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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. Subclinical Vascular Brain Lesions in Young Adults With Acute Ischemic Stroke

Author

Valeria De Giuli, Mario Grassi, Michele Besana, Marialuisa Zedde, Andrea Zini, Corrado Lodigiani, Simona Marcheselli, Anna Cavallini, Giuseppe Micieli, Maurizia Rasura, Maria Luisa DeLodovici, Giampaolo Tomelleri, Nicoletta Checcarelli, Alberto Chiti, Elisa Giorli, Massimo Del Sette, Lucia Tancredi, Antonella Toriello, Massimiliano Braga, Andrea Morotti, Debora Pezzini, Martina Locatelli, Valentina Mazzoleni, Sonia Bonacina, Massimo Gamba, Mauro Magoni, Rosalba Patella, Alessandra Spalloni, Anna Maria Simone, Rosario Pascarella, Sandro Beretta, Alessandro Padovani, Roberto Gasparotti, Alessandro Pezzini, Nicola Gilberti, Paola Ferrazzi, Elena Banfi, Luca Librè, Elisabetta Traverso, Erika Schirinzi, Federico Carimati, Manuel Cappellari, Giampiero Locatelli, Laura Demelas, Davide Ferrario, Alessandra Persico, Giovanni Orlandi, Manuela Napoli, Claudio Moratti, and Mario Guidotti

Subjects
Adult, Male, medicine.medical_specialty, Brain Ischemia, Brain ischemia, White matter, Young Adult, Internal medicine, medicine, Humans, Myocardial infarction, Young adult, Stroke, Acute ischemic stroke, Aged, Ischemic Stroke, Subclinical infection, Advanced and Specialized Nursing, business.industry, Brain, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Cerebral Small Vessel Diseases, Cardiology, Brain lesions, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Abstract

Background: Subclinical vascular brain lesions are highly prevalent in elderly patients with stroke. Little is known about predisposing factors and their impact on long-term outcome of patients with stroke at a young age. Methods: We quantified magnetic resonance-defined subclinical vascular brain lesions, including lacunes and white matter hyperintensities, perivascular spaces and cerebral microbleeds, and assessed total small-vessel disease (SVD) score in patients with first-ever acute ischemic stroke aged 18 to 45 years, and followed them up, as part of the multicentre Italian Project on Stroke in Young Adults. The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. We assessed the predictive accuracy of magnetic resonance features and whether the addition of these markers improves outcome prediction over a validated clinical tool, such as the Italian Project on Stroke in Young Adults score. Results: Among 591 patients (males, 53.8%; mean age, 37.5±6.4 years), 117 (19.8%) had subclinical vascular brain lesions. Family history of stroke was associated with lacunes (odds ratio, 2.24 [95% CI, 1.30–3.84]) and total SVD score (odds ratio, 2.06 [95% CI, 1.20–3.53] for score≥1), hypertension with white matter hyperintensities (odds ratio, 2.29 [95% CI, 1.22–4.32]). After a median follow-up of 36.0 months (25th–75th percentile, 38.0), lacunes and total SVD score were associated with primary end point (hazard ratio, 2.13 [95% CI, 1.17–3.90] for lacunes; hazard ratio, 2.17 [95% CI, 1.20–3.90] for total SVD score ≥1), and the secondary end point brain ischemia (hazard ratio, 2.55 [95% CI, 1.36–4.75] for lacunes; hazard ratio, 2.61 [95% CI, 1.42–4.80] for total SVD score ≥1). The predictive performances of the models, including magnetic resonance features were comparable to those of the random model. Adding individual magnetic resonance features to the Italian Project on Stroke in Young Adults score did not improve model prediction. Conclusions: Subclinical vascular brain lesions affect ≈2 in 10 young adults with ischemic stroke. Although lacunes and total SVD score are associated with thrombotic recurrence, they do not improve accuracy of outcome prediction over validated clinical predictors.

Published
2022
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3. 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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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. 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

8. To FAST or Not to FAST: SHOUT-FAST!

Author

Elisa Giorli, Giovanni Orlandi, and Alberto Chiti

Subjects
Advanced and Specialized Nursing, Information retrieval, business.industry, MEDLINE, Medicine, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, medicine.disease, Stroke
Abstract

To the Editor: We read with great interest the article by Kleindorfer et al1 evaluating the effectiveness of FAST and “SUDDENS” message to identify stroke. We agree that FAST may be easier for the lay public to remember, but we have …

Published
2008
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