George Ntaios, Konstantinos Vemmos, Gregory Y.H. Lip, Elena Koroboki, Efstathios Manios, Anastasia Vemmou, Ana Rodríguez Campello, Valentina Arnao,
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1 George Ntaios, Konstantinos Vemmos, Gregory Y.H. Lip, Elena Koroboki, Efstathios Manios, Anastasia Vemmou, Ana Rodríguez Campello, Valentina Arnao, Valeria Caso, Maurizio Paciaroni, Exuperio Diez-Tejedor,, Blanca Fuentes, Josefa Pérez Lucas, Antonio Arauz, Sebastian F. Ameriso, Maximiliano A. Hawkes, Lucía Pertierra, Maia Gómez-Schneider, Fabio Bandini, Beatriz Chavarria Cano, Ana Maria Iglesias Mohedano, Andrés García Pastor, Antonio Gil-Núñez, Jukka Putaala, Turgut Tatlisumak, Miguel A. Barboza, George Athanasakis, Konstantinos Makaritsis, Vasileios Papavasileiou
2 George Ntaios Larissa University Hospital,Greece Konstantinos Vemmos Gregory Y.H. Lip Elena Koroboki Efstathios Manios Anastasia Vemmou Ana Rodríguez Campello Valentina Arnao Valeria Caso Maurizio Paciaroni Exuperio Diez-Tejedor Blanca Fuentes Josefa Pérez Lucas Antonio Arauz Medical School of Athens, Alexandra Hospital University of Birmingham, UK Medical School of Athens, Alexandra Hospital Medical School of Athens, Alexandra Hospital Medical School of Athens, Alexandra Hospital Universitat Autònoma de Barcelona, Spain Stroke Unit, University of Perugia, Italy Stroke Unit, University of Perugia, Italy Stroke Unit, University of Perugia, Italy Autónoma University of Madrid, Spain Autónoma University of Madrid, Spain Autónoma University of Madrid, Spain Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez Mexico. Sebastian F. Ameriso Institute for Neurological Research, FLENI, Buenos Aires, Argentina
3 Maximiliano A. Hawkes Institute for Neurological Research, FLENI, Buenos Aires, Argentina Lucía Pertierra Maia Gómez-Schneider Fabio Bandini Beatriz Chavarria Cano Ana Maria Iglesias Mohedano Andrés García Pastor Antonio Gil-Núñez Jukka Putaala Turgut Tatlisumak Miguel A. Barboza George Athanasakis Konstantinos Makaritsis Vasileios Papavasileiou Institute for Neurological Research, FLENI, Buenos Aires, Argentina Institute for Neurological Research, FLENI, Buenos Aires, Argentina S. Paolo Hospital, Savona, Italy Universidad Complutense de Madrid, Spain Universidad Complutense de Madrid, Spain Universidad Complutense de Madrid, Spain Universidad Complutense de Madrid, Spain Helsinki university Central Hospital and University of Helsinki, Finland Helsinki university Central Hospital and University of Helsinki,Finland Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden Hospital Dr. Rafael A. Calderón Guardia, CCSS. University of Costa Rica Larissa University Hospital, Greece Larissa University Hospital, Greece Larissa University Hospital, Greece Manchester Academic Health Sciences Centre, Salford Royal Foundation Trust,UK
4 ESUS: Embolic Stroke of Undetermined Source Hart et al. Lancet Neurol 2014; 13:
5 ESUS diagnostic criteria Non-lacunar brain infarct on the brain CT or MRI No extracranial or intracranial atherosclerosis causing 50% luminal stenosis in arteries supplying the area of ischemia No major-risk cardioembolic source No any other specific cause of stroke (e.g. arteritis, dissection, migraine/vasospasm, drug misuse).
