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

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