Stroke Management & Prevention

Prof Dr Tan Kay Sin, FRCP(Edin)

Senior Consultant Neurologist
University of Malaya Medical Centre
Kuala Lumpur, Malaysia
Stroke Chain of Survival and Recovery
Detection: Early recognition
Dispatch: Early EMS activation and response
Delivery: Transport and management
Door: ER triage
Data: ER evaluation and management
Decision: Specific stroke therapies
Drugs: Thrombolytic for ischemic stroke
 Critical pre-hospital
assessment
• “STROKE:CHAIN OF RECOVERY”
• ABCs; give oxygen, if needed
• Perform pre-hospital stroke assessment
• Establish time when patient was last
known to be normal
• Transport; consider transfer to hospital
with thrombolytic protocol & stroke unit
• Alert hospital
• IV cannula and glucose measurement
3
 NINDS Stroke Evaluation Targets

Door to doctor 10 mins

Door to CT completion 25 mins
Door to CT read 45 mins
Door to treatment 60 mins
Access to neuro expertise 15 mins
Access to neurosurg expertise 2 hours
Admit to monitored bed 3 hours
Cincinnati Prehospital Stroke Scale
(modified) FAST!!!
• Facial droop
• Ask patient to smile or show teeth
• Arm drift
• Patient closes eyes and holds both arms
striaght out for 10 sec
• Speech: Ask patient to repeat
“Saya suka bermain badminton
di Malaysia”
“It is hot and sunny in Malaysia”
 In Emergency Dept: Immediate General
Assessment & Stabilization within 10 minutes of
Arrival
• Review history and establish time of onset
• Assess ABC & vital signs
• Provide oxygen;IV access;Bloods: Full blood
count;PT/INR;APTT, ESR,fasting blood glucose;
fasting lipid profile, liver function test.
• ECG
• Order emergency CT brain(door to CT< 25
minutes)
• Door to CT reading(< 45 minutes)
• Activate internal medicine/stroke team
 Internal Medicine/Stroke
Assessment

• Immediate neurologic assessment by

stroke team within 25 minutes of arrival
to Emergency Dept
• Review patient history
• Establish symptom onset
• Perform neurologic assessment

7
EXCLUDE STROKE MIMICS
Is it a stroke?

Acute or sudden onset

Neurological syndrome



Referrable to an underlying
vascular pathology



Lasting from minutes (TIA)
to > 24 hrs
As much as 20 to 30% of “strokes” and “TIAs”
are mimics

Conditions that mimic stroke in the emergency department:

• Seizures • Herpes encephalitis
• Systemic infection • Transient global amnesia
• Brain tumor • Dementia
• Toxic-metabolic • Demyelinating disease
• Positional vertigo • Cervical spine fracture
• Cardiac Syncope • Myasthenia gravis
• Trauma • Parkinsonism
• Subdural hematoma • Hypertensive encephalopathy
• Conversion disorder
Other conditions to consider:
• Bell’s palsy
• Migraine
• Toxins Libman RB, et al, Arch Neurol. 1995;52:1119-22
 Beware of basilar artery
thrombosis
• Motor deficits (40-67%)
(hemiparesis, tetraparesis, facial paresis)
• Dysarthria & speech impairment (30-63%)
• Vertigo, nausea & vomiting (54-73%)
• Visual disturbance (21-33%)
• Altered consciousness (17-33%)
 What is a TIA?
▪ TIA is like “unstable angina of the
brain”
▪ TIA is a neurologic emergency
▪ Requires urgent/emergent workup
▪ MAY cause permanent brain injury
▪ More advanced imaging shows damage in up
to 50% of TIA patients (old definition)
 What is a TIA?
▪ 1975 (NIH Definition)
“ A transient ischemic attack is a sudden
focal neurologic deficit lasting for less
than 24 hours, of presumed vascular
origin, and confined to an area of the
brain or eye perfused by a specific
artery ”
 TIA: Presentation
▪ Current definition of TIA (2009) eliminated a time
frame

▪ “ A transient episode of neurological dysfunction

cause by focal brain, spinal cord, or retinal
ischemia, without acute infarction”
▪ Now is a tissue-based definition, not a
time-based definition
▪ Emphasis is now on neuroimaging
 ADMIT TO HOSPITAL VS CLINIC

