Transcript Transient Ischemic Attack From Definition to Treatment

Who is the man in the picture?
a)
b)
c)
d)
e)
Osama Bin Laden
Charles Darwin
Loui Pasteur
Charles Dickens
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 year’s day at
Gad’s Hill suffering another
attack of …”the foot trouble”
• Jan 23 complains: “something
the matter with my right
thumb…and can’t write plainly”
• June 8th : 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
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•
•
•
•
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
Whisnant, et al
Johnston, et al
Johnston, et al (Kaiser C)
Eliazsew (NASCET)
Panagos, et al
FASTER (CANADA)
Lovett, (Oxfordshire)
Biller, et al
Putman, et al
198
1707
976
603
790
150
209
55
74
Stroke Risk
10.0%/90d
10.5%/90d
8.4%/90d
20.1%/90d
13.3%/90d
25.0%/90d
12.0%/30d
9.1% / 6 d
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
•
Settings
Northern California Keiser district
16 hospitals
2.9 million covered
Representative of the San Francisco Bay
•
Cohort Study
Patients given diagnosis of TIA @ ER.
March 1997- Feb 1998.
Follow up for record review for 3 months
•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……
1 week risk of stroke ……...
• Recurrent TIA………………
• Cardiovascular hospitaliz…
• Death………………………..
• Any of these events……….
10.5%
6.0%
13.2%
2.7%
2.6%
26.2%
A.Tamayo U of M
Higher risk of stroke within 7 days
Kaplan-Meier Surv iv al-Free f rom Stroke
Patients Presenting with TIA in Emergency Room (N=1707)
10.5%
High risk of stroke during 1st few days after TIA
JAMA 2000;284:2901-2906
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What did we learn from NASCET and TIA?
Eliasziw M. et al. CMAJ 2004;30:170(7)1105-9
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TIA STRATIFICATION
The California TIA RISK SCALE
• Age > 60
• DM
• Duration of episode > 10
min
• Unilateral weakness
• Speech impairment
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The California Score
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Risk Stratification with ABCD2
Age
Blood pressure
Clinical
features
Duration
Diabetes
1 point if > 60 years
1 point if sBP >140 or dBP >90
2 points for unilateral weakness;
1 point speech deficit without
weakness
2 points if >60 min; 1 point if
>10-59 min
1 point
*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
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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
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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, UKTIA 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!
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3-Month Stroke Risk
According to Etiological subtype
• Lovett et al. Neurology 2004: Meta analysis, n=1709
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Extracranial Vessel Disease
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TCD and Carotid Microemboli
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ANTIPLATELETS
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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
Timing of Surgical Intervention
The NASCET and ECST Studies
40 NNT=3
30
5-year ARR
in stroke
(%)
70 to 99% stenosis
30.2
50 to 69% stenosis
NNT=7
20
17.6
14.8
11.4
8.9
10
3.3
4
0
-2.9
-10
0-2
2-4
4-12
>12
Time from event to randomization (weeks)
Numbers above bars indicate actual absolute risk reduction. Vertical bars are 95% CIs
• Lancet 2004;363:915-24.
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CAROTID STENTING
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CREST TRIAL= CAE
•
Brott TG. N.Engl J Med 2010;363:498
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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
6-12%
>75, prior ischemia, HBP,
DM, CHF, +/- LVD
( CHADS2: 3-6 )
Warfarin
(INR 2.0-3.0)
Moderate
~ 3%
Age 65-75, none of the
above.
( CHADS2: 1-2 )
Low
~ 1%
<65 with none of the above
( CHADS2: 0 )
Warfarin or
Aspirin
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
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M
Hylek EM. N Engl J Med. 2003;349:1019-1026.
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Stroke or systemic embolism (SSE)
Noninferiority
p-value
Dabigatran 110 mg
vs. warfarin
Margin = 1.46
Dabigatran 150 mg
vs. warfarin
0.50
0.75
1.00
1.25
Superiority
p-value
<0.001
0.34
<0.001
<0.001
1.50
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 U
notoflicensed
for
A.Tamayo
M
clinical use in stroke prevention for patients with atrial fibrillation
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!