ARTICLE IN PRESS

Stroke Risk Is Low after Urgently Treated Transient

Ischemic Attack

Thea Vigen, MD,*,† Bente Thommessen, MD, PhD,* and

Ole Morten Rønning, MD, PhD*,†

Background: Over the last decades, the approach to patients with transient isch-
emic attack (TIA) has shifted from treating only patients considered at high risk
of recurrent stroke, to referring all patients with TIA to urgent assessment and
immediate initiation of preventive treatment. The data on how this change has
influenced the stroke rate after TIA are limited. Thus, the primary aim of this
study was to identify the incidence of stroke recurrence after TIA. Second, we
wanted to evaluate the ABCD2 score as a predictor of recurrent stroke. Methods:
Patients discharged with a diagnosis of TIA from the Stroke Unit at Akershus
University Hospital between January 1, 2013 and December 31, 2013 were in-
cluded in the study. Data were obtained from the electronic medical records.
Readmission data to capture recurrent strokes were registered until December 31,
2015. Results: In total, 261 patients were included. Mean age was 70.7 years. Stroke
incidence at 1 month, 1 year, and the end of follow-up was 1.5% (n = 4), 3.4%
(n = 9), and 4.2% (n = 11), respectively. Median time from TIA until recurrent stroke
was 90 days. The ability of the ABCD2 score to predict recurrent stroke was
low. Conclusions: Urgent admission of patients with TIA is followed by a very
low risk of early and late recurrent stroke. The ABCD2 score did not identify
patients at high risk of recurrent stroke. Key Words: Ischemic attack—
transient—emergency—cerebrovascular diseases—recurrent stroke.
© 2017 Published by Elsevier Inc. on behalf of National Stroke Association.

Background of acute stroke treatment is modest, as the narrow treat-

ment window for reperfusion therapy limits its usage.
Cerebrovascular disease is one of the most frequent
However, all patients with stroke can obtain effective sec-
causes of death and disability in the Western world.1 With
ondary prevention, particularly if initiated early after a
an aging population, the human and economic impact
transient ischemic attack (TIA) or stroke, when the risk
of the disease is expected to increase. The effectiveness
of a recurrence is at its highest. Immediate recognition
of a TIA, followed by urgent examination and treat-
From the *Department of Neurology, Medical Division, Akershus
ment, is therefore a prerequisite to reduce the risk of
University Hospital, Lørenskog, Norway; and †Institute of Clinical another stroke.
Medicine, University of Oslo, Oslo, Norway. TIA admission policies have hitherto been influenced
Received May 9, 2017; revision received July 18, 2017; accepted by an underestimation of the risk of early stroke
August 26, 2017.
recurrence2,3 and confidence in the ability of risk predic-
Grant support: This study received grant support from South-
Eastern Norway Regional Health Authority.
tion scores to select high-risk patients. Previous guidelines
Address correspondence to Thea Vigen, MD, Department of have therefore recommended urgent treatment only of
Neurology, Medical Division, Akershus University Hospital, 1478 high-risk patients.4,5 To identify these patients, several clin-
Lørenskog, Norway. E-mail: theav@operamail.com; thea.vigen ical risk prediction scores have been developed, and the
@gmail.com.
ABCD2 score has been the most frequently used.
1052-3057/$ - see front matter
© 2017 Published by Elsevier Inc. on behalf of National Stroke
The policy of urgent treatment only of high-risk pa-
Association. tients has been challenged over the last decade because
https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.08.037 of studies reporting a risk of cardiovascular events after

Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2017: pp ■■–■■ 1
 ARTICLE IN PRESS
2 T. VIGEN ET AL.
TIA of up to 20% per year, with the highest risk within symptoms) were collected from the medical records. Pa-
the first few days after the initial event.6-8 In addition to tients suffering from a stroke during hospitalization for
this, the ability of the ABCD2 score to identify high-risk initial TIA are routinely treated with thrombolysis. To include
patients has been questioned.9 As a result, studies evalu- these patients in the study, the 2013 register for throm-
ating urgent admission of all patients with TIA, regardless bolysis was also reviewed. Definite TIA was defined, based
of ABCD2 score, have been performed. Hospital-based on World Health Organization criteria, as rapidly devel-
studies with fast-track examination of all patients with oped clinical signs of focal or global disturbance of cerebral
TIA have revealed a much lower incidence of recurrent function, including amaurosis fugax, lasting less than 24
cardiovascular events.10-12 In particular, the Express study hours with no apparent nonvascular cause.14 CT and MRI
from 2007 showed a reduction in the 90-day risk of stroke were performed to record any new or old ischemic lesion
recurrence from 10% to 2% after establishing a policy of or cerebral hemorrhage. Patients with transient cerebral
urgent admission of patients with TIA to a stroke clinic.13 symptoms because of cerebral hemorrhage were not in-
New guidelines therefore tend to support urgent admis- cluded in the study. Patients with a probable or possible
sion of all patients with TIA. new ischemic lesion on CT or MRI were not excluded if
Because most studies evaluating stroke recurrence after they met the clinical TIA definition. Atrial fibrillation was
TIA were performed when urgent assessment was not registered when confirmed by electrocardiogram or re-
mandatory, the aim of this study was to obtain real-life ported in the medical history. The Trial of Org 10172 in
data on the risk of recurrent stroke in a Norwegian TIA Acute Stroke Treatment classification was used to deter-
population urgently admitted to an acute stroke unit. In mine TIA etiology.15 Patients with TIA and symptomatic
addition, we wanted to evaluate the ability of the ABCD2 carotid stenosis (≥70% stenosis) had a carotid endarter-
score to predict risk of recurrent stroke after TIA. ectomy as fast as possible during the stay, usually within
4-5 days. Physiological parameters such as blood pres-
sure, heart rate, temperature, and oxygen saturation were
Methods
registered and corrected according to guidelines for acute
The study was conducted at the Stroke Unit, Akershus stroke treatment. All patients were discharged with sec-
University Hospital, Norway. The hospital serves a well- ondary prevention in accordance with national guidelines.5
defined catchment area of 500,000 people, which is the The study was approved by the Regional Committee
highest population figure served by 1 stroke unit in for Ethics in Medical Research (approval number [2017/
Norway. All patients with suspected cerebrovascular disease 93]) and by the Data Protection Authorities at Akershus
are admitted to the hospital’s stroke unit. The hospital University Hospital.
has implemented a process of care for patients with TIA
that include immediate hospitalization, examination, and Statistical Analyses
treatment by a stroke physician, standardized investiga-
The statistical analyses were performed using SPSS Sta-
tions with computed tomography (CT) or diffusion-
tistics 22 (SPSS Inc., Chicago, IL). Continuous variables
weighted magnetic resonance imaging (MRI), vascular
are presented as mean and standard deviation. Categor-
examination with ultrasound or angiography, electrocar-
ical data are presented as frequencies and percentages.
diogram and Holter examination, when indicated. The
Comparisons between groups were performed with Mann-
medical records are electronic.
Whitney U for skewed continuous data, or independent
We retrospectively identified all acute admitted patients
sample t test for normally distributed continuous vari-
discharged with a diagnosis of TIA who were hospitalized
ables. Normality of continuous variables was assessed by
as emergency patients from January 1, 2013 to December
inspecting the histograms. For the categorical variables
31, 2013. Patients were identified through the diagnosis
we used chi-square test or Fisher’s exact test (as appro-
code in the medical records using the International Clas-
priate). All significance tests were 2-tailed, and a P value
sification of Diseases, Tenth Revision code G45.x. Two
of <.05 was considered significant. To determine inde-
experienced neurologists and stroke experts reviewed the
pendent predictors of recurrent stroke, univariate and
medical records. When there was uncertainty regarding
multivariate logistic regression analyses were per-
the TIA diagnosis, the medical record was re-evaluated
formed. Predictive variables explored were age, gender,
before the patient was included into the study. Read-
hypertension, atrial fibrillation, diabetes, and earlier isch-
mission data were registered until December 31, 2015.
emic events.
Patients with recurrent stroke were identified, and the
time from the qualifying TIA to the stroke was recorded
Results
in number of days. Recurrent stroke was defined as new
onset of symptoms ≥24 hours after the incident event not In total, 270 patients with the TIA diagnosis were iden-
caused by other systemic or neurologic causes other than tified. After re-evaluation of the medical records 9 were
stroke.2 Data to calculate the ABCD2 score (age, blood classified as stroke mimics, leaving 261 patients for the
pressure, clinical features, diabetes, and duration of final analyses. Mean age was 70.7 years (range 21-102),
 ARTICLE IN PRESS
STROKE RISK AFTER TRANSIENT ISCHEMIC ATTACK 3
Table 1. Clinical characteristics of the studied population