1. Admit all patients with acute stroke or

recent TIA within 7 days
2. If admission is not possible for all patients,
identify high-risk TIA using ABCD2 score
3. Admit if patient has neurological
worsening, AF, carotid bruit, uncontrolled
hypertension/hypotension, fever,
dehydration, CHF, or ACS
 ABCD2 Score
Age
 ≥ 60 years =1
 < 60 years =0
Blood pressure on first assessment
 Systolic ≥ 140 and/or diastolic ≥ 90 mmHg = 1
 Systolic < 140 and diastolic < 90 mmHg =0
Clinical features
 Unilateral weakness =2
 Speech disturbance without weakness =1
 Other =0
Duration of symptoms
 ≥ 60 minutes =2
 10-59 minutes =1
 < 10 minutes =0
Diabetes
 Yes =1
 No =0

If score ≥ 4 (medium to high risk), admit patient

If score <4 (low risk), prompt evaluation in outpatient setting or TIA clinic
ABCD2 Score 2-day stroke risk
0-1 0%
2 1 - 2%
3 0 - 3%
4 2 - 5%
5 3 - 7%
6 4 - 14%
7 0 - 50%

ABCD2 Score 7-day stroke risk

<4 1.2%
Johnston SC, et al Lancet 2007; 369: 283-92.
 NEUROIMAGING

17
 Emergency Diagnostic Tests for
Stroke
Computed tomography (CT)
• Distinguishes reliably between hemorrhagic and ischaemic stroke
• Early signs of ischemia detected as early as 2 h after stroke onset
• Identifies hemorrhages almost immediately
• Detects sub-acute hemorrhage in the majority of cases
• Helps to identify other neurological diseases (e.g., neoplasms)

Magnetic resonance imaging (MRI)

• Becoming more common
• Diffusion- and perfusion-weighted MRI may help to differentiate between
infarcted tissue and tissue at risk
• More expensive than CT and not as widely available

18
 Diffusion weighted MR Imaging
*measures the microscopic movement of water protons; uses a spin echo sequence
with a pair of magnetic field pulses. Reduced movement of water molecules result in
signal loss. In stroke, cytotoxic oedema causes a hyperintense signal corresponding
to a decrease in the apparent diffusion coefficient(ADC).

19
 Investigations - Imaging
For all suspected stroke
compulsory
1. Chest x-ray (Mandatory)
2. CT brain – The emergency neuroimaging scan of choice for all
patients. Differentiates haemorrhage from infarction. Confirms
site of lesion, cause of lesion, extent of brain affected.
3. 12 Lead ECG

4. Extra and intracranial vascular

assessment - Allows identification of extracranial
vessel disease

20
 Investigations - Imaging

In Selected Patients

CT angiography (multislice CT scan) - Non invasive tool

to assess intra- and extra-cerebral circulation. Involves
intravenous contrast injection
MR venography - In suspected cerebral venous thrombosis
Digital subtraction angiogram - Gold standard
assessment of cerebral vasculature. Reserved for patients
planned for intervention

21
 Routine TCD
examination

22
 Case Study (Imaging Findings)

Transcranial Doppler(TCD)
demonstrates right distal
Left M1 middle cerebral
M1 middle cerebral artery
stenosis at 48 mm depth artery
insonation confirmed on Insonation showed normal
magnetic resonance flow
angiography(MRA)

23
 Carotid Duplex Ultrasound

24
 Brain Imaging
• In about 1% of patients with TIA, CT shows
a nonvascular lesion accounting for
neurological symptoms (e.g. tumors, SDH)
• CT and MRI may also identify other vascular
lesions such as aneurysms or
arteriovenous malformations that can be
present in patients with TIAs
• 5-10% of suspected ischemic stroke are
found to have hemorrhage on CT scan
 Clues for hemorrhagic stroke

• Headache
• Change in sensorium / Loss of
consciousness
• Vomiting
• Rapid Progression
• Severe hypertension on presentation
• Meningismus/Neck rigidity
 Computed Tomography

• Widely available, relatively inexpensive,

non-invasive, and quick
• Accurately differentiate hemorrhagic
and ischemic stroke
• Inferior to MRI in posterior fossa lesions
due to bony artifacts
CT Scan: Infarct vs ICH
CT Scan: SAH
Early Changes on CT Scan
Early Changes on CT Scan

