Current treatment of transient ischemic attack

CURRENT MANAGEMENT OF
TRANSIENT ISCHEMIC ATTACK
Sen. Col.Assoc. Prof. Samart Nidhinandana
Director of department of Psychiatry and Neurology
Head of PMK Stroke Center
Phramongkutklao Hospital and College of Medicine
Friday, August 22, 2014

ชายไทยคู่อายุ 78 ปี
วันที่6 กุมภาพันธ์ 06.20 น.มีอาการแขนขาด้านขวาอ่อนแรง มาถึง
รพ.เวลา 10.42 น.
สัญญาณชีพ ความดันเลือด 140/80 มม.ปรอท อัตราชีพจร 88 ครั้ง
ต่อนาที อัตราการหายใจ 20 ครั้งต่อนาที
ตรวจร่างกาย ปกติ ไม่พบอาการอ่อนแรง
ตรวจระดับน้ำตาลในเลือดจากปลายนิ้วได้ 99 มก./ดล. ตรวจ
ปัสสาวะปกติ แพทย์ให้คำวินิจฉัยว่า Transient Ischemic Attack
และให้คำแนะนำ นัดมาตรวจเลือดหาระดับน้ำตาล ไขมัน วันที่11
กุมภาพันธ์

คำถาม
ท่านคิดว่าแพทย์ให้การวินิจฉัย และการรักษาถูกต้องหรือไม่ ?

คำจำกัดความ
TRANSIENT ISCHEMIC ATTACK
Transient episode of neurological dysfunction caused by
focal brain, spinal cord, or retinal ischemia, without acute
infarction.
Easton JD., Saver JL.,Albers GW et al.Stroke 2009;40:2276-2293.

ABCD2
score case
Age>60 1 1
BP>140 1 1
Clinical
Focal deficit 2 2
Dysarthria 1 0
Duration
>60 min 2 2
10-59 min 1 0
DM 1 0

STROKE RISK USING ABCD2 SCORE
Two-day risk of stroke in combined validation cohorts
ABCD2 SCORE STROKE RISK
0 - 1 0%
2 - 3 1.3%
4 - 5 4.1%
6 - 7 8.1%
No randomized trial has evaluated the utility of the
ABCD2 score in assisting with triage decisions

Multicenter study of early stroke risk based on ABCD2 score and tissue-vs.
time-defined TIA (n = 4574)
Giles MF et al., Neurology 2011;77:1222-1228

HOSPITALIZATION
Hospitalization rates after TIA vary widely among
practitioners, hospitals, and regions
Close observation during hospitalization has the potential to
allow more rapid and frequent administration of tPA should
a stroke occur.
Other benefits: cardiac monitoring , rapid diagnostic
evaluation, greater rates of adherence to secondary
prevention interventions.
No randomized trial has evaluated the benefit of
hospitalization

CLASS I RECOMMENDATION
1. Patients with TIA should preferably undergo neuroimaging
evaluation within 24 hours of symptom onset. MRI, including
DWI, is the preferred brain diagnostic imaging modality. If MRI
is not available, head CT should be performed (Class I, Level B).
2. Noninvasive imaging of the cervicocephalic vessels should be
performed routinely as part of the evaluation of patients with
suspected TIAs (Class I, Level A )

CLASS I RECOMMENDATION
3. Noninvasive testing of the intracranial vasculature reliably
excludes the presence of intracranial stenosis (Class I, Level A)
and is reasonable to obtain when knowledge of intracranial
steno-occlusive disease will alter management. Reliable
diagnosis of the presence and degree of intracranial stenosis
requires the performance of catheter angiography to confirm
abnormalities detected with noninvasive testing.
4. Patients with suspected TIA should be evaluated as soon as
possible after an event (Class I, Level B).

CLASS II RECOMMENDATION
1. Initial assessment of the extracranial vasculature may
involve any of the following: carotid ultrasound/TCD, MRA or
CTA, depending on local availability and expertise, and
characteristics of the patient (Class IIa, Level B).
2. If only noninvasive testing is performed prior to
endarterectomy, it is reasonable to pursue two concordant
noninvasive findings; otherwise catheter angiography should
be considered (Class IIa, Level B).

3. The role of plaque characteristics and detection of
microembolic signals is not yet defined (Class IIb, Level B).
4. Electrocardiography should occur as soon as possible after
TIA (Class I, Level B). Prolonged cardiac monitoring (inpatient
telemetry or Holter monitor) is useful in patients with an
unclear etiology after initial brain imaging and
electrocardiography (Class IIa, Level B).

