Who is the man in the picture?

a) Osama Bin Laden

b) Charles Darwin
c) Loui Pasteur
d) Charles Dickens
e) Barack Hussein Obama
A Journal of the life of
Charles Dickens 1869-1870
In 1869 wrote a letter to W.H.
Willis MD, mentioning
difficulties speaking and
moving foot

Jan. 1870 new years day at
Gads Hill suffering another
attack of the foot trouble

Jan 23 complains: something
the matter with my right
thumband cant write plainly

June 8
th
: writing Edwin Drood
and suffers a stroke at Dinner.

A.Tamayo U of M
TRANSIENT ISCHEMIC ATTACK

A.Tamayo U of M
Transient Ischemic
Attack
From Definition to Treatment
Arturo Tamayo MD, FAHA
Assistant Professor of Neurology U of M
Director of the Stroke Prevention Clinics
BRHA and WHSC
Disclosures
Research board member and lecturer to
the Heart and Stroke Foundation of
Canada.
Member of the Steering Committee of the
Canadian Stroke Strategy and Consortium
Speakers Honoraria: Pfizer, Allergan, and
Schering-Plough
NO STOCKS in pharmaceutical industry
A.Tamayo U of M
TIA The Problem
TIA and its
implications has
evolved over the last
decade implicating:
a) Definition
b) Risk stratification
c) Acute decision
making-management
d) Prognosis

A.Tamayo U of M
What is the definition of TIA?
a) Transient deficit lasting less than 24 hrs.
b) Deficit which improves (but not resolves)
within 24 hours.
c) Transient deficit lasting less than 30 min.
d) Transient deficit lasting up to an hour.
e) All of the above

TIA: Definition
TIA was defined as an episode of focal,
transient neurological deficit of vascular
etiology that resolve in less than 24 hrs.
NINDS classification of CVD. Stroke 1990; 21:637.

Definition NOT ANYMORE accepted


Incorrect and inaccurate
A.Tamayo U of M
TIA: Definition
A.Tamayo U of M
TIA
The Incidence and Prevalence

A.Tamayo U of M


NSA sponsored telephone survey
A total of 175,000 phone calls
Only 8.6% was able to identify symptoms
10,112 participants:

2.3% (95% CI, 2.0-2.6%) had Dx of TIA
given by a physician
only 64% saw a physician within 24 hrs.
2.3% were diagnosed as Stroke.
19 of them had a previous TIA.
3.2% had a TIA but were not seen by a
doctor

Projecting results to US population:
4.9 million of people have been
diagnosed with TIA

Univariate analysis:

History of TIA was more common in the
elderly
Those with lower income
Fewer years of education
Neurology.2003;60:1429-34
A.Tamayo U of M









That is: In 2002: 204,000 TIAs in USA
Stroke. 2005;36:720-723.
A.Tamayo U of M
NEW DEFINITION
TRANSIENT ISCHEMIC ATTACK

TIA is a brief episode of neurological
dysfunction caused by focal brain or retinal
ischemia, with complete resolution of
symptoms in less than an hour and
without evidence of infarction.
NEJM. 2002; 347:1013-1016.
A.Tamayo U of M
TIA old vs. new definition
Time Based
Deficit < 24 hours.

Suggests Benign

Delays Intervention

Inaccurately predicts
ischemia.

Diverges from CAD
tPA- Could be a TIA
Tissue Based
<1 hr event without
evidence of infarction.
Indicates potential
ischemic danger.
Encourage IMAGING and
intervention
Good ischemic predictor


Consistent with CAD
tPA- Almost all are stroke


A.Tamayo U of M










Stroke 1999;30:1174
A.Tamayo U of M
TIA The Problem
TIA and its
implications has
evolved over the last
decade implicating:
a) Definition
b) Risk stratification
c) Acute decision
making-management
d) Prognosis

A.Tamayo U of M
Which one of the following is true?
a) TIA patients are on higher risk of stroke
within 3 months
b) Most of patient with TIA present with a
stroke within a week of first event
c) The risk differs if they have hemispheric
or retinal symptoms
d) They are on high risk of cardiovascular
problems
e) All of the above

Stroke Risk after a TIA
Study N Stroke Risk

Whisnant, et al 198 10.0%/90d
Johnston, et al 1707 10.5%/90d
Johnston, et al (Kaiser C) 976 8.4%/90d
Eliazsew (NASCET) 603 20.1%/90d
Panagos, et al 790 13.3%/90d
FASTER (CANADA) 150 25.0%/90d
Lovett, (Oxfordshire) 209 12.0%/30d
Biller, et al 55 9.1% / 6 d
Putman, et al 74 6.8%/6 d

Average 13.3% Stroke Risk in 90 Days after TIA
A.Tamayo U of M
The Northern California TIA Study
JAMA.2000:13;284(22):2901-6

Northern California Keiser district
16 hospitals
2.9 million covered
Representative of the San Francisco Bay

Patients given diagnosis of TIA @ ER.
March 1997- Feb 1998.
Follow up for record review for 3 months

