Yagita, Eisuke, Furui, Ryo, Itabashi, Tadashi, Terasaki, Yoshiaki, Shiokawa, Teruyuki, Hirano, Rieko, Suzuki, Kenji, Kamiyama, Jyoji, Nakagawara, Shunya, Takizawa, Kazunari, Homma, Satoshi, Okuda, Yasushi, Okada, Koichiro, Maeda, Tomoaki, Kameda, Kazuomi, Kario, Yoshinari, Nagakane, Yasuhiro, Hasegawa, Hisanao, Akiyama, Satoshi, Shibuya, Hiroshi, Mochizuki, Yasuhiro, Ito, Takahiro, Nakashima, Hideki, Matsuoka, Kazuhiro, Takamatsu, Kazutoshi, Nishiyama, Kanta, Tanaka, Kaoru, Endo, Tetsuya, Miyagi, Masato, Osaki, Junpei, Kobayashi, Takuya, Okata, Eijiro, Tanaka, Yuki, Sakamoto, Keisuke, Tokunaga, Hotake, Takizawa, Junji, Takasugi, Soichiro, Matsubara, Kyoko, Higashida, Takayuki, Matsuki, Naoto, Kinoshita, Masayuki, Shiozawa, Toshihiro, Ide, Takeshi, Yoshimoto, Daisuke, Ando, Kyohei, Fujita, Masaya, Kumamoto, Teppei, Kamimura, Muneaki, Kikuno, Tadataka, Mizoguchi, Takeo, Sato, Karen, L Furie, Prasanna, Tadi, Cecilia, Becattini, Nicola, Falocci, Marialuisa, Zedde, Azmil, H Abdul-Rahim, Kennedy, R Lees, Cataldo, D’Amore, Maria, G Mosconi, Ludovica, A Cimini, Monica, Carletti, Alberto, Rigatelli, Jukka, Putaala, Liisa, Tomppo, Turgut, Tatlisumak, Fabio, Bandini, Simona, Marcheselli, Alessandro, Pezzini, Loris, Poli, Alessandro, Padovani, Luca, Masotti, Vieri, Vannucchi, Sung-Il, Sohn, Gianni, Lorenzini, Rossana, Tassi, Francesca, Guideri, Maurizio, Acampa, Giuseppe, Martini, George, Ntaios, Efstathia, Karagkiozi, George, Athanasakis, Kostantinos, Makaritsis, Kostantinos, Vadikolias, Chrysoula, Liantinioti, Maria, Chondrogianni, Nicola, Mumoli, Domenico, Consoli, Franco, Galati, Simona, Sacco, Antonio, Carolei, Cindy, Tiseo, Francesco, Corea, Walter, Ageno, Marta, Bellesini, Giorgio, Silvestrelli, Alfonso, Ciccone, Umberto, Scoditti, Licia, Denti, Mancuso, Michelangelo, Miriam, Maccarrone, Orlandi, Giovanni, Nicola, Giannini, Gino, Gialdini, Tiziana, Tassinari, Maria Luisa De Lodovici, Giorgio, Bono, Christina, Rueckert, Antonio, Baldi, Danilo, Toni, Federica, Letteri, Martina, Giuntini, Enrico, M Lotti, Yuriy, Flomin, Alessio, Pieroni, Odysseas, Kargiotis, Theodore, Karapanayiotides, Serena, Monaco, 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, P Pallesen, Ulf, Bodechtel, Leonardo, Ulivi, Dirk, Deleu, Gayane, Melikyan, Jessica, Bourlinn, Naveed, Akhar, Falsal, Ibrahin, Gourbali, Vanessa, Hawone, Baronello, Lisa, Hert, Nils, Peters, Marina, Maurer, and Martina, Wiegert

Subjects
0301 basic medicine, medicine.medical_specialty, Vascular disease, business.industry, Hazard ratio, Ischemia, 610 Medicine & health, Atrial fibrillation, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Neurology, Interquartile range, Internal medicine, Heart failure, medicine, Neurology (clinical), Prospective cohort study, business, Stroke, 030217 neurology & neurosurgery, Research Articles, Research Article
Abstract

Objective:\ud It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.\ud \ud Methods:\ud We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).\ud \ud Results:\ud We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585).\ud \ud Interpretation:\ud Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group.

Published
2019
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12. Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke

Author

Karen L. Furie, Franco Galati, Antonio Carolei, Simona Sacco, Naveed Akhtar, Andrea Alberti, Vanessa Gourbali, Elisa Giorli, Federica Letteri, Filippo Angelini, Georgios Tsivgoulis, Simona Marcheselli, L.-P. Pallesen, Nicola Falocci, Serena Monaco, Giovanni Orlandi, Maria Luisa De Lodovici, Maria Giulia Mosconi, Michele Venti, Walter Ageno, Mario Maimone Baronello, László Csiba, Alfonso Ciccone, Odysseas Kargiotis, Kostantinos Vadikolias, Massimo Del Sette, Chrysoula Liantinioti, Maurizio Paciaroni, Valeria Caso, Cecilia Becattini, Danilo Toni, Peter Vanacker, Alessandro Padovani, Azmil H. Abdul-Rahim, Gino Gialdini, Christina Rueckert, Patrik Michel Pd-Mer, Giorgio Silvestrelli, Marialuisa Zedde, Cataldo D'Amore, Sung Il Sohn, Monica Acciarresi, Monica Carletti, George Ntaios, Kennedy R. Lees, Maria Chondrogianni, Gayane Melikyan, Domenico Consoli, Faisal Ibrahim, Francesca Guideri, Martina Giuntini, Alessandro Pezzini, Fabio Bandini, Vera Volodina, Alberto Rigatelli, Kristian Barlinn, Luca Masotti, Licia Denti, Boris Doronin, Tiziana Tassinari, Cindy Tiseo, Dorjan Zabzuni, Alberto Chiti, Francesco Corea, Nicola Giannini, Loris Poli, Nicola Mumoli, Jessica Kepplinger, Maurizio Acampa, Riccardo Altavilla, George Athanasakis, Theodore Karapanayiotides, Antonio Baldi, Prasanna Tadi, Umberto Scoditti, Turgut Tatlisumak, Yuriy Flomin, Rossana Tassi, Michelangelo Mancuso, Liisa Tomppo, Vieri Vannucchi, Efstathia Karagkiozi, Davide Imberti, Enrico Maria Lotti, Alessio Pieroni, Lilla Szabó, Dirk Deleu, Giancarlo Agnelli, Giorgio Bono, Miriam Maccarrone, Jukka Putaala, Giuseppe Martini, Marta Bellesini, Shadi Yaghi, Ludovica Anna Cimini, Gianni Lorenzini, K. Makaritsis, Paolo Bovi, Manuel Cappellari, HUS Neurocenter, Department of Neurosciences, Neurologian yksikkö, and University of Helsinki