6 CHADS₂ and CHA₂DS₂-VASc Congestive Heart Failure 1 point Hypertension 1 point Age 75 years 1 point Diabetes Mellitus 1 point Stroke or TIA 2 points Congestive Heart Failure Hypertension Age 75 years Diabetes Mellitus Stroke or TIA or thromboembolism Vascular Disease Age years old Sex(Female) 1 point 1 point 2 points 1 point 2 points 1 point 1 point 1 point
7 Aim of the study CHADS₂ and CHA₂DS₂-VASc scores independent risk factors for recurrence or death?
8 Participating countries
9 Methods Pre-stroke CHADS 2 and CHA 2 DS 2 -VASc scores
10 Categorization and analysis of CHADS 2 a) CHADS 2 =0 CHADS 2 =1 CHADS 2 =2 CHADS 2 =3 CHADS 2 =4 CHADS 2 =5 CHADS 2 =6 b) CHADS 2 =0 CHADS 2 =1 CHADS 2 =2 CHADS 2 =3 CHADS 2 =4 CHADS 2 =5 CHADS 2 =6
11 Categorization and analysis of CHA₂DS₂-VASc a)according to the risk for the Males CHA 2 DS 2 -VASc Low risk Intermediate risk High risk b)according to the risk for the Females Low risk Intermediate risk CHA 2 DS 2 -VASc c) High risk CHA 2 DS 2 -VASc d) CHA 2 DS 2 -VASc
12 Statistical Analysis Univariate and Multivariate Cox-regression analysis Kaplan-Meier product limit method
13 Results Parameter ESUS(n=1095) Demographics Female gender 449(41.0%) Age(years) 68.0( ) Comorbidities-risk factors Pre-stroke mrs (95.4%) Hypertension 649 (59.3%) Diabetes mellitus 217 (19.8%) Smoking (current or ex) 386 (35.3%) Previous stroke or TIA 131 (12.0%) Heart failure 80 (7.3%) Dyslipidemia 487 (44.5%) Coronary artery disease 167 (15.3%) Peripheral artery disease 49 (4.5%) Previous thromboembolism 16 (1.5%)
14 Results Parameter ESUS(n=1095) NIHSS score 5 (2-10) Follow-up (months) 31 (14-59) Acute treatment Antiplatelets only 915 (83.6%) Intravenous thrombolysis 165 (15.1%) Acute endovascular (pure) 6 (0.5%) Bridging 8 (0.7%) Other acute recanalization 1 (0.1%) Treatment on discharge No antithrombotic 11 (1.0%) Antiplatelet(s) 937 (87.4%) Oral anticoagulant 103 (9.6%) Antiplatelet(s) and oral anticoagulant 21 (2.0%)
15 Frequency distribution and event rates for ischemic stroke / TIA recurrence and mortality for CHADS₂ scores strata
16 Frequency distribution and event rates for ischemic stroke / TIA recurrence and mortality for CHA₂DS₂-VASc scores strata
17 Cox-regression analyses of the association between the pre-stroke CHADS₂ and CHA₂DS₂-VASc scores and ischemic stroke/tia recurrence. Associations are presented as hazard ratios and 95% confidence intervals.
18 Cox-regression analyses of the association between the pre-stroke CHADS₂ and CHA₂DS₂-VASc scores and mortality. Associations are presented as hazard ratios and 95% confidence intervals.
19 Cumulative probability of recurrent ischemic stroke/tia and death in ESUS patients according to the pre-stroke CHADS₂.
20 Cumulative probability of recurrent ischemic stroke/tia and death in ESUS patients according to the pre-stroke CHA₂DS₂-VASc score.
21 Cumulative probability of recurrent ischemic stroke/tia and death in ESUS patients according to the pre-stroke CHA₂DS₂-VASc score.
22 Cumulative probability of recurrent ischemic stroke/tia and death in ESUS patients according to the pre-stroke CHA₂DS₂-VASc score.
23 Discussion Strengths of the analysis: >1000 patients from 11 stroke registries Long mean follow-up Standardized definition of ESUS Different categorization of the 2 scores On the other hand, it includes any inherent limitations of any retrospective multicenter analysis
24 Take-Home messages CHADS₂ and CHA₂DS₂-VASc scores are independently associated with the risk of ischemic stroke/tia recurrence and death in ESUS patients The risk of stroke recurrence and death in patients with a CHA₂DS₂-VASc score 2 is much higher compared to patients with a score of 0
An international, double-blind, phase III randomized trial. Main Results
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