Total Recurrent stroke No recurrent stroke P value

Clinical features
n 261 11 250
Age (y) 70.7 (13.0) 67.6 (9.05) 70.8 (13.18) .435*
Male sex 132 (50.6%) 6 (54.5%) 126 (50.4%) .999†
Medical history
Hypertension 146 (55.9%) 8 (72.7%) 138 (55.2%) .356†
Atrial fibrillation 54 (20.7%) 2 (18.2%) 52 (20.8%) .999†
Diabetes mellitus 42 (16.1%) 3 (27.3%) 39 (15.6%) .392†
Cerebrovascular disease 83 (31.8%) 9 (81.8%) 74 (29.6%) .001†
Symptom duration
<10 min 38 (14.6%) 3 (27.3%) 35 (14.0%) .205†
10-60 min 98 (37.5%) 3 (27.3%) 95 (38.0%) .544†
>60 min 125 (47.9%) 5 (45.5%) 120 (48.0%) .999†
Clinical symptoms
Unilateral paresis 127 (48.7%) 8 (72.7%) 119 (47.6%) .129†
Language or speech disturbance 83 (31.8%) 2 (18.2%) 81 (32.4%) .511†
BP > 140/90 (mm Hg) 216 (82.8%) 10 (90.9%) 206 (82.4%) .695†
ABCD2 4.4 (1.3) 4.8 (1.25) 4.4 (1.28) .237‡

Continuous variables are presented as mean (SD). Categorical variables are presented as counts (percentage).
*Independent samples t test.
†Chi square test.
‡Mann-Whitney U.

and 49.4% were female. Patient characteristics are pre- 30% in the non-recurrence group (P = .001). In univariate
sented in Table 1. and multivariate analyses, a history of cerebrovascular
The most frequent TIA symptoms were unilateral facial disease was also found to be the only independent pre-
or arm or leg paresis (49%) and speech disturbance (32%). dictor of stroke recurrence (Table 2).
The third most prevalent symptom was visual distur-
bance, including unilateral visual loss; 47.9% reported
Discussion
symptoms lasting longer than 60 minutes (Table 1).
A total of 11 patients (4.2%) had a recurrent stroke during In the present study, we assessed the risk of stroke re-
the follow-up period. There were 2 recurrences within the currence after TIA among patients admitted as emergency
first 48 hours (.8%), and 2 between day 2 and 30 (.8%), to an acute stroke unit. None of the patients were strati-
which gives a 30-days stroke recurrence rate of 1.5%. Nine fied according to risk before admittance, and they all
(3.4%) had a stroke recurrence within a year. The median underwent the same fast-track evaluation and initiation
time from TIA until recurrent stroke was 90 days. Ac- of treatment and prevention.
cording to the Trial of Org 10172 in Acute Stroke Treatment Summarized, our results demonstrate a very low short-
classification, the etiology was large-vessel disease in 13.4%, and long-term risk of stroke recurrence. The risk is much
cardioembolic in 18.4%, small-vessel disease in 32.2%, and lower than the rates of cerebrovascular events reported in
other or undetermined in 36%. studies conducted when only high-risk patients were re-
Of the 11 patients with recurrence, 2 had in-hospital ferred to urgent assessment, but it is in line with some
recurrence. The 9 patients with recurrence after dis- contemporary studies.16 However, a short-term risk of only
charge all complied with the recommended antithrombotic .8% is among the lowest rates reported. In a Danish study
and antilipidemic treatment at the time of recurrence. Four conducted in a stroke unit in Aarhus, a cumulative stroke
of the 9 were daily smokers and none of them had stopped rate of 1.6%, 2.0%, and 4.4% after 7, 90, and 365 days, re-
smoking at the time of the recurring stroke. spectively, was found,11 and in a large multicenter trial
The mean ABCD2 score was 4.8 in the stroke recur- conducted from 2009 until 2011 the stroke rates at day 2,
rence group and 4.4 in the none-stroke recurrence group 30, and 365 were 1.5%, 2.8%, and 5.1%, respectively.12 The
(P = .23). The 2 patients with recurrent stroke within 48 results of these contemporary studies support the claim that
hours had ABCD2 scores of 2 and 5, respectively. The acute admission of all patients with TIA is followed by a
only variable that proved to be significantly different very low stroke recurrence rate. This outcome may be ex-
between the 2 groups was history of cerebrovascular disease, plained by an early establishment of the TIA etiology, and
with a prevalence of 82% in the recurrence group and the immediate initiation of proper secondary prevention.13
 ARTICLE IN PRESS
4 T. VIGEN ET AL.
Table 2. The association between stroke recurrence and cardiovascular risk factors

Univariate analyses Multivariate analyses

Variables OR CI P value OR* CI P value

Age 1.03 .940-1.027 .434 .96 .904-1.012 .119

Gender 1.18 .351-3.970 .788 .77 .206-2.871 .697
Hypertension 2.16 .561-8.349 .262 1.47 .320-6.721 .621
Diabetes 2.03 .515-7.986 .312 1.40 .301-6.540 .666
Atrial fibrillation .85 .177-4.036 .834 1.11 .198-6.227 .917
History of cerebrovascular disease 10.70 2.258-50.732 .003 12.44 2.365-65.448 .003

*Adjusted for age, gender, hypertension, diabetes, atrial fibrillation, and history of cerebrovascular disease.