Hyperdense
MCA sign
 Magnetic Resonance Imaging
• More expensive and less widely available
• Longer acquisition time compared to CT
- difficult in uncooperative patients
• Contraindicated in patients with metallic
implants (e.g. IOL, pacemaker)
• More sensitive in detecting small lesions
• Can detect lesions as early as 6 hours from
stroke onset (as early as 11 min for
Diffusion MRI)
MRI: Infarct vs. ICH
Early Changes on MRI
35
 ADMIT TO STROKE UNIT VS WARD
1. Admit all suspected strokes to SU, unless
co-existing conditions require ICU, etc.
2. If no SU available, admit to ward and refer
to mobile stroke team or neurologist
3. Assess and monitor neurological status
4. Start treatment and perform diagnostics
5. Multidisciplinary team care
6. Monitor for complications and treat early
7. Start education program for patient/family
 Thrombolysis

• Established treatment for stroke

• Small therapeutic window
• Intravenous recombinant tissue plasminogen activator;
rt-PA in a dose of 0.9 mg/kg (maximum of 90mg) given
over 1 hour for use within 3 hours of stroke
• 5 large trials; mainly the landmark NINDS rt-PA trial
• ECASS I and II
• Service organisation/logistics & stroke awareness remains
a major barrier to wide implementation of rt-PA.

37
 rt-PA Eligibility & Contraindications
• Age > 18 years
• Clinical diagnosis of ischemic
stroke causing a measurable
neurological deficit
• Onset of stroke symptoms well
established to be less than 4.5
hours before treatment
(ESO 2009)
38
• Strong contraindications
• Symptoms minor or rapidly
improving
• Other stroke or serious head trauma
within the past 3 months
• Major surgery within the last 14
days
• History of intracranial haemorrhage
• Sustained systolic BP > 185 mm Hg
• Sustained diastolic BP > 110 mm
Hg
• Aggressive treatment to lower blood
pressure
• Symptoms suggestive of
subarachnoid haemorrhage
• GI or urinary tract haemorrhage
within 21 days
• Heparin/thrombolytic use/48 hours
• Low platelets
 Benefits of rt-PA
• Alteplase (rtPA) is indicated for the management
of acute ischaemic stroke in adults
• NINDS trial demonstrated 30% improvement in
overall functional outcome at 3 months with the
benefits maintained at 1 year.
• The risk of symptomatic brain haemorrhage was
higher in the alteplase treated group (6.4%)
compared to the placebo group (0.6%)
• Number needed to treat to avoid one death or
person permanently disabled = 9. 39
40
 Background to ECASS 3
• European Cooperative Acute Stroke Study
• Thrombolysis was approved by EMEA in 2002
• 2 requests; Safe Implementation of
Thrombolysis in Stroke Monitoring
Study(SITS-MOST)
• ECASS 3 to extend therapeutic window

41
 ECASS III:Methodology
• ECASS III was double blind, parrellel-group,
multi-centred trial.
• Inclusion criteria:18-80 years of age
• Primary outcome:End points were BI and MRS.
• Original protocol:0.9mg/kg (max 90 mg) within
3-4 hrs; started in 2003
• Protocol amended with extension to 4.5 hrs after
pooled ECASS, ATLANTIS & NINDS rt-PA
stroke trials & slow recruitment in 2005
Lancet 2004;363:768-74
42
NEJM 1995 NEJM 2008

43
Concomitant Medications
• Antiplatelet & • Identical protocol
anticoagulants were • S/C heparin allowed
not allowed for 24 hrs (<10000 u) or
equivalent for low-
molecular-weight
heparin as
prophylaxis against
deep venous
thrombosis

44
Results
NINDS ECASS III

Total n=624; n=821: 418 rt-PA

Part 1 n=291
• ?rt-PA:Early clinical activity
• Outcome measure: Clinical
activity at 24 hours:4 points
improvement in NIH scale or
resolution of deficit in 24 hrs
• No significant difference
between rt-PA & placebo
• Benefit seen in 3 months
403 placebo
10% treated at 3-3.5 hrs
46.8% at 3.5-4.0 hrs
39.2% at 4-4.5 hrs
Median time 3 hrs 59 min
52.4% vs 45.2%
Odds ratio:1.34;95% CI,1.02-
1.76;p=0.04
MRS 0-1 compared
to placebo