Subjects
medicine.medical_specialty, ANTICOAGULATED PATIENTS, anticoagulation, atrial fibrillation, paroxysmal atrial fibrillation, Stroke, stroke recurrence, sustained atrial fibrillation, Early Recurrence, Paroxysmal atrial fibrillation, Stroke recurrence, macromolecular substances, 030204 cardiovascular system & hematology, 3124 Neurology and psychiatry, EVENTS, 03 medical and health sciences, PERSISTENT, 0302 clinical medicine, Original Research Articles, Internal medicine, Ischaemic stroke, medicine, ORAL ANTICOAGULATION, In patient, cardiovascular diseases, Prospective cohort study, OUTCOMES, business.industry, DEATH, 3112 Neurosciences, Atrial fibrillation, medicine.disease, PATTERN, Cardiology, cardiovascular system, Human medicine, Neurology (clinical), HIGHER RISK, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

Background The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. Purpose In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. Methods In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. Results A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24–2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74–2.04)). Conclusions After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.

Published
2019

13. Prestroke CHA2DS2-VASc Score and Severity of Acute Stroke in Patients with Atrial Fibrillation: Findings from RAF Study

Author

Umberto Scoditti, Suzette Remillard, Maria Giulia Mosconi, Serena Monaco, Giancarlo Agnelli, Maurizio Paciaroni, Dorjan Zabzuni, Boris Doronin, Giorgio Bono, Simona Sacco, Ulf Bodechtel, Simona Marcheselli, Maria Luisa De Lodovici, Kennedy R. Lees, Alessio Pieroni, Lilla Szabó, Gianni Lorenzini, Cecilia Becattini, Nicola Falocci, Tiziana Tassinari, Jukka Putaala, Peter Vanacker, László Csiba, Giovanni Orlandi, Maria Cordier, Giuseppe Martini, Danilo Toni, Domenico Consoli, Christina Rueckert, Davide Imberti, Chrissoula Liantinioti, Monica Acciarresi, Paolo Costa, Sung Il Sohn, Monica Carletti, Dirk Deleu, Johannes Gerber, Francesca Guideri, Paolo Bovi, Rossana Tassi, Luca Masotti, Alberto Chiti, Licia Denti, Valeria Caso, Georgios Tsivgoulis, Antonio Baldi, Naveed Akhtar, Massimo Del Sette, Alberto Rigatelli, Kristian Barlinn, Cindy Tiseo, Franco Galati, Antonio Carolei, Andrea Morotti, Alessandro Pezzini, Francesco Corea, Patrik Michel, Vera Volodina, Cataldo D'Amore, Lars-Peder Pallesen, Andrea Alberti, Faisal Ibrahim, Mario Maimone Baronello, Jessica Kepplinger, Sebastiano D'Anna, Azmil H. Abdul-Rahim, Michele Venti, Walter Ageno, Gino Gialdini, Kostantinos Vadikolias, Gayane Melikyan, Turgut Tatlisumak, Alessandro Padovani, Neurologian yksikkö, Department of Neurosciences, Clinicum, University of Helsinki, and HUS Neurocenter

Subjects
Male, atrial fibrillation, CHA, 2, DS, VASc score, Ischemic stroke, outcome, scores, severity, Aged, Aged, 80 and over, Area Under Curve, Asia, Atrial Fibrillation, Chi-Square Distribution, Disability Evaluation, Europe, Female, Humans, Linear Models, Logistic Models, Magnetic Resonance Imaging, Multivariate Analysis, Odds Ratio, Predictive Value of Tests, Prognosis, Prospective Studies, ROC Curve, Risk Assessment, Risk Factors, Severity of Illness Index, Stroke, Time Factors, Tomography, X-Ray Computed, Decision Support Techniques, CHA2DS2-VASc score, Surgery, Rehabilitation, Neurology (clinical), Cardiology and Cardiovascular Medicine, ARTERIAL TERRITORIES, 030204 cardiovascular system & hematology, Logistic regression, CHADS(2), 3124 Neurology and psychiatry, 0302 clinical medicine, Modified Rankin Scale, 80 and over, Medicine, Elméleti orvostudományok, ACUTE ISCHEMIC-STROKE, Prospective cohort study, Tomography, OUTCOMES, Area under the curve, Atrial fibrillation, Orvostudományok, HUMAN BRAIN, X-Ray Computed, CHA(2)DS(2)-VASc score, Cardiology, medicine.medical_specialty, education, macromolecular substances, 03 medical and health sciences, Internal medicine, cardiovascular diseases, ischemic stroke, surgery, rehabilitation, neurology (clinical), cardiology and cardiovascular medicine, Receiver operating characteristic, business.industry, 3112 Neurosciences, medicine.disease, 3121 General medicine, internal medicine and other clinical medicine, CHA2DS2–VASc score, Physical therapy, Human medicine, business, 030217 neurology & neurosurgery
Abstract