5. Echocardiography (at least TTE) is reasonable in the
evaluation of patients with suspected TIAs, especially when the
patient has no cause is identified by other elements of the work-up
(Class IIa, Level of Evidence B). TEE is useful in identifying
patent foramen ovale, aortic arch atherosclerosis, and valvular
disease and is reasonable when identification of these
conditions will alter management (Class IIa, Level of Evidence B).
6. Routine blood tests (complete blood count, chemistry panel,
prothrombin time and partial thromboplastin time, and fasting
lipid panel) are reasonable in the evaluation of patients with
suspected TIAs (Class IIa, Level of Evidence B).

It is reasonable to hospitalize patients with TIA if they present
within 72 hours of the event and any of the following criteria
are present:
ABCD2 score of ≥3, (Class IIa, Level C).
ABCD2 score of 0-2 and uncertainty that diagnostic work-up
can be completed in 2 days as an outpatient (Class IIa, Level C).
ABCD2 score of 0-2 and there is other evidence that indicates
patient’s event was caused by focal ischemia (Class IIa, Level C).

Transient Ischaemic Attack
(TIA)
Cranial CT
Carotid Doppler
Ultrasound
Normal 30-70% stenosis +/- “non-surgical” plaque
Look for other sources of emboli
Angioplasty ± stent Endarterectomy
-Echocardiogram
-Holter monitor
MRA
Tests congruent
Medical Treatment
> 70% stenosis on appropriate side
MRA or CTA
Tests incongruent
Further non-invasive
imaging
(do alternate test)
MRA, CTA or DSA
> 70% stenosis < 70% stenosis
Tests congruent

ประวัติต่อ..
หลังกลับจากโรงพยาบาลผู้ป่วยมีอาการแขนขาด้านขวาอ่อนแรง จึง
ไปโรงพยาบาลอีกแห่ง 1800 น.วันเดียวกัน
ความดันเลือด 150/77 มม.ปรอท อัตราชีพจร 57 ครั้งต่อนาที อัตรา
การหายใจ 20 ครั้งต่อนาที อุณหภูมิกาย 37 องศาเซลเซียส ตรวจ
พบแขนขาด้านขวาอ่อนแรง
ให้การวินิจฉัยว่า หลอดเลือดสมองอุดตันเฉียบพลัน ได้ส่งตรวจ
คอมพิวเตอร์สมอง เมื่อวันที่6 กุมภาพันธ์ พบว่ามีเนื้อสมองด้าน
ซ้ายขาดเลือด จึงรับรักษาในโรงพยาบาล

ท่านจะให้การรักษาอย่างไร
Medical Treatment :
- Antithrombotic :Antiplatelet vs. Anticoagulant
- Statin ?
- Antihypertensive drug : who,what,where,when, how
- Life style modification
Intervention : angioplasty
Surgery : carotid endarterectomy

ANTIPLATELET AGENT
RECOMMENDATION
Noncardioembolic ischemic stroke or TIA
Aspirin 50-325 mg/d monotherapy or aspirin 25 mg and ER
dipyridamole 200mg twice daily after TIA for prevention
future stroke.(Revised)
Clopidogrel 75 mg monotherapy for secondary prevention or
aspirin 25 mg and ER dipyridamole 200mg twice daily.
ASA and clopidogrel 75 mg might be considered for
initiation within 24 hours of TIA and continuation for 90
days (Class IIb, level B)(New recommendation)

INTERVENTION FOR
LARGE-ARTERY ATHEROSCLEROSIS
1. TIA within past 6 mo. and ipsilateral severe (70-99%)
carotid stenosis. CEA (perioperative morbidity and
mortality risk <6%)(Class I,levelA)
2.Ipsilateral moderate (50-69%) carotid stenosis. CEA
depend on age and comorbidities.( perioperative
morbidity and mortality risk <6%)(Class I,level B)
3.Stenosis < 50%, CEA and CAS not recommended(Class
III, level A)

INTERVENTION FOR
4.Revascularization in TIA is reasonable to perform
within 2 weeks (Class IIa,level B)
5.CAS is alternative to CEA for symptomatic patients at
average to low risk of complication when ICA lumen
reduced >70%(noninvasive imaging) or > 50%
(catheter-based image)with rate of perriprocedural
stroke or death <6%(Class IIa. level B)

INTERVENTION FOR
6.CEA is considered in older patients may improved
outcome, younger patients CAS is equal to CEA (risk for
periprocedural complication and long-term for
ipsilateral stroke)(New)(Class IIa,level B)
7.Symptomatic severe stenosis (>70%)whom increase
risk for surgery, radiation-induced stenosis or
restenosis after CEA, CAS (Revised)(Class IIa,level B) CEA or
CAS should be performed (risk for periprocedural
complication and long-term for ipsilateral stroke
(Revised)(ClassI,level B)

