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

George Ntaios Larissa University Hospital ,Greece

Konstantinos Vemmos Medical School of Athens, Alexandra Hospital

Gregory Y.H. Lip University of Birmingham, UK

Elena Koroboki Medical School of Athens, Alexandra Hospital

Efstathios Manios Medical School of Athens, Alexandra Hospital

Anastasia Vemmou Medical School of Athens, Alexandra Hospital

Ana Rodríguez Campello Universitat Autònoma de Barcelona, Spain

Valentina Arnao Stroke Unit, University of Perugia, Italy

Valeria Caso Stroke Unit, University of Perugia, Italy

Maurizio Paciaroni Stroke Unit, University of Perugia, Italy

Exuperio Diez-Tejedor Autónoma University of Madrid, Spain

Blanca Fuentes Autónoma University of Madrid, Spain

Josefa Pérez Lucas Autónoma University of Madrid, Spain

Antonio Arauz

Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez Mexico.

Sebastian F. Ameriso

Institute for Neurological Research “, FLENI, Buenos Aires, Argentina

Maximiliano A. Hawkes Institute for Neurological Research “, FLENI, Buenos Aires, Argentina

Lucía Pertierra Institute for Neurological Research “, FLENI, Buenos Aires, Argentina

Maia Gómez-Schneider Institute for Neurological Research “, FLENI, Buenos Aires, Argentina

Fabio Bandini S. Paolo Hospital, Savona, Italy

Beatriz Chavarria Cano Universidad Complutense de Madrid, Spain

Ana Maria Iglesias Mohedano Universidad Complutense de Madrid, Spain

Andrés García Pastor Universidad Complutense de Madrid, Spain

Antonio Gil-Núñez Universidad Complutense de Madrid, Spain

Jukka Putaala Helsinki university Central Hospital and University of Helsinki, Finland

Turgut Tatlisumak Helsinki university Central Hospital and University of Helsinki,Finland Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden

Miguel A. Barboza Hospital Dr. Rafael A. Calderón Guardia, CCSS. University of Costa Rica

George Athanasakis Larissa University Hospital, Greece

Konstantinos Makaritsis Larissa University Hospital, Greece

Vasileios Papavasileiou Larissa University Hospital, Greece Manchester Academic Health Sciences Centre, Salford Royal Foundation Trust,UK

ESUS: Embolic Stroke of Undetermined Source

Hart et al. Lancet Neurol 2014; 13: 429–38

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).

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 1 point

Hypertension 1 point

Age≥75 years 2 points

Diabetes Mellitus 1 point

Stroke or TIA or thromboembolism 2 points

Vascular Disease 1 point

Age 65-74 years old 1 point

Sex(Female) 1 point

Aim of the study

CHADS₂ and CHA₂DS₂-VASc scores independent risk factors for recurrence or death?

Participating countries

Methods

Pre-stroke CHADS2 and CHA2DS2-VASc scores

Categorization and analysis of CHADS2

CHADS2=0 CHADS2=1

CHADS2=2

CHADS2=3

CHADS2=4

CHADS2=5

CHADS2=6

CHADS2=0 CHADS2=1

CHADS2=2

CHADS2=3

CHADS2=4

CHADS2=5

CHADS2=6

a)

b)

Categorization and analysis of CHA₂DS₂-VASc

0 1 2 3 4 5 6 7 8

CHA2DS2-VASc

0 1 2 3 4 5 6 7 8

0 1 2 3 4 5 6 7 8

0 1 2 3 4 5 6 7 8

CHA2DS2-VASc

CHA2DS2-VASc

CHA2DS2-VASc

Low risk Intermediate risk High risk

a)According to the risk for the Males

Low risk Intermediate risk High risk

b)According to the risk for the Females

c)

d)

Statistical Analysis

Univariate and Multivariate Cox-regression analysis

Kaplan-Meier product limit method

Results Parameter ESUS(n=1095)

Demographics

Female gender 449(41.0%)

Age(years) 68.0(54.0-77.0)

Comorbidities-risk factors

Pre-stroke mRS≤2 1036 (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%)

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%)

Frequency distribution and event rates for ischemic stroke / TIA recurrence and mortality for CHADS₂ scores’ strata

Frequency distribution and event rates for ischemic stroke / TIA recurrence and mortality for CHA₂DS₂-VASc scores’ strata

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.

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.

Cumulative probability of recurrent ischemic stroke/TIA and death in ESUS patients according to the pre-stroke CHADS₂.

Cumulative probability of recurrent ischemic stroke/TIA and death in ESUS patients according to the pre-stroke CHA₂DS₂-VASc score.

Cumulative probability of recurrent ischemic stroke/TIA and death in ESUS patients according to the pre-stroke CHA₂DS₂-VASc score.

Cumulative probability of recurrent ischemic stroke/TIA and death in ESUS patients according to the pre-stroke CHA₂DS₂-VASc score.

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

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