Settings
Cohort Study
A.Tamayo U of M
The Cohort
JAMA 2000:13;284:2901-6
N= 1707 patients.
Mean 72 yo.
53% females.
Median spell 70 min.
3 months risk of stroke 10.5%
1 week risk of stroke ... 6.0%
Recurrent TIA 13.2%
Cardiovascular hospitaliz 2.7%
Death.. 2.6%
Any of these events. 26.2%
A.Tamayo U of M
Higher risk of stroke within 7 days
JAMA 2000;284:2901-2906
Kaplan-Meier Survival-Free from Stroke
Patients Presenting with TIA in Emergency Room (N=1707)
10.5%
High risk of stroke during 1st few days after TIA
A.Tamayo U of M
What did we learn from NASCET and TIA?
Eliasziw M. et al. CMAJ 2004;30:170(7)1105-9
A.Tamayo U of M
TIA STRATIFICATION
The California TIA RISK SCALE
Age > 60

DM

Duration of episode > 10
min

Unilateral weakness

Speech impairment

A.Tamayo U of M
The California Score
A.Tamayo U of M
Risk Stratification with ABCD2






*2-day stroke risk: 1%(0-3 points), 4% (4-5 points), 8% (6-7
points)
*90 day stroke risk up to 25%
Lancet 2007; 369:283-92
Age 1 point if > 60 years
Blood pressure 1 point if sBP >140 or dBP >90
Clinical
features
2 points for unilateral weakness;
1 point speech deficit without
weakness
Duration 2 points if >60 min; 1 point if
>10-59 min
Diabetes 1 point
A.Tamayo U of M
Defining high risk.
ABCD2 + MRI (DWI / intracranial vessel occlusions)









Coutts et al. Int J. Stroke 2008; Ann Neurol 2005 A. Tamayo U of M
TIA The Problem
TIA and its
implications has
evolved over the last
decade implicating:
a) Definition
b) Risk stratification
c) Acute decision
making-management
d) Prognosis

A.Tamayo U of M
TIA- is an emergency!
WHEN SHOULD WE TREAT?







Half of all strokes occur in the first 2 days after TIA
Gladstone et al. CMAJ 2004 A.Tamayo U of M
When to Treat?
23% of patients with ischemic stroke have had a
TIA before their stroke

a) 17% occur the day of the stroke
b) 9% occurred the previous day
c) 43% had a TIA during the 7 days prior

Pooled analysis from population and RCTs (OXCASC, OCSP, UK-
TIA and ECST)
Rothwell & Warlow, Neurology 2005;64:817

A.Tamayo U of M
ER ASSESSMENT
Points to remember:
ABCD2 score has a sensibility of 80%,
that is, there are 20% of patients that can
be missed.
This scale was not include patients on
Atrial Fibrillation who are on extreme risk!
A.Tamayo U of M
3-Month Stroke Risk
According to Etiological subtype










Lovett et al. Neurology 2004: Meta analysis, n=1709
A.Tamayo U of M
Extracranial Vessel Disease

A.Tamayo U of M
TCD and Carotid Microemboli

A.Tamayo U of M
ANTIPLATELETS

A.Tamayo U of M
PLAVIX LOADING DOSE
225-300 mg
Rationale
NOT PROVEN EXPERIENCE IN STROKE
PATIENTS. ONE TRIAL ON ITS WAY. However:
a) Acute coronary syndromes: Dosages between
200-300mg inhibit in 15 minutes sCD 40 ligand
(sCD40L) and CRP (?).
b) Better outcome.
Am Heart J. 2006; 151(2):521 e1-e4.
Cure Study. Am Heart J. 2005;150(6) 1177-85.
Circulation 2005.112(19):2946-2950.
A.Tamayo U of M
A.Tamayo U of M
0-2 4-12 2-4 >12
Time from event to randomization (weeks)
5-year ARR
in stroke
(%)
Timing of Surgical Intervention
The NASCET and ECST Studies
Lancet 2004;363:915-24.
30.2
14.8
17.6
3.3
11.4
4
8.9
-2.9
40
30
20
10
0
-10
70 to 99% stenosis
50 to 69% stenosis
NNT=3
NNT=7
Numbers above bars indicate actual absolute risk reduction. Vertical bars are 95% CIs
A.Tamayo U of M
CAROTID STENTING

A.Tamayo U of M
CREST TRIAL= CAE








Brott TG. N.Engl J Med 2010;363:498
A.Tamayo U of M
Atrial Fibrillation

One of the strongest known
independent risk factor for
ischemic stroke.

Etiology usually divided into
valvular and non-valvular
disease and into permanent
vs. paroxystic.

Poorly organized contractions
result in sluggish atrial blood
flow (> left atrial appendage)
favoring thrombus formation.

Thrombi composed from
deposits of fibrin and platelets.

Marder VJ, Chute DJ, Starkman S, et al.
Analysis of thrombi retrieved from cerebral
arteries of patients with acute ischemic
stroke. Stroke 2006:37;2086-2093.