Background and Purpose: The aim of this study was to investigate for a possible association between both prestroke CHA(2)DS(2)-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). Methods: This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2DS2-VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS >= 10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS = 3). Multiple logistic regression was used to correlate prestroke CHA(2)DS(2)-VASc and severity of stroke, as well as disability and mortality at 90 days. Results: Of the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS >= 3. A linear correlation was found between the prestroke CHA(2)DS(2)-VASc score and severity of stroke (P = .001). On multivariate analysis, CHA(2)DS(2)-VASc score correlated with severity of stroke (P = .041) and adverse functional outcome (mRS = 3) (P = .001). A logistic regression with the receiver operating characteristic graph procedure (C-statistics) evidenced an area under the curve of .60 (P = .0001) for severe stroke. Furthermore, a correlation was found between prestroke CHA(2)DS(2)-VASc score and lesion size. Conclusions: In patients with AF, in addition to the risk of stroke, a high CHA(2)DS(2)-VASc score was independently associated with both stroke severity at onset and disability and mortality at 90 days.

Published
2017

14. Myocardial Infarction Following Intravenous Thrombolysis for Acute Ischemic Stroke: Case Report and Literature Review

Author

Serena Monaco, Melchiorre Gilberto Cellura, Matilde Gammino, Marina Mannino, Salvatore Asciutto, and Valeria Terruso

Subjects
medicine.medical_specialty, medicine.medical_treatment, Embolism, Anterior myocardial infarction, 030204 cardiovascular system & hematology, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Fatal Outcome, Fibrinolytic Agents, Internal medicine, Medicine, Humans, Thrombolytic Therapy, cardiovascular diseases, Myocardial infarction, Infusions, Intravenous, Acute ischemic stroke, Stroke, Anterior Wall Myocardial Infarction, Aged, business.industry, Rehabilitation, Thrombolysis, medicine.disease, Tissue Plasminogen Activator, Cardiology, Surgery, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

Embolic complications of intravenous thrombolysis for acute ischemic stroke are increasingly recognized, and to date several cases of myocardial infarction soon after the administration of alteplase have been reported. We describe a case of early anterior myocardial infarction during intravenous thrombolysis for stroke and review the current literature.

Published
2016

15. Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study

Author

Francesca Guideri, Martina Giuntini, Luca Masotti, Alessandro Padovani, Danilo Toni, Maria Chondrogianni, Monica Carletti, Cecilia Becattini, Dorjan Zabzuni, Loris Poli, Theodore Karapanayiotides, Monica Acciarresi, Antonio Procopio, Giuseppe Martini, Giovanni Orlandi, Maurizio Acampa, Nicola Falocci, Vieri Vannucchi, Valeria Caso, Cindy Tiseo, Enrico Maria Lotti, László Csiba, Giancarlo Agnelli, Michelangelo Mancuso, Giorgio Bono, Lilla Szabó, Antonio Baldi, Serena Monaco, Jukka Putaala, Faisal Ibrahim, Dirk Deleu, Prasanna Tadi, Yuriy Flomin, Miriam Maccarrone, Georgios Tsivgoulis, Kennedy R. Lees, George Ntaios, Massimo Del Sette, Alberto Rigatelli, Kristian Barlinn, Naveed Akhtar, Jessica Kepplinger, Simona Sacco, Fabio Bandini, Vera Volodina, Lars-Peder Pallesen, Rossana Tassi, Odysseas Kargiotis, Peter Vanacker, Tiziana Tassinari, Nicola Giannini, Christina Rueckert, Ulf Bodechtel, Elisa Giorli, Simona Marcheselli, Efstathia Karagkiozi, Davide Imberti, Michele Venti, Walter Ageno, Chrysoula Liantinioti, Kostantinos Vadikolias, Alfonso Ciccone, Federica Letteri, Domenico Consoli, Andrea Alberti, Turgut Tatlisumak, Marialuisa Zedde, Vanessa Gourbali, Alberto Chiti, Manuel Cappellari, Cataldo D'Amore, Alessandro Pezzini, Francesco Corea, Maurizio Paciaroni, Liisa Tomppo, Giorgio Silvestrelli, Gayane Melikyan, Gianni Lorenzini, K. Makaritsis, Paolo Bovi, Marta Bellesini, Patrik Michel, Ludovica Anna Cimini, Alessio Pieroni, Shadi Yaghi, Sebastiano D'Anna, Azmil H. Abdul-Rahim, Gino Gialdini, Licia Denti, Nicola Mumoli, Mario Maimone Baronello, Maria Luisa De Lodovici, Sung Il Sohn, Johannes Gerber, Giovanna Colombo, Boris Doronin, Karen L. Furie, Franco Galati, Antonio Carolei, Maria Giulia Mosconi, George Athanasakis, and Umberto Scoditti

Subjects
Male, medicine.medical_specialty, atrial fibrillation, myocardial infarction, risk stratification, stroke, Hemorrhage, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Thromboembolism, Atrial Fibrillation, 80 and over, Medicine, Humans, Myocardial infarction, Aged, Aged, 80 and over, Anticoagulants, Female, Ischemic Attack, Transient, Prospective Studies, Stroke, Warfarin, Prospective cohort study, Advanced and Specialized Nursing, business.industry, Ischemic Attack, Transient, Neurology (clinical), Cardiology and Cardiovascular Medicine, atrial fibrillation, myocardial infarction, risk stratification, stroke, Atrial fibrillation, medicine.disease, Cardiology, Observational study, Human medicine, business, Risk assessment, Complication, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background and Purposes— This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods— The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P =0.10) for major bleedings. Results— The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P =0.009) for ischemic outcome events and 0.407 (0.275–0.540; P =0.14) for hemorrhagic outcome events. Conclusions— In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.

