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Stroke. 2019 Aug;50(8):2168-2174. doi: 10.1161/STROKEAHA.119.025350. Epub 2019 Jun 25.

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 information

1
From the Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Italy (M. Paciaroni, G.A., V.C., M.A., A.A., M.V., M.G.M., M.C.V., P.P., M.G.).
2
S.C. di Neurologia e S.S. di Stroke Unit, ASST di Mantova, Italy (G.S., A.C.).
3
University Center for Medicine of Aging and Rehabilitation, University of Basel, Felix-Platter Hospital, Switzerland (D.J.S., S.E., G.M.D.M., A. Polymeris).
4
Neurology Unit, Stroke Unit, Istituto di Ricovero e Cura a Carattere Scientifico, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (M.L.Z.).
5
New York University Langone Health (S.Y.).
6
Département des Neurosciences Cliniques Centre Hopitalier Universitaire Vaudois, Centre Cérébrovasculaire, Service de Neurologie, Lausanne, Switzerland (P.M., A.E.).
7
Department of Neurology, Bogomolets National Medical University, Kyiv, Ukraine (K.A.).
8
Department of Neurology, Keimyung University School of Medicine, Daegu, South Korea (S.I.S.).
9
Struttura Semplice Ospedaliera Stroke Unit, Unità Organica Neurologia, DAI di Neuroscienze, Azienda Ospedaliera Universitaria Integrata, Verona, Italy (M.C., B.B.).
10
Stroke Unit, Department of Neurology, Santa Corona Hospital, Pietra Ligure, Savona, Italy (T.T., V.S.).
11
Stroke Unit, AOU Senese, Siena, Italy (R.T., F.G., M.A., G.M.).
12
Internal Medicine, San Giuseppe Hospital, Empoli, Italy (L.M., E. Grifoni).
13
Department of Neurology, University Hospital of Ioannina, Greece (A.H.K., S.G.).
14
U.O. Neurologia Presidio Ospedaliero di Ravenna Azienda USL della Romagna, Italy (E.M.L., M. Padroni).
15
Department of Medicine, University of Thessaly, Larissa, Greece (G.N., E.K., K.P., K.M.).
16
Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.).
17
Stroke Unit, Ospedale Civico, Palermo, Italy (S.M., M. Mannino).
18
Department of Neurology, Saarland University Medical Center, Homburg, Germany (P.L.).
19
Department of Neurology, Ospedale San Paolo, Savona, Italy (F.B.).
20
Second Department of Neurology, Attikon Hospital, National and Kapodistrian University of Athens, School of Medicine, Greece (C.L., L.P., G.T.).
21
Medical School and Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., K.L.).
22
Clinica Neurologica-Azienda Ospedaliero-Universitaria, Pisa, Italy (M. Mancuso, M. Maccarrone, L.U., N.G., E.F.).
23
Neurology, L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Italy (L.P., S.R., P.B.).
24
Department of Medicine and Surgery, University of Insubria, Ospedale di Circolo Varese, Italy (S.G., W.A.).
25
Division of Cardiology, University of Torino, Città della Salute e della Scienza Hospital, Italy (E.T., F.A.).
26
Neurologia, Ospedale Apuano, Massa Carrara, Italy (A.C., G.O.).
27
Stroke Unit, Dipartimento Geriatrico Riabilitativo, University of Parma, Italy (L.D.).
28
Stroke and Neurorehabilitation Unit, MC Universal Clinic Oberig, Kyiv, Ukraine (Y.F.).
29
Neurologia d'urgenza e Stroke Unit, Istituto Clinico Humanitas, Rozzano, Milano, Italy (S.M.).
30
Department of Internal Medicine, Magenta Hospital, Italy (N.M., A.R., E.V.).
31
Struttura Complessa di Neurologia, Ente Ospedaliero Ospedali Galliera, Genoa, Italy (E.S., M.D.S.).
32
Internist-Intensive Care Specialist, Intensive Care Unit, General Hospital of Larissa, Greece (P.P., A.K.).
33
Clinic of Neurology, Clinical Center Vojvodina, University of Novi Sad, Serbia (N.P., M.Z.).
34
Stroke Unit, Department of Systems Medicine, University of Tor Vergata, Rome, Italy (A.R., M.D.).
35
Stroke Unit, Department of Neurology, Sant'Andrea Hospital, La Spezia, Italy (E. Giorli).
36
Division of Stroke and Cerebrovascular Diseases, Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (B.C.M.G., K.L.F.).
37
Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Italy (A. Pezzini).
38
Municipal Budgetary Healthcare Institution of Novosibirsk, City Clinical Hospital No. 1, Novosibirsk State Medical University, Russia (B.D., V.V.).
39
Stroke Unit, Ospedale di Portogruaro, Venice, Italy (A.B., C.D.).
40
Neurology, Hamad Medical Corporation, Doha, Qatar (D.D.).
41
Unità Organica Gravi Cerebrolesioni, San Giovanni Battista Hospital, Foligno, Italy (F.C.).
42
Department of Neurology, Helsinki University Hospital, Finland (J.P.).
43
Neurologia, Ospedale Piemonte, Istituto di Ricovero e Cura a Carattere Scientifico Bonino Pulejo, Messina, Italy (P.S.).
44
Neurologia, Ospedale di Macerata, Italy (K.N.).
45
Department of Neurology and Psychiatry, Sapienza University of Rome, Italy (A.R., D.T.).
46
Department of Neurology, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece (G.T.).
47
Department of Neurology, University of Tennessee Health Science Center, Memphis (G.T.).

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.

KEYWORDS:

atrial fibrillation; humans; prevention and control; risk factors; stroke

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