Global stats for MRS,BI,NIHSS

Part 2 n=333 Odds ratio 1.28;95% CI 1.00-
• n=333 1.65; p<0.05

• Combined using a global

endpoint
The odds ratio for good
outcome at 3 months was 1.7
(95% CI 1.2-2.6)
45
Recent update MR.CLEAN
trial:Nov 2014
MR CLEAN study Dec 2014
Stroke Units

• Organised stroke care reduces mortality and

increases the proportion of patients making full
functional recovery
• Reduces death & dependency by 56 per 1000
patients treated
• Stroke unit triallist’ collaboration noted divergence
between stroke and general medical groups within 72
hours of admission
• High temperature, low diastolic blood pressure & high
blood glucose have detrimental effects on clinical
stroke
48
 Long Term Effects of Stroke
Unit

• Long Term Effects of Stroke Unit

Indredavik et al Stroke 1999. 30;1524-7

110 Stroke Units & 110 General Ward; 5

years on
* At home:21(19.1%) vs 9 (8.2%)
* Dead: 83(75.5%) vs 96(87.3%)
* Barthel Index >60 :22(20%) vs 9(8.2%)
49
50
51
52
 Platelet emboli

• Embolic material
from very early
thrombus
• Effects usually
seen in transient
ischaemic attack
(TIA) or acute
stroke

In early stages of thrombosis, endothelial cell

damage exposes collagen & attracts platelet plug,
fibrin forms on top and produces a fibrin & platelet
mesh
 Red clots form in regions where
there is stagnation; fibrin &
erythrocyte rich; cardiac
chambers, dilated atrium
etc….anticoagulation better
here.

L.Caplan Cerebrovascular Disease 2006

 Therapeutic
Options:Anti-platelet

• The aim of therapy is to prevent thrombus formation

by inhibiting platelet aggregation.
• Antiplatelet therapy has been shown to reduce the
odds of serious vascular events.
• Three main classes of anti-platelet drug:
• Cyclo-oxygenase inhibitors (e.g. aspirin, trifusal)
• Thienopyridine derivatives (e.g. clopidogrel
and ticlopidine)
• Phosphodiesterase inhibitors (e.g. cilostazol,
dipyridamole)
 Antiplatelet Drugs
• Aspirin: combined • Prevents early recurrent
ischaemic stroke of any type
data from IST,CAST
• Reduces death and disability
at 3-6 months
• Aspirin at 150-
• Increases the proportion of
300mg within 48 patients making a full
hours of stroke functional recovery
• Significant reduction in odds
of pulmonary embolism:
1 pulmonary embolism
avoided for every 1000
patients
 Dosage of Aspirin

• Aspirin in doses ranging from 50 to 1300 mg/d is

efficacious for preventing ischemic stroke after stroke
Higher doses of aspirin >100 mg have been
associated with a greater risk of gastrointestinal
hemorrhage.
Serebruany VL, Steinhubl SR et al Analysis of risk of bleeding
complications after different doses of aspirin in 192 036 patients enrolled
in 31 randomised controlled trials Am J Cardiol 2005;95:1218-1222

Increased odds of symptomatic intracranial:

haemorrhage(ICH)
Absolute terms 2 ICHs for every 1000 patients treated
 Antiplatelet Drugs
• Ticlopidine
(Thienopyridine derivatives)
• Canadian-American
Ticlopidine
study(CATS); 23% risk
reduction
• TASS(Ticlopidine
Aspirin Stroke Study)
47% risk reduction
compared to aspirin
• Neutropenia & diarrhoea
as side effect
• Dosage: 250 mg bd
 Anti-platelet Drugs
• Aspirin(50-325 mg od) • Evidence:ESPS-2(1996)
study; a randomised double
and dipyramidole blind placebo controlled trial of
SR(200 mg bd) is an ASA 25 mg bd and of
acceptable combination sustained-release DP 200 mg
bd
for stroke
• Dipyridamole and aspirin were
equally effective on their own
• In combination, there was a
37% risk reduction (p<0.001)
• Almost identical rates of
bleeding events in both arms
of the trial,
 Antiplatelet Drugs
• CAPRIE trial(2000)
• 19185 patients with
• Clopidogrel recent myocardial
infarction, ischaemic
• Thienopyridine:Platelet stroke or peripheral
adenosine diphosphate arterial disease were
receptor antagonist randomised in two
arms
• At follow up of 1.9 yrs,
overall RRR of 8.7%
was noted compared to
active control of aspirin
against ischaemic
stroke
 Dosage of Aspirin