Published
2016

16. Contents Vol. 34, 2012

Author

Toshiho Ohtsuki, Druck Reinhardt Druck Basel, Alessandro Pezzini, Danilo Toni, Stephen Meairs, Karin Ernstrom, Hisashi Masugata, Simon Jung, S. Domènech, Heinrich Mattle, Valeria Caso, Luca Remonda, Giovanni Orlandi, Katsuhiko Matsuo, Takeshi Aoki, Randolph S. Marshall, Michael G. Hennerici, Joanna M. Wardlaw, Hiroaki Dobashi, Akira Ogawa, Xin Wang, Hidetoshi Matsukawa, Yasushi Okada, Mauro Silvestrini, Gino Gialdini, Oliver Findling, Manuel Cappellari, Koji Murao, Hideki Origasa, Eric Jouvent, Russell V. Luepker, Naoki Nakayama, A. Dávalos, Takanari Kitazono, Masakazu Kobayashi, Kazushi Deguchi, Marco Duering, Nassira Allili, Patrizia Nencini, Karen C. Albright, P. Cuadras, Andrea Zini, Dawn M Meyer, Alexander Karameshev, David Rodriguez-Luna, Alessandro Padovani, Osamu Yasuda, Alessio Pieroni, David S Liebeskind, Brett C. Meyer, Giorgio Bono, Yuichi Izumi, Ekkehart Jenetzky, Carlo Ferrarese, Francesca M Chappell, Claudia Trentini, Giampiero Galletti, Kenji Yoshida, Werner Hacke, Hiroyuki Imamura, Sean I Savitz, Joseph P. Broderick, Masahito Katoh, Marcia Spindler, Ivânia Alves, David C. Anderson, Naohisa Hosomi, Michele Venti, Markus A Möhlenbruch, Ming Yao, Falk Mueller-Riemenschneider, Saqib A Chaudhry, Wondwossen G Tekle, E. López-Cancio, Rakesh Khatri, José Alvarez-Sabín, Tiziana Tassinari, Takenori Yamaguchi, Hiroki Kuroda, Rossana Tassi, Timolaos Rizos, José G. Merino, Kohsuke Kudo, Gerhard Schroth, Carole Stuker, Marc Ribó, Cataldo D’Amore, Atsushi Murakata, Maria del C. Valdés Hernández, Carlos Veira, Kiyohiro Houkin, Tomohisa Nezu, M. Millán, Masahiro Kamouchi, Toshimitsu Aida, Christoph Gumbinger, Luis Ruano, Kuniaki Ogasawara, Takeo Abumiya, Julie Staals, Rema Raman, Roland Veltkamp, Gian Marco De Marchis, Stefan N. Willich, Alfonso Ciccone, Andria L. Ford, Hirofumi Soejima, Masayasu Matsumoto, Adnan I Qureshi, Àngels Pedragosa, Hisao Ogawa, Makoto Sasaki, Albert W Tsai, Caroline M. J. Loos, Joan Brugués, Motoharu Fujii, Masaki Shinoda, A. Massuet, Olga Maisterra, Maria Luisa DeLodovici, Shiro Aoki, Junko Tanaka, Alessia Lanari, Andrea Alberti, Osamu Takahashi, M. Gomis, Fergus N. Doubal, Satz Mengensatzproduktion, Rudolf Luedi, Hideo Ohyama, Shunrou Fujiwara, Krassen Nedeltchev, Giancarlo Agnelli, Andrei V. Alexandrov, Paolo Frigio Nichelli, Sheryl Martin-Schild, Isabel Araújo, Marta Rubiera, M. Hernández-Pérez, Marie-Luise Mono, Ameer E Hassan, Ximena Castillo, Paolo Bovi, Emilio Luda, Massimo Del Sette, Martin Dichgans, C. Berthet, Paolo Previdi, Robert J. van Oostenbrugge, Vítor Tedim Cruz, Maurizio Riva, Dawn Kleindorfer, Taro Suzuki, Naoko Kumagai, Noriko Ichihara, N. Pérez de la Ossa, Rui Barreto, Peter A. Ringleb, Mascia Nesi, Solveig Horstmann, Domenico Consoli, Domenico Inzitari, Alberto Chiti, Marcel Arnold, Natalia S. Rost, Giuseppe Martini, Carlos A. Molina, Stephan Rieks, Takuya Moriwaki, Kamakshi Lakshminarayan, Raffaella Cerqua, Maurizio Paciaroni, Lorenz Hirt, Claus Kiefer, Marwan El-Koussy, Elisabetta Traverso, Hideaki Nishimoto, Masakazu Kohno, Simone Beretta, Dominique Hervé, Johannes Slotboom, Ryoichi Ishikawa, Masami Yoshino, Giorgio Silvestrelli, Pierre J. Magistretti, Serena Monaco, Aekaterini Galimanis, Monica Acciarresi, James M. Peacock, L. Dorado, Simona Marcheselli, Hugues Chabriat, and Takamasa Nanba

Subjects
Neurology, Traditional medicine, business.industry, Medicine, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Published
2012
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17. Plasma levels of inflammatory and thrombotic/fibrinolytic markers in acute ischemic strokes: Relationship with TOAST subtype, outcome and infarct site