INTERVENTION FOR
8. Routine, long-term FU imaging of extracarotid with
carotid duplex ultrasonography is not recommended.
(New)(Class III, level B)
9. Recent (6mo.)TIA or ischemic stroke ipsilateral to
stenosis or occlusion of middle cerebral or carotid
artery,EC/IC by pass is not recommended (Class III,level A)

INTERVENTION FOR
10.Recurrent or progressive ischemic symptoms ipsilateral
to stenosis or occlusion of distal (surgical inaccessible)
carotid artery,or occlusion of midcervical carotid artery
after institutional of optimal medical therapy, EC/IC is
considered(New)(Class IIb,level C)
11. Optimal medical therapy, antiplatelet, statin and risk
factors modification is recommended for carotid artery
stenosis and TIA or stroke (Class I,level A)

EXTRACRANIAL VERTEBROBASILAR
DISEASE RECOMMENDATIONS
1. Preventive therapy with antithrombotic therapy, lipid
lowering, BP control, lifestyle optimization in symptomatic
extracranial vertebral artery stenosis (Class I,level C)
2. Endovascular stenting with extracranial vertebral stenosis
have symptom despite optimal medical treatment (Class IIb,level C)
3. Open surgical procedures, including vertebral endarterec -
tomy and vertebral artery transposition in symptomatic despite
optimal medical treatment (Class IIb, level C)

INTRACRANIAL
ATHEROSCLEROSIS
1.WASID study 569 stroke or TIA 50-99% intracranial
stenosis of MCA, intracranial ICA, intracranial VA or
basilar artery compared ASA 1300mg/d to warfarin
(INR 2-3)
2.Antiplatelet Therapy Trials
3.Intracranial

COMPARISON OF WARFARIN AND
ASPIRIN FOR SYMPTOMATIC
INTRACRANIAL ARTERIAL STENOSIS
Marc I. Chimowitz, M.B., Ch.B., Michael J. Lynn, M.S., Harriet Howlett-
Smith, R.N., Barney J. Stern, M.D., Vicki S. Hertzberg, Ph.D., Michael R.
Frankel, M.D., Steven R. Levine, M.D., Seemant Chaturvedi, M.D., Scott
E. Kasner, M.D., Curtis G. Benesch, M.D., Cathy A. Sila, M.D., Tudor G.
Jovin, M.D., and Jose G. Romano, M.D., for the Warfarin–Aspirin
Symptomatic Intracranial Disease Trial Investigators*
N Engl J Med 2005;352:1305-16.

MAJOR HEMORRHAGE AND
DEATH IN WASID
Aspirin
Events / 100
pt.yrs
Warfarin
Events/100
pt.yrs
p-value
Major Hem. 1.8 4.4 0.01
Death 2.4 5.2 0.02

PRIMARY END POINT:
STROKE AND VASCULAR DEATH
Aspirin Warfarin
No.of Patients 280 289
No. of Patients with Event 62 ( 22%) 63 (22%)
1yr / 2yr rates 15 / 21 17 / 22
Log-Rank p - value 0.83
Hazard Ratio (95% CI) 1.04 (0.73 –– 1.48)

† P values are for comparison between the aspirin group and the warfarin group and were calculated ‡ Given the number of patients recruited and the outcomes observed, if warfarin is in fact superior the probability that the study, if completed, would have resulted in a statistically significant difference Adverse Events
Figure 2. Cumulative Incidence of the Primary End Point after Randomization,
The rate of According to Treatment Assignment.
patients assigned The primary end point was ischemic stroke, brain hemorrhage, or death from
group vascular causes other than stroke.
hazard ratio, COMPARISON OF WARFARIN AND ASPIRIN
FOR SYMPTOMATIC INTRACRANIAL
ARTERIAL STENOSIS
the stenotic ischemic stroke, than stroke, were no significant treatment groups points (Table infarction or secondary more frequently aspirin group vs. 7.3 percent 0.40; 95 percent P=0.02).
P=0.83
0.4
Probability of Primary End Point
0.3
0.2
0.1
0.0
Aspirin
Warfarin
0 1 2 3 4 5
Years after Randomization
No. at Risk
Aspirin
Warfarin
18
16
59
66
120
130
192
202
280
289
Cumulative Incidence of the Primary End Point wasIschemic stroke, brain hemorrhage, or death
from vascular causes other than stroke.
Chimowitz MI., et al. N Engl J Med 2005;352:1305-16.

