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

Maurizio Paciaroni, MD; Giancarlo Agnelli, MD; Valeria Caso, PhD; Giorgio Silvestrelli, PhD; David Julian Seiffge, MD; Stefan Engelter, MD; Gian Marco De Marchis; MD MSc; Alexandros Polymeris, MD; Maria Luisa Zedde, MD; Shadi Yaghi, MD; Patrik Michel, MD; Ashraf Eskandari, MD; Kateryna Antonenko, MD; Sung-Il Sohn, MD; Manuel Cappellari, MD; Tiziana Tassinari, MD; Rossana Tassi, MD; Luca Masotti, MD; Aristeidis H. Katsanos, MD; Sotirios Giannopoulos, MD; Monica Acciarresi, MD; Andrea Alberti, MD; Michele Venti, PhD; Maria Giulia Mosconi, MD; Maria Cristina Vedovati, MD; Patrizia Pierini, MD; Michela Giustozzi, MD; Enrico Maria Lotti, MD; George Ntaios, MD; Odysseas Kargiotis, MD; Serena Monaco, MD; Piergiorgio Lochner, MD; Fabio Bandini, MD; Chrysoula Liantinioti, MD; Lina Palaiodimou, MD; Azmil H. Abdul-Rahim, MD; Kennedy Lees, MD; Michelangelo Mancuso, MD; Leonardo Pantoni, MD; Silvia Rosa, MD; Pierluigi Bertora, MD; Silvia Galliazzo, MD; Walter Ageno, MD; Elisabetta Toso, MD; Filippo Angelini, MD; Alberto Chiti, MD; Giovanni Orlandi, MD; Licia Denti, MD; Yuriy Flomin, MD; Simona Marcheselli, MD; Nicola Mumoli, MD; Alexandra Rimoldi, MD; Elena Verrengia, MD; Erika Schirinzi, MD; Massimo Del Sette, MD; Panagiotis Papamichalis, MD; Apostolos Komnos, MD; Nemanja Popovic, MD; Marija Zarkov, MD; Alessandro Rocco, MD; Marina Diomedi, MD; Elisa Giorli, MD; Alfonso Ciccone, MD; Brian C. Mac Grory, MD; Karen L. Furie, MD; Bruno Bonetti, MD; Valentina Saia, MD; Francesca Guideri, MD; Maurizio Acampa, MD; Giuseppe Martini, MD; Elisa Grifoni, MD; Marina Padroni, MD; Efstathia Karagkiozi, MD; Kalliopi Perlepe, MD; Konstantinos Makaritsis, MD; Marina Mannino, MD; Miriam Maccarrone, MD; Leonardo Ulivi, MD; Nicola Giannini, MD; Elena Ferrari, MD; Alessandro Pezzini, MD; Boris Doronin, MD; Vera Volodina, MD; Antonio Baldi, MD; Cataldo D’Amore, MD; Dirk Deleu, MD; Francesco Corea, MD; Jukka Putaala, MD; Paola Santalucia, MD; Katiuscia Nardi, MD; Angela Risitano; Danilo Toni; Georgios Tsivgoulis, MD

doi:10.1161/STROKEAHA.119.025350

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 CHA2DS2-VASc score (OR, 1.72 for each point increase; 95% CI, 1.58–1.88) were associated with ischemic events. Among the CHA2DS2-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 CHA2DS2-VASc score were associated with increased risk of cerebrovascular events.

Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention. The RENo Study / Md, Maurizio Paciaroni; Md, Giancarlo Agnelli; Phd, Valeria Caso; Phd, Giorgio Silvestrelli; Md, David Julian Seiffge; Md, Stefan Engelter; Marco De Marchis, Gian; Msc, Md; Md, Alexandros Polymeris; Md, Maria Luisa Zedde; Md, Shadi Yaghi; Md, Patrik Michel; Md, Ashraf Eskandari; Md, Kateryna Antonenko; Md, Sung-Il Sohn; Md, Manuel Cappellari; Md, Tiziana Tassinari; Md, Rossana Tassi; Md, Luca Masotti; Md, Aristeidis H. Katsanos; Md, Sotirios Giannopoulos; Md, Monica Acciarresi; Md, Andrea Alberti; Phd, Michele Venti; Md, Maria Giulia Mosconi; Md, Maria Cristina Vedovati; Md, Patrizia Pierini; Md, Michela Giustozzi; Md, Enrico Maria Lotti; Md, George Ntaios; Md, Odysseas Kargiotis; Md, Serena Monaco; Md, Piergiorgio Lochner; Md, Fabio Bandini; Md, Chrysoula Liantinioti; Md, Lina Palaiodimou; Md, Azmil H. Abdul-Rahim; Md, Kennedy Lees; Md, Michelangelo Mancuso; Md, Leonardo Pantoni; Md, Silvia Rosa; Md, Pierluigi Bertora; Md, Silvia Galliazzo; Md, Walter Ageno; Md, Elisabetta Toso; Md, Filippo Angelini; Md, Alberto Chiti; Md, Giovanni Orlandi; Md, Licia Denti; Md, Yuriy Flomin; Md, Simona Marcheselli; Md, Nicola Mumoli; Md, Alexandra Rimoldi; Md, Elena Verrengia; Md, Erika Schirinzi; Md, Massimo Del Sette; Md, Panagiotis Papamichalis; Md, Apostolos Komnos; Md, Nemanja Popovic; Md, Marija Zarkov; Md, Alessandro Rocco; Md, Marina Diomedi; Md, Elisa Giorli; Md, Alfonso Ciccone; Md, Brian C. Mac Grory; Md, Karen L. Furie; Md, Bruno Bonetti; Md, Valentina Saia; Md, Francesca Guideri; Md, Maurizio Acampa; Md, Giuseppe Martini; Md, Elisa Grifoni; Md, Marina Padroni; Md, Efstathia Karagkiozi; Md, Kalliopi Perlepe; Md, Konstantinos Makaritsis; Md, Marina Mannino; Md, Miriam Maccarrone; Md, Leonardo Ulivi; Md, Nicola Giannini; Md, Elena Ferrari; Md, Alessandro Pezzini; Md, Boris Doronin; Md, Vera Volodina; Md, Antonio Baldi; Md, Cataldo D’Amore; Md, Dirk Deleu; Md, Francesco Corea; Md, Jukka Putaala; Md, Paola Santalucia; Md, Katiuscia Nardi; Risitano, Angela; Toni, Danilo; Md, Georgios Tsivgoulis. - In: STROKE. - ISSN 0039-2499. - 50:8(2019), pp. 2168-2174. [10.1161/STROKEAHA.119.025350]

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

Maurizio Paciaroni, MD;Giancarlo Agnelli, MD;Valeria Caso, PhD;Giorgio Silvestrelli, PhD;David Julian Seiffge, MD;Stefan Engelter, MD;Gian Marco De Marchis;MD MSc;Alexandros Polymeris, MD;Maria Luisa Zedde, MD;Shadi Yaghi, MD;Patrik Michel, MD;Ashraf Eskandari, MD;Kateryna Antonenko, MD;Sung-Il Sohn, MD;Manuel Cappellari, MD;Tiziana Tassinari, MD;Rossana Tassi, MD;Luca Masotti, MD;Aristeidis H. Katsanos, MD;Sotirios Giannopoulos, MD;Monica Acciarresi, MD;Andrea Alberti, MD;Michele Venti, PhD;Maria Giulia Mosconi, MD;Maria Cristina Vedovati, MD;Patrizia Pierini, MD;Michela Giustozzi, MD;Enrico Maria Lotti, MD;George Ntaios, MD;Odysseas Kargiotis, MD;Serena Monaco, MD;Piergiorgio Lochner, MD;Fabio Bandini, MD;Chrysoula Liantinioti, MD;Lina Palaiodimou, MD;Azmil H. Abdul-Rahim, MD;Kennedy Lees, MD;Michelangelo Mancuso, MD;Leonardo Pantoni, MD;Silvia Rosa, MD;Pierluigi Bertora, MD;Silvia Galliazzo, MD;Walter Ageno, MD;Elisabetta Toso, MD;Filippo Angelini, MD;Alberto Chiti, MD;Giovanni Orlandi, MD;Licia Denti, MD;Yuriy Flomin, MD;Simona Marcheselli, MD;Nicola Mumoli, MD;Alexandra Rimoldi, MD;Elena Verrengia, MD;Erika Schirinzi, MD;Massimo Del Sette, MD;Panagiotis Papamichalis, MD;Apostolos Komnos, MD;Nemanja Popovic, MD;Marija Zarkov, MD;Alessandro Rocco, MD;Marina Diomedi, MD;Elisa Giorli, MD;Alfonso Ciccone, MD;Brian C. Mac Grory, MD;Karen L. Furie, MD;Bruno Bonetti, MD;Valentina Saia, MD;Francesca Guideri, MD;Maurizio Acampa, MD;Giuseppe Martini, MD;Elisa Grifoni, MD;Marina Padroni, MD;Efstathia Karagkiozi, MD;Kalliopi Perlepe, MD;Konstantinos Makaritsis, MD;Marina Mannino, MD;Miriam Maccarrone, MD;Leonardo Ulivi, MD;Nicola Giannini, MD;Elena Ferrari, MD;Alessandro Pezzini, MD;Boris Doronin, MD;Vera Volodina, MD;Antonio Baldi, MD;Cataldo D’Amore, MD;Dirk Deleu, MD;Francesco Corea, MD;Jukka Putaala, MD;Paola Santalucia, MD;Katiuscia Nardi, MD;Angela Risitano;Danilo Toni;Georgios Tsivgoulis, MD