Author

Giuseppe Licata, Antonia Serio, Antonino Tuttolomondo, Riccardo Di Sciacca, Domenico Di Raimondo, Gisella D'Aguanno, Serena Monaco, Eraldo Natalè, Sergio La Placa, Valentina Arnao, Luciana Marino, Rosaria Pecoraro, Antonio Pinto, Tuttolomondo, A, Di Sciacca, R, Di Raimondo, D, Serio, A, D’Aguanno, G, La Placa, S, Percoraro, R, Arnao, V, Marino, L, Monaco, S, Natalè, E, Licata, G, and Pinto, A

Subjects
Male, medicine.medical_specialty, stroke, TOAST subtype, Immunology, Inflammation, Gastroenterology, Brain Ischemia, Internal medicine, medicine, Humans, Immunology and Allergy, In patient, Acute ischemic stroke, Stroke, Aged, Neurological deficit, Aged, 80 and over, business.industry, Fibrinolysis, Ischemic strokes, Cerebral Infarction, Plasma levels, Middle Aged, medicine.disease, Neurology, Physical therapy, Female, Neurology (clinical), Inflammation Mediators, Intracranial Thrombosis, medicine.symptom, business, Biomarkers
Abstract

BACKGROUND: The aim of our study was to evaluate in patients with acute ischemic stroke the relationship between immuno-inflammatory variables, clinical outcome and infarct site. MATERIALS AND METHODS: We evaluated plasma levels of IL-1beta, TNF-alpha, IL-6 and IL-10, E-selectin, P-selectin, sICAM-1 ,sVCAM-1 vWF, TPA and PAI-1. RESULTS: Patients with cardioembolic subtype showed significantly higher median plasma levels of TNF-alpha, IL-6, IL-1beta whereas the lacunar subtype showed significantly lower median plasma levels of TNF-alpha, IL-6 and IL-1beta. CONCLUSIONS: A significant association was noted between the severity of neurological deficit at admission, the diagnostic subtype and some inflammatory variables.

Published
2009
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18. Prognostic value of trans-thoracic echocardiography in patients with acute stroke and atrial fibrillation: findings from the RAF study

Author

Domenico Consoli, Alberto Chiti, Antonio Baldi, Massimo Del Sette, Alessandro Padovani, Cecilia Becattini, Kostantinos Vadikolias, Vera Volodina, Patrik Michel, Chrissoula Liantinioti, Davide Imberti, Naveed Akhtar, Cataldo D'Amore, Umberto Scoditti, Simona Sacco, Dirk Deleu, Michele Venti, Walter Ageno, Cindy Tiseo, Serena Monaco, Turgut Tatlisumak, Paolo Bovi, Valeria Caso, Francesca Guideri, Ulf Bodechtel, Luca Masotti, Faisal Ibrahim, Sebastiano D'Anna, Dorjan Zabzuni, Loris Poli, Azmil H. Abdul-Rahim, Kennedy R. Lees, Boris Doronin, Gino Gialdini, Lilla Szabó, Gayane Melikyan, Alberto Rigatelli, Kristian Barlinn, Giuseppe Martini, Alessio Pieroni, Tiziana Tassinari, Andrea Alberti, Nicola Falocci, Gianni Lorenzini, Jessica Kepplinger, Peter Vanacker, Maria Giulia Mosconi, Lars-Peder Pallesen, Christina Rueckert, Monica Acciarresi, Mario Maimone Baronello, Suzette Remillard, Danilo Toni, Rossana Tassi, Monica Carletti, Maurizio Paciaroni, Simona Marcheselli, Giancarlo Agnelli, László Csiba, Giorgio Bono, Jukka Putaala, Georgios Tsivgoulis, Johannes Gerber, Alessandro Pezzini, Francesco Corea, Giovanni Orlandi, Maria Cordier, Franco Galati, Antonio Carolei, Maria Luisa De Lodovici, Sung Il Sohn, and Licia Denti

Subjects
Male, medicine.medical_specialty, Neurology, Atrial enlargement, 030204 cardiovascular system & hematology, Klinikai orvostudományok, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Risk Factors, Internal medicine, medicine, Left atrial enlargement, Secondary Prevention, Humans, Acute stroke, cardiovascular diseases, Stroke, Neuroradiology, Aged, Acute stroke, Atrial fibrillation, Echocardiography, Outcome, Outcome, business.industry, Atrial fibrillation, Orvostudományok, medicine.disease, Prognosis, Thrombosis, Echocardiography, Atrial Fibrillation, Female, Neurology (clinical), Cardiology, Human medicine, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Anticoagulant therapy is recommended for the secondary prevention of stroke in patients with atrial fibrillation (AF). T he identification of patients at high risk for early recurrence, which are potential candidates to prompt anticoagulation, is crucial to justify the risk of bleeding associated with early anticoagulant treatment. The aim of this study was to evaluate in patients with acute ischemic stroke and AF the association between findings at trans-thoracic echocardiography (TTE) and 90 days recurrence. In consecutive patients with acute ischemic stroke and AF, TTE was performed within 7 days from hospital admission. Study outcomes were recurrent ischemic cerebrovascular events (stroke or TIA) and systemic embolism. 854 patients (mean age 76.3 +/- A 9.5 years) underwent a TTE evaluation; 63 patients (7.4 %) had at least a study outcome event. Left atrial thrombosis was present in 11 patients (1.3 %) among whom 1 had recurrent ischemic event. Left atrial enlargement was present in 548 patients (64.2 %) among whom 51 (9.3 %) had recurrent ischemic events. The recurrence rate in the 197 patients with severe left atrial enlargement was 11.7 %. On multivariate analysis, the presence of atrial enlargement (OR 2.13; 95 % CI 1.06-4.29, p = 0.033) and CHA(2)DS(2)-VASc score (OR 1.22; 95 % CI 1.04-1.45, p = 0.018, for each point increase) were correlated with ischemic recurrences. In patients with AF-associated acute stroke, left atrial enlargement is an independent marker of recurrent stroke and systemic embolism. The risk of recurrence is accounted for by severe atrial enlargement. TTE-detected left atrial thrombosis is relatively uncommon.