WASID: ISCHEMIC STROKE IN
TERRITORY OF SYMPTOMATIC
ARTERY
Aspirin Warfarin
# of Patients 280 289
# Patients with Event 42 (15%) 35 (12%)
1yr / 2yr rates 12 / 15 11 / 13
Log-Rank p – value 0.31
Hazard Ratio (95% CI) 1.26 (0.81 –– 1.97)

SAMMPRIS TRIAL
Stenting and Aggressive Medical Management for
Preventing Recurrent stroke in Intracranial
Stenosis
An Investigator-initiated and Designed
NIH / NINDS Funded Trial

SAMMPRIS TRIAL
TIA or stroke in 30 days related to 70-99% stenosis of
major intracranial compared aggressive medical
management alone to aggressive medical management
with angioplasty and stenting with Wingspan stent
system (Stryker Neurovascular, Fremont, CA, USA)

90% stenosis

AGGRESSIVE MEDICAL
MANAGEMENT
1. ASA 325 mg/d and clopidogrel 75mg/d for 90 days.
2. SBP <140 mmHg(<130mmHg in DM)
3. LDL-C <70mg/dl
4. Lifestyle modification program

RESULT OF 30-DAY RATE
Stopped april 2011, 451 were randomized.
Rate of stroke and death was higher in stenting arm (14.7%
vs. 5,8%)(P=0.002)
2.2% stroke-related deaths in stenting arm and 0.4% in
medical arm

with intracra-nial
periprocedural
expected and
management
30-day rate
(14.7%) is
previously re-ported
stent in the
rates ranging
rate in the
inexperience of the
interventionists
participat-ed
interventionists in this
the basis of
addition, the rates
decline over the
did not dif-fer
enrolling sites and
higher rate of
compared with
this study
Cumulative!Probability!of!the!Primary
End!Point
1.00
0.90
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
Medical-management
0.15
0 3 6 9 12 15
Months!since!Randomization
P=0.009
No.!at!Risk
Medical manage-ment
group
PTAS group
227
224
196
182
164
153
132
125
115
98
92
83
group
0.20 PTAS group
0.10
0.05
0.00
0 3 6 9 12 15
Rate of primary end point in 30-day PTAS was 16% and medical-management
Figure!1.!Kaplan–Meier!Curves!for!the!Cumulative!Probability!of!the!Primary!
End!Point,!According!to!Treatment!Assignment.
The primary end point was stroke or death within 30 days after enrollment
or after a revascularization procedure for the qualifying lesion during the
follow-up period or stroke in the territory of the qualifying artery beyond
group was 4.3% and 1 year were 20.9% and 12.9%,P0.028

INTRACRANIAL
ATHEROSCLEROSIS
RECOMMENDATION
STROKE OR TIA CAUSED BY 50-99% STENOSIS
OF MAJOR INTRACRANIAL ARTERY
1. TIA or stroke caused by 50-99% stenosis of major
intracranial artery, ASA 325 mg/d is recommended. (Class I,
level B)(Revised)
2.Recent stroke or TIA (within 30 days from severe stenosis
(70-99%) of major intracranial artery, add clopidogrel 75
mg/d to aspirin for 90 days.(New)(Class IIb, level B)

STROKE OR TIA CAUSED BY
50-99% STENOSIS OF MAJOR
INTRACRANIAL ARTERY
3.Data are insufficient to make a recommendation regarding the
usefulness of clopidogrel alone, aggrenox, or cilostazol alone (New)
(Class IIb,level C)
4.Maintain SBP <140 mmHg and high intensity statin therapy are
recommended (Revised)(Class I,level B)
5.Angioplasty or stenting is not recommenced (New)(Class III,level B)
6.EC/IC bypass surgery is not recommended (Class III,levelB)

INTRACRANIAL ARTERY
7.Stenting with wingspan stent system is not
recommended as initial treatment even take
antithrombotic agent(New)(Class III,level B)
8.Usefulness of angioplasty alone or placement of stent
other than stenting with wingspan stent system is
unknown (Revised)(Class IIb,level C)

INTRACRANIAL ARTERY
9.Recurrent TIA or Stroke after institution of ASA and clopidogrel
therapy, achievement of SBP < 140 mmHg, and high-intensity
statin therapy, usefulness of angioplasty alone or placement of
wingspan stent system stent other than stent is unknown (New)
(Class IIb,level C)
10.Active progressing symptoms after ASA and clopidogrel
therapy, usefulness of angioplasty alone or placement of
wingspan stent system stent other than stent is unknown (New)
(Class IIb,level C)

ANTIPLATELET AGENT
RECOMMENDATION
ASA and clopidogrel initiated days to years after TIA and
continued for 2-3 years,increases risk of hemorrhage relative
to either agent alone and is not recommended for routine
long-term secondary prevention after TIA (Class I,level A)
Patients who have an ischemic stroke or TIA while taking
ASA, no evidence that increasing dose of ASA provides
additional benefit.
Patients with history of ischemic stroke or TIA, AF and CAD,
usefulness of adding antiplatelet therapy to VKA therapy is
uncertain for purposes of reducing the risk of ischemic
cardiovascular and cerebrovascular event.

THANK YOU

Current treatment of transient ischemic attack

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