• Aspirin in doses ranging from 50 to 1300 mg/d is

efficacious for preventing ischemic stroke after stroke
Higher doses of aspirin >100 mg have been
associated with a greater risk of gastrointestinal
hemorrhage.
Serebruany VL, Steinhubl SR et al Analysis of risk of bleeding
complications after different doses of aspirin in 192 036 patients enrolled
in 31 randomised controlled trials Am J Cardiol 2005;95:1218-1222

Increased odds of symptomatic intracranial:

haemorrhage(ICH)
Absolute terms 2 ICHs for every 1000 patients treated
 Anti-platelet Drugs
• Aspirin(50-325 mg od) • Evidence:ESPS-2(1996)
study; a randomised double
and dipyramidole blind placebo controlled trial of
SR(200 mg bd) is an ASA 25 mg bd and of
acceptable combination sustained-release DP 200 mg
bd
for stroke
• Dipyridamole and aspirin were
equally effective on their own
• In combination, there was a
37% risk reduction (p<0.001)
• Almost identical rates of
bleeding events in both arms
of the trial,
 Antiplatelet Drugs
• CAPRIE trial(2000)
• 19185 patients with
• Clopidogrel recent myocardial
infarction, ischaemic
• Thienopyridine:Platelet stroke or peripheral
adenosine diphosphate arterial disease were
receptor antagonist randomised in two
arms
• At follow up of 1.9 yrs,
overall RRR of 8.7%
was noted compared to
active control of aspirin
against ischaemic
stroke
 Cilostazol for prevention of secondary
Stroke: CSPS 2 Study
Lancet Neurology 2010
• Findings:
• Results: Primary end
• Dec 2003-2007, 2757
patients with non point 2.76% in cilostazol
cardioembolic ischaemic group & 3.71% in aspirin
strokes were enrolled; group (Hazard ratio
allocated cilostazol 100 mg
bd vs aspirin 81 mg daily 0.743, 95%CI 0.564-
• Primary endpoint; first 0.981; p=0.0357)
occurrence of
stroke(infarction)
• Pre-defined margin of non- • Less haemorrhage in
inferiority (upper 95% CI cilostazol group c/w
limit hazard ratio of 1.33)
aspirin
 ESPS 2 Study

Purpose & Design Patients & Follow up

• Low-dose aspirin and • 2 years

modified-release
dipyridamole alone or in • 6602 patients (1649
combination in the aspirin alone, 1654
secondary prevention of dipyridamole alone, 1650
ischaemic stroke, aspirin plus dipyridamole,
1649 placebo),with TIA or
• Randomised, double- ischaemic stroke < 3
blind, placebo-controlled, months
2 × 2 factorial
 ESPS 2 Study
Results Results II
Combination therapy • Relative risk reductions
significantly reduced the compared to placebo
incidence of stroke, were 11.1-27.6% in the
death, stroke and/or aspirin group, 8.0-18.7%
death, and other vascular in the dipyridamole group
events in each age and 20.3-45.2% in the
group.. combination group
• The time to recurrent
stroke was longest in the
combination therapy
group (p = 0.057
Meta-analysis for aspirin + dipyridamole
vs aspirin alone
ATRIAL FIBRILLATION
AND STROKE

NEW
TREATMENTS
New oral anticoagulants

These slides are for scientific and educational presentations only and are the copyright of Bayer
HealthCare AG
Local medical, legal and regulatory approval is required prior to external use
Rivaroxaban is not licensed for use in stroke prevention in patients with atrial fibrillation and nothing
contained within this slide set shall be construed as promoting its use in unlicensed indications
Bayer HealthCare AG shall not be liable for any damages caused by the use of these slides or parts
thereof
Bayer HealthCare AG does not accept responsibility and shall have no liability for miscommunication of
these data if these slides are changed in any way
The information provided is current as of January 2011
 Which studies have reported
data?