The low number of recurrences may also reflect a change reliably discriminate between patients at low and pa-
in the panorama of stroke and TIA, including etiology, tients at high risk of recurrent stroke.9
lifestyle factors, and medical treatment before hospital- During the last decades, the World Health Organiz-
ization. In a longitudinal study from Poland, it was found ation’s definition of TIA has been debated. In 2009, the
that between 1995 and 2013 the stroke patients became American Heart Association and the American Stroke As-
older, had more comorbidity, and were therefore more sociation implemented a new tissue-based definition to
likely to use antihypertensives, antiplatelets, anticoagu- differentiate between TIA and stroke. TIA was then defined
lants, and statins pre-stroke.17 Furthermore, there are as a transient episode of neurologic dysfunction caused
indications of a decrease in stroke and TIA from athero- by focal brain, spinal cord, or retinal ischemia, without
sclerosis, but not from embolism.18 Similar trends were acute infarction.27
found in a Canadian study, where a rise and relative in- It has also been suggested to revise the time-based def-
crease in strokes caused by cardioembolism were inition for TIA symptoms from 24 hours to 1 hour.28 Based
highlighted.19 Anticoagulation to prevent TIAs and strokes on the results of our study, this would mean that 47.9%
of cardioembolic origin is much more effective than of the patients would not be diagnosed with TIA, because
antiplatelets against cerebrovascular disease of non- of the duration of symptoms. Another 2.3% of the pa-
embolic origin. Hence, a higher proportion of cardioembolic tients who underwent MRI (31%) would be redefined as
TIAs may result in a more effective secondary prevention. a stroke because of the tissue-based TIA diagnosis. There
Advances in medical secondary prevention, such as are many caveats associated with the new tissue-based
double antiplatelet therapy and increased use of statins, TIA diagnosis, however, and according to a recent meta-
may have contributed to the reduction in stroke recur- analysis it was not considered cost-effective to use MRI
rence rates. 20,21 In the future, new and safer oral for secondary stroke prevention.29 Thus, it remains un-
anticoagulants, like the factor Xa inhibitors and the direct certain where the line of differentiation between stroke
thrombin inhibitors, may increase the use of anticoagu- and TIA will be drawn in the future, and how this will
lation. This may affect the use of oral anticoagulation in influence TIA incidence and stroke recurrence rates.
patient groups that hitherto have been excluded because
of safety concerns.22-24 In addition, current guidelines em-
Strengths and Limitations
phasize carotid thrombendarterectomy or stenting at an
early stage in patients with symptomatic carotid stenosis.25 The strength of our study is that it includes unselected
It is likely that each of these medical advances con- patients with TIA admitted to 1 hospital with access to
tributes to a reduction in stroke recurrence risk, although a large stroke unit. A TIA diagnosis is based on the in-
none of them are effective unless the patients are iden- terpretation of symptoms referred by the patient. It is
tified and treated. Hence, the benefit of immediate accordingly crucial in TIA research to ascertain an accu-
recognition, urgent examination, and treatment to avoid rate diagnosis. In this study, the patients were admitted
recurrent stroke must be emphasized. to a large academic hospital and evaluated by experi-
The ABCD2 score was developed by Johnston et al. enced stroke neurologists.
in 20076 based on their ABCD score from 2005.26 It was The main limitations of our study are the retrospec-
derived for use in primary care to identify patients at tive design and the relatively small sample size. We had
high risk of recurrent stroke and in need of urgent eval- a low number of MRIs to evaluate signs of acute infarc-
uation. In the present study, the ABCD2 score failed to tion, and the cardiovascular risk profile could have been
predict risk of recurrence. Our finding is in line with a more detailed. Moreover, the ABCD2 score was calcu-
recent meta-analysis, concluding that the score does not lated from records and not on presentation and based
 ARTICLE IN PRESS
STROKE RISK AFTER TRANSIENT ISCHEMIC ATTACK 5
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care. Classification of subtype of acute ischemic stroke.
In conclusion, urgent admission of patients with TIA Definitions for use in a multicenter clinical trial. Toast.
Trial of org 10172 in Acute Stroke Treatment. Stroke
in stroke units is associated with a very low risk of stroke 1993;24:35-41.
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attack: frequency and risk factors. Stroke 2015;46:1031-
1037.
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