A.Tamayo U of M
2004 ACCP Guidelines for risk stratification and
antithrombotic guidelines for NVAF
Risk
Category
Annual risk of
Stroke
Antithrombotic
therapy
High
>75, prior ischemia, HBP,
DM, CHF, +/- LVD
6-12%
( CHADS2: 3-6 )
Warfarin
(INR 2.0-3.0)
Moderate
Age 65-75, none of the
above.
~ 3%
( CHADS2: 1-2 )
Warfarin or
Aspirin
Low
<65 with none of the above
~ 1%
( CHADS2: 0 )
Aspirin
Chest.2004;126:429S-456S.
A.Tamayo U of M
Warfarin vs No treatment
Primary Prevention
Five major primary
prevention trials
consistently showed:
a) RRR 68% per year.
b) NNT 32
c) Reduced combined
outcome by 48%
(stroke, systemic
embolism or death)
Ezekowitz MD. N Engl J
Med.1992;327:1406-1412
Secondary Prevention
Secondary stroke
prevention RRR by
66% (12% risk in
untreated vs 4%
treated).
NNT 13
No hemorrhagic
differences among
groups
EAFT Study. Lancet.
1993;342:1255-1262

A.Tamayo U of M
Hylek EM. N Engl J Med. 2003;349:1019-1026.
A.Tamayo U of M
Stroke or systemic embolism (SSE)
0.50 0.75 1.00 1.25 1.50
Dabigatran 110 mg
vs. warfarin
Dabigatran 150 mg
vs. warfarin
Noninferiority
p-value
<0.001
<0.001
Superiority
p-value
0.34
<0.001
M
a
r
g
i
n

=

1
.
4
6

HR (95% CI)
Connolly SJ., et al. NEJM published online on Aug 30th 2009.
DOI 10.1056/NEJMoa0905561
Dabigatran etexilate is in clinical development and not licensed for
clinical use in stroke prevention for patients with atrial fibrillation
A.Tamayo U of M
Vascular Risks
HYPERTENSION

The most important modifiable risk
factor (2-5x)
Ischemic bleeding,
Silent strokes

Contributes to
Large vessel disease
Small vessel (lacunar)
LV dysfunction

Treatment reduces risk 40%

CHEP:
<140/90 (in DM <130/80)


Stroke. 2006;37:577-617
A.Tamayo U of M
Vascular Risks
Diabetes: Increases x 2 the risk of Stroke.
Highly correlated with HTN, and metabolic
syndrome.
Treatment reduces microvascular
complications>macrovascular.
Cholesterol: Doubles the risk of stroke.
Risk for CAD. SPARCL (NNT = 50)
A.Tamayo U of M
TIA The Problem
TIA and its
implications has
evolved over the last
decade implicating:
a) Definition
b) Risk stratification
c) Acute decision
making-management
d) Prognosis

A.Tamayo U of M
EXPRESS Study
Rothwell et al. Lancet 2007
Phase 1 vs. 2
90 days stroke risk
from 10% to 2%
Medications started
right away
Carotid
endarterectomy
expedited









A. Tamayo U of M
RECOMMENDATIONS
IN THE ER: The Never and Ifs rules
NEVER FORGET THE TIA CANADIAN GUIDELINES
Play SAFE! (never play un-safe)
Never discharge If not sure; consult Neurologist on Call!
Never discharge a patient unless mayor risk factors and
images have been done.
(managing hypertension, hyperglycemia, electrolytes
imbalance) and CT of brain and carotid images are
available. If severe stenosis consult neurology.
Never discharge a patient with crescendo TIAs
Never discharge a patient with mild deficits (that is a
stroke)
Never discharge a patient on Atrial Fib.
A.Tamayo U of M
My Recommendations in ER (2)
If ABCD2 score is 0-3 points and patient is
stable; REFERRAL TO STROKE CLINIC
(all patients should be seen within 3 days)
If ABCD2 score is 4-5; patient should be seen in
ER by Neurology.
If large or small vessel disease is suspected:
load patient with Clopidogrel (75mg x 3).
If Patient is on Atrial Fibrillation: Patient should
be admitted on IV heparin and a
transesophageal echo should be requested to
rule out: Atrial appendage thrombus

A.Tamayo U of M
Current Research
A) TIA Hotline
B) Triage TIA scale
Project designer:
Susan Alcock RN
(WRHA)

Brandon-Winnipeg
Stroke Clinic Team
MANITOBA STROKE
PREVENTION CLINICS
Brandon Regional Health Centre
Tel: 578 - 2165 Fax: 578 - 4956
Steinbach Regional Health Centre
Tel: 320 - 4177 Fax:320 - 4171
Winnipeg Health Sciences Centre
Tel: 787-1121 Fax: 787- 3803
Winnipeg St. Boniface Health Centre
Tel: 235 330 Fax: 233 - 3285

A.Tamayo U of M
Any Questions?








Thank you!