Published
2016

19. Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Author

László Csiba, Francesca Guideri, Luca Masotti, Davide Imberti, Sokratis G. Papageorgiou, Dorjan Zabzuni, Giancarlo Agnelli, Loris Poli, Sebastiano D'Anna, Azmil H. Abdul-Rahim, Gino Gialdini, Umberto Scoditti, Giorgio Bono, Naveed Akhtar, Gianni Lorenzini, Alessandro Padovani, Dirk Deleu, Serena Monaco, Nicola Falocci, Cecilia Becattini, Jukka Putaala, Simona Sacco, Patrik Michel, Alberto Rigatelli, Kristian Barlinn, Maria Luisa De Lodovici, Gayane Melikyan, Ulf Bodechtel, Georgios Tsivgoulis, Boris Doronin, Cindy Tiseo, Monica Acciarresi, Alessandro Pezzini, Lilla Szabó, Rossana Tassi, Francesco Corea, Giovanni Orlandi, Maria Giulia Mosconi, Maria Cordier, Paolo Bovi, Licia Denti, Valeria Caso, Turgut Tatlisumak, Sung Il Sohn, Simona Marcheselli, Alessio Pieroni, Mario Maimone Baronello, Suzette Remillard, Maurizio Paciaroni, Danilo Toni, Cataldo D'Amore, Kateryna Antonenko, Monica Carletti, Antonio Baldi, Peter Vanacker, Christina Rueckert, Kennedy R. Lees, Michele Venti, Walter Ageno, Andrea Alberti, Lars-Peder Pallesen, Tiziana Tassinari, Johannes Gerber, Faisal Ibrahim, Domenico Consoli, Jessica Kepplinger, Kostantinos Vadikolias, Alberto Chiti, Massimo Del Sette, Vera Volodina, Franco Galati, Antonio Carolei, and Giuseppe Martini

Subjects
medicine.medical_specialty, anticoagulation therapy, atrial fibrillation, ischemic stroke, secondary prevention, Sex differences, stroke outcome, Early Recurrence, Internal medicine, Original Research Articles, Medicine, In patient, cardiovascular diseases, Risk factor, Acute ischemic stroke, Stroke, Fibrillation, business.industry, Atrial fibrillation, medicine.disease, Cardiology, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, Cerebral Bleeding
Abstract

Introduction Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results Of the 1029 patients enrolled, 561 were women (54.5%) ( p Conclusions Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes.

Published
2016

20. Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study

Author

Kennedy R. Lees, Alessandro Pezzini, Francesco Corea, Tiziana Tassinari, Lars-Peder Pallesen, Suzette Remillard, Maria Cordier, Cecilia Becattini, Maria Luisa De Lodovici, Peter Vanacker, Alessandro Padovani, Simona Marcheselli, Maurizio Paciaroni, Christina Rueckert, Domenico Consoli, Serena Monaco, Sung Il Sohn, Cindy Tiseo, Cataldo D'Amore, Johannes Gerber, Alberto Chiti, Vera Volodina, Kostantinos Vadikolias, Paolo Bovi, Massimo Del Sette, Licia Denti, Dorjan Zabzuni, Loris Poli, Faisal Ibrahim, Nicola Falocci, Andrea Alberti, Michele Venti, Walter Ageno, Giancarlo Agnelli, Franco Galati, Antonio Carolei, Antonio Baldi, Mario Maimone Baronello, Valentina Bubba, Danilo Toni, Giorgio Bono, Jessica Kepplinger, Gianni Lorenzini, Gayane Melikyan, Monica Carletti, Jukka Putaala, Ilenia Silvestri, Chrissoula Liantinioti, Giovanni Orlandi, Dirk Deleu, Turgut Tatlisumak, Sebastiano D'Anna, Rossana Tassi, Alessio Pieroni, Davide Imberti, Azmil H. Abdul-Rahim, Gino Gialdini, Giuseppe Martini, Valeria Caso, Naveed Akhtar, Lilla Szabó, Francesca Guideri, Luca Masotti, Monica Acciarresi, Umberto Scoditti, Maria Giulia Mosconi, Boris Doronin, Patrik Michel, Simona Sacco, Ulf Bodechtel, Alberto Rigatelli, Kristian Barlinn, László Csiba, and Georgios Tsivgoulis

Subjects
Male, Time Factors, Brain Ischemia, Brain ischemia, Cohort Studies, Recurrence, Risk Factors, Atrial Fibrillation, 80 and over, hemorrhagic stroke, Prospective Studies, Prospective cohort study, Stroke, anticoagulant therapy, atrial fibrillation, ischemic stroke, secondary prevention, Aged, Aged, 80 and over, Anticoagulants, Cerebral Hemorrhage, Female, Follow-Up Studies, Humans, Middle Aged, Treatment Outcome, Medicine (all), Atrial fibrillation, Orvostudományok, 3. Good health, Cardiology, Anticoagulant therapy, Hemorrhagic stroke, Ischemic stroke, Secondary prevention, Neurology (clinical), Cardiology and Cardiovascular Medicine, Advanced and Specialized Nursing, Cohort study, medicine.medical_specialty, Klinikai orvostudományok, Anticoagulant therapy, Atrial fibrillation, Hemorrhagic stroke, Ischemic stroke, Secondary prevention, Internal medicine, medicine, business.industry, medicine.disease, Surgery, Human medicine, Cerebral Bleeding, business
Abstract