2019

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 CHA2DS2-VASc score (OR, 1.72 for each point increase; 95% CI, 1.58–1.88) were associated with ischemic events. Among the CHA2DS2-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 CHA2DS2-VASc score were associated with increased risk of cerebrovascular events.

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	Anno di pubblicazione
	
				2019
			
	Parole chiave
	
				atrial fibrillation; humans; prevention and control; risk factors; stroke
			
	Tipologia
	
				01 Pubblicazione su rivista::01a Articolo in rivista
			
	Citazione
	
				Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention. The RENo Study / Md, Maurizio Paciaroni; Md, Giancarlo Agnelli; Phd, Valeria Caso; Phd, Giorgio Silvestrelli; Md, David Julian Seiffge; Md, Stefan Engelter; Marco De Marchis, Gian; Msc, Md; Md, Alexandros Polymeris; Md, Maria Luisa Zedde; Md, Shadi Yaghi; Md, Patrik Michel; Md, Ashraf Eskandari; Md, Kateryna Antonenko; Md, Sung-Il Sohn; Md, Manuel Cappellari; Md, Tiziana Tassinari; Md, Rossana Tassi; Md, Luca Masotti; Md, Aristeidis H. Katsanos; Md, Sotirios Giannopoulos; Md, Monica Acciarresi; Md, Andrea Alberti; Phd, Michele Venti; Md, Maria Giulia Mosconi; Md, Maria Cristina Vedovati; Md, Patrizia Pierini; Md, Michela Giustozzi; Md, Enrico Maria Lotti; Md, George Ntaios; Md, Odysseas Kargiotis; Md, Serena Monaco; Md, Piergiorgio Lochner; Md, Fabio Bandini; Md, Chrysoula Liantinioti; Md, Lina Palaiodimou; Md, Azmil H. Abdul-Rahim; Md, Kennedy Lees; Md, Michelangelo Mancuso; Md, Leonardo Pantoni; Md, Silvia Rosa; Md, Pierluigi Bertora; Md, Silvia Galliazzo; Md, Walter Ageno; Md, Elisabetta Toso; Md, Filippo Angelini; Md, Alberto Chiti; Md, Giovanni Orlandi; Md, Licia Denti; Md, Yuriy Flomin; Md, Simona Marcheselli; Md, Nicola Mumoli; Md, Alexandra Rimoldi; Md, Elena Verrengia; Md, Erika Schirinzi; Md, Massimo Del Sette; Md, Panagiotis Papamichalis; Md, Apostolos Komnos; Md, Nemanja Popovic; Md, Marija Zarkov; Md, Alessandro Rocco; Md, Marina Diomedi; Md, Elisa Giorli; Md, Alfonso Ciccone; Md, Brian C. Mac Grory; Md, Karen L. Furie; Md, Bruno Bonetti; Md, Valentina Saia; Md, Francesca Guideri; Md, Maurizio Acampa; Md, Giuseppe Martini; Md, Elisa Grifoni; Md, Marina Padroni; Md, Efstathia Karagkiozi; Md, Kalliopi Perlepe; Md, Konstantinos Makaritsis; Md, Marina Mannino; Md, Miriam Maccarrone; Md, Leonardo Ulivi; Md, Nicola Giannini; Md, Elena Ferrari; Md, Alessandro Pezzini; Md, Boris Doronin; Md, Vera Volodina; Md, Antonio Baldi; Md, Cataldo D’Amore; Md, Dirk Deleu; Md, Francesco Corea; Md, Jukka Putaala; Md, Paola Santalucia; Md, Katiuscia Nardi; Risitano, Angela; Toni, Danilo; Md, Georgios Tsivgoulis. - In: STROKE. - ISSN 0039-2499. - 50:8(2019), pp. 2168-2174. [10.1161/STROKEAHA.119.025350]

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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1404467

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