ROCKET RE-LY AVERROES ARISTOTLE ENGAGE

AF AF TIMI 48

Published Published Results Published Study

2011 20092 presented at 2011 ongoing
ESC 20103 expected
2012
 Comparison of the pharmacological
oral anticoagulant
characteristics of newer OACs
Parameter Dabigatran Rivaroxaban Apixaban Edoxaban
Target Thrombin Factor Xa Factor Xa Factor Xa
Oral bioavailability 6.5% 80–100%* ~66% 50%
Plasma protein 34–35% 92–95% 87% 40–59%
binding
Dosing (for SPAF Fixed, twice Fixed, once Fixed, twice Fixed, once
indication) daily daily daily daily
Prodrug Yes No No No
5–9 (young
Half-life (h) 12–14 healthy) 8–13 9–11
11–13 (elderly)
Tmax (h) ~6 2–4 1–3 1–2
Routine coagulation No No No No
*After oral ingestion
monitoring
*15–20 mg to be taken with food
Eriksson BI et al, 2011; Frost et al, 2007; Kubitza D et al, 2005; Kubitza D et al, 2005; Ogata K et al, 2010; Stangier et al,
2005; Raghavan N et al, 2009; Xarelto SmPC 2011; Xarelto PI 2011; Pradaxa SmPC 2011; Eliquis SmPC 2011;
Dabigatran PI; ROCKET AF Investigators 2010; Lopes et al, 2010; Ruff et al, 2010.
72
 Comparison of the pharmacological
characteristics of new OACs

Parameter Dabigatran Rivaroxaban Apixaban Edoxaban

Renal clearance 80% 33%; ~25% 35%
additional
33% cleared
after
metabolic
degradation
to inactive
drug
Potential drug Rifampicin, Potent Potent Potent
interactions quinidine, inhibitors of CYP3A4 inhibitors of
amiodarone, both CYP3A4 inhibitors* both CYP3A4
potent P-gp and P-gp*, and P-gp
*CYP, cytochrome P-450 isoenzymes; P-gp, P-glycoprotein. Strong inhibitors of both CYP3A4 and
Pgp include azole antifungals inhibitors strong
(e.g., ketoconazole, itraconazole, voriconazole, posaconazole) and
protease inhibitors, such as ritonavir. inducers of
CYP3A4

Eriksson BI et al, 2011; Xarelto Summary of Product Characteristics 2011.

 Lipids in Secondary Stroke
Prevention
• Statins have been proven to reduce
vascular events including ischaemic
strokes in subjects with previous strokes
• LDL cholesterol reduced by 50% or a
target less than 70 mg/dL(1.8 mmol/L)
• SPARCL trial recruited ischaemic stroke
patients with LDL 100-180 mg/dL.; 80
mg atorvastatin reduced recurrent stroke
by 16%
 Lipids in Secondary Stroke
Prevention
• Milionis et. al. Neurology 2009;72(21):1816-
22; 10 year risk reduction for recurrent stroke
in a retrospective observational analysis
linked to Athens Stroke Registry
• Pravastatin reduced strokes in patients with
coronary artery disease by a 32% relative risk
reduction [ CARE study; Plehn JF et al
Circulation 1999;99(2):216-23]
• British Heart Study; 25% reduction in risk of
stroke with simvastatin 40 mg; independent of
baseline serum cholesterol over 5 yrs
 Timing of Evaluation is
Vital
• The etiology of stroke may vary
depending on the practice of centers
managing stroke patients
• Timing of investigations (May be
reversible such as cardiac thrombus &
vegetations)
• Limitation of resources & lack of
expertise or manpower to routinely
perform more specialized investigations
such as TEE and TCD
 Pharmacology of
Phosphodiesterase(PDE) inhibitors

• Dipyridamole PDE type 5 inhibitor specific for guanosine

monophosphate mechanism:
• inhibits red blood cell uptake of adenosine, phosphodiesterase
inhibition leads to increased cyclic-3,5-adenosine
monophosphate within platelets, inhibits thromboxane A2
formation; decreasing platelet activation.
• Cilostazol PDE type 3 inhibitor specific for guanosine
monophosphate
• Vasodilators
• Other pleotropic effects including anti-atherogenic,
endothelial protection & anti-inflammatory effects
 Cilostazol in Ischaemic Stroke
• Cilostazol Stroke Prevention Study : 2000; n