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively ( P =0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Published
2015

21. The THRombolysis and STatins (THRaST) study

Author

Giampiero Galletti, Rinaldo M. Colombo, Vincenzo Di Lazzaro, Maria Concetta Altavista, Umberto Scoditti, Daniele Orrico, Maria Sessa, Gaetano Procaccianti, Massimo Del Sette, Manuel Cappellari, Fabio Brusaferri, Giuseppe Moretto, Giuseppe Martini, Gabriele Greco, Serena Monaco, Alessandro Adami, Andrea Zini, Fabio Chiodo-Grandi, Claudio Grassa, Paolo Bovi, Maria Guarino, Domenico Consoli, Anna Cavallini, Maria Vittoria Calloni, Mauro Zampolini, Tiziana Tassinari, Simone Beretta, Francesco Federico, Danilo Toni, Luigi Maria Specchio, Maurizio Paciaroni, Maurizia Rasura, Carlo Gandolfo, Simona Marcheselli, Armando Mancini, Alessandro Pezzini, Marco Sparaco, Bruno Passarella, Maurizio Melis, Giorgio Silvestrelli, Rossella Sciolla, Mauro Furlan, Giovanni Orlandi, L. Adobbati, Luigi Bettoni, Patrizia Nencini, Maria Roberta Bongioanni, Cappellari, M, Bovi, P, Moretto, G, Zini, A, Nencini, P, Sessa, M, Furlan, M, Pezzini, A, Orlandi, G, Paciaroni, M, Tassinari, T, Procaccianti, G, Di Lazzaro, V, Bettoni, L, Gandolfo, C, Silvestrelli, G, Rasura, M, Martini, G, Melis, M, Calloni, M, Chiodo Grandi, F, Beretta, S, Guarino, M, Altavista, M, Marcheselli, S, Galletti, G, Adobbati, L, Del Sette, M, Mancini, A, Orrico, D, Monaco, S, Cavallini, A, Sciolla, R, Federico, F, Scoditti, U, Brusaferri, F, Grassa, C, Specchio, L, Bongioanni, M, Sparaco, M, Zampolini, M, Greco, G, Colombo, R, Passarella, B, Adami, A, Consoli, D, and Toni, D

Subjects
Male, Multivariate analysis, Time Factors, medicine.medical_treatment, Severity of Illness Index, non presente, Retrospective Studie, Modified Rankin Scale, Outcome Assessment, Health Care, 80 and over, Prospective Studies, Multivariate Analysi, Stroke, Aged, 80 and over, Neurologic Examination, Fibrinolytic Agent, Thrombolysis, Middle Aged, stroke, X-Ray Computed, Tissue Plasminogen Activator, Cardiology, Female, Human, medicine.medical_specialty, thrombolysis, Tomography Scanners, X-Ray Computed, Logistic Model, Time Factor, Article, Outcome Assessment (Health Care), Arts and Humanities (miscellaneous), Fibrinolytic Agents, Internal medicine, medicine, Humans, cardiovascular diseases, Aged, Retrospective Studies, Intracerebral hemorrhage, Tomography Scanners, business.industry, Odds ratio, medicine.disease, Confidence interval, Surgery, Prospective Studie, Logistic Models, Multicenter study, Multivariate Analysis, Hydroxymethylglutaryl-CoA Reductase Inhibitor, Neurology (clinical), Hydroxymethylglutaryl-CoA Reductase Inhibitors, business
Abstract

Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis. Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death. Results: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26-2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11-1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18-2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19-0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28-0.82; p = 0.007). Conclusion: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome. © 2013 American Academy of Neurology.

Published
2013

22. Intravenous thrombolysis for acute ischemic stroke associated to extracranial internal carotid artery occlusion: the ICARO-2 study

Author

Andrea Zini, Tiziana Tassinari, Alessandro Pezzini, Domenico Consoli, Paolo Frigio Nichelli, Domenico Inzitari, Alessandro Padovani, Giorgio Silvestrelli, Giovanni Orlandi, Alberto Chiti, Serena Monaco, Mascia Nesi, Simona Marcheselli, Danilo Toni, Alessio Pieroni, Gino Gialdini, Carlo Ferrarese, Michele Venti, Alfonso Ciccone, Giampiero Galletti, Caso, M. Del Sette, Manuel Cappellari, Michele Augusto Riva, Mauro Silvestrini, Raffaella Cerqua, M. L. Delodovici, Claudia Trentini, Rossana Tassi, Elisabetta Traverso, P Bovi, Emilio Luda, Patrizia Nencini, Paolo Previdi, Giancarlo Agnelli, Maurizio Paciaroni, Giorgio Bono, Alessia Lanari, Andrea Alberti, Simone Beretta, Cataldo D'Amore, Monica Acciarresi, Giuseppe Martini, Paciaroni, M, Agnelli, G, Caso, V, Pieroni, A, Bovi, P, Cappellari, M, Zini, A, Nichelli, P, Inzitari, D, Nesi, M, Nencini, P, Pezzini, A, Padovani, A, Tassinari, T, Orlandi, G, Chiti, A, Gialdini, G, Alberti, A, Venti, M, Acciarresi, M, D'Amore, C, Luda, E, Tassi, R, Martini, G, Ferrarese, C, Beretta, S, Trentini, C, Silvestrelli, G, Lanari, A, Previdi, P, Ciccone, A, Delodovici, M, Bono, G, Galletti, G, Marcheselli, S, Del Sette, M, Traverso, E, Riva, M, Silvestrini, M, Cerqua, R, Consoli, D, Monaco, S, and Toni, D

Subjects
Carotid Artery Diseases, Male, Neurology, patent foramen ovale, medicine.medical_treatment, stroke, trombolysis ischemic, Tissue plasminogen activator, Brain Ischemia, Brain ischemia, Cohort Studies, Systemic thrombolysis, Outcome Assessment, Health Care, Occlusion, 80 and over, Acute stroke, Multicenter Studies as Topic, Thrombolytic Therapy, carotid occlusion, acute stroke, systemic thrombolysis, outcome, Stroke, Carotid occlusion, Outcome, Aged, 80 and over, Fibrinolytic Agent, Thrombolysis, Middle Aged, Administration, Intravenous, Aged, Case-Control Studies, Female, Fibrinolytic Agents, Humans, Outcome Assessment (Health Care), Tissue Plasminogen Activator, Treatment Outcome, Neurology (clinical), Cardiology and Cardiovascular Medicine, Administration, Cardiology, Internal carotid artery, Case-Control Studie, Intravenous, Human, medicine.drug, medicine.medical_specialty, Intravenous thrombolysis, education, Administration, Intravenou, Systemic thrombolysi, Carotid Artery Occlusion, Internal medicine, medicine.artery, medicine, cardiovascular diseases, Carotid Artery Disease, business.industry, medicine.disease, Acute Ischemic Stroke, Cohort Studie, business, Fibrinolytic agent
Abstract

Background and Purposes: In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion. Methods: Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke – International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3–6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time. Results: A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0–1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9–11.1) and mortality or disability (OR 5.0; 95% CI 2.9–8.7) at 90 days. Conclusions: This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome.

Published
2012

23. Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study

Author

Federica Macellari, Simone Beretta, Mauro Silvestrini, Andrew M. Demchuk, Michele Venti, Danilo Toni, Charlotte Cordonnier, Mascia Nesi, Claudia Trentini, Giovanni Orlandi, Paolo Bovi, Renganayaki Pandurengan, Alessia Lanari, Andrea Alberti, Ioannis Heliopoulos, Rossana Tassi, Simona Marcheselli, Frédéric Dumont, Antonio Baldi, Alessandro Padovani, Serena Monaco, Charitomeni Piperidou, Giuseppe Martini, James C. Grotta, Didier Leys, Elisabetta Traverso, Carlo Ferrarese, Edoardo Donati, Maurizio Paciaroni, Alessandro Pezzini, Valeria Caso, Emilio Luda, Sung Il Sohn, Giorgio Silvestrelli, Francesco Corea, Clotilde Balucani, Simerpreet Bal, Patrizia Nencini, Jessica Kepplinger, Manuel Cappellari, Farhaan S Vahidy, Monica Acciarresi, Cataldo D'Amore, Stéphanie Debette, Andrei V. Alexandrov, Ulf Bodechtel, Nicole R. Gonzales, Melvin R Sline, Paolo Previdi, Sebastiano D'Anna, Domenico Consoli, Domenico Inzitari, Gino Gialdini, Maria Luisa DeLodovici, Alberto Chiti, Massimo Del Sette, Giampiero Galletti, Giancarlo Agnelli, Paolo Invernizzi, Giorgio Bono, Georgios Tsivgoulis, Kristian Barlinn, Raffaella Cerqua, Luisa Fofi, Paciaroni, M, Balucani, C, Agnelli, G, Caso, V, Silvestrelli, G, Grotta, J, Demchuk, A, Sohn, S, Orlandi, G, Leys, D, Pezzini, A, Alexandrov, A, Silvestrini, M, Fofi, L, Barlinn, K, Inzitari, D, Ferrarese, C, Tassi, R, Tsivgoulis, G, Consoli, D, Baldi, A, Bovi, P, Luda, E, Galletti, G, Invernizzi, P, Delodovici, M, Corea, F, Del Sette, M, Monaco, S, Marcheselli, S, Alberti, A, Venti, M, Acciarresi, M, D'Amore, C, Macellari, F, Lanari, A, Previdi, P, Gonzales, N, Pandurengan, R, Vahidy, F, Sline, M, Bal, S, Chiti, A, Gialdini, G, Dumont, F, Cordonnier, C, Debette, S, Padovani, A, Cerqua, R, Bodechtel, U, Kepplinger, J, Nesi, M, Nencini, P, Beretta, S, Trentini, C, Martini, G, Piperidou, C, Heliopoulos, I, D'Anna, S, Cappellari, M, Donati, E, Bono, G, Traverso, E, and Toni, D

Subjects
Male, medicine.medical_specialty, acute stroke, carotid occlusion, outcome, thrombolysis, Time Factors, medicine.medical_treatment, acute stroke carotid occlusion outcome thrombolysis, Tissue plasminogen activator, Brain Ischemia, Fibrinolytic Agents, Modified Rankin Scale, Internal medicine, medicine.artery, Occlusion, 80 and over, medicine, Humans, Carotid Stenosis, Thrombolytic Therapy, Stroke, Aged, Advanced and Specialized Nursing, Aged, 80 and over, Case-Control Studies, Female, Middle Aged, Tissue Plasminogen Activator, Treatment Outcome, Carotid Artery, Internal, Neurology (clinical), Cardiology and Cardiovascular Medicine, business.industry, Thrombolysis, medicine.disease, Internal, Surgery, acute stroke, carotid occlusion, outcome, thrombolysis, Cardiology, Carotid Artery, Internal carotid artery, business, Plasminogen activator, Fibrinolytic agent, medicine.drug
Abstract

Background and Purpose— The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods— ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0–2) or unfavorable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Results— Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03–3.15; P =0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36–3.22; P =0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87–58.71; P =0.068) in the cases than in the controls. Conclusions— In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.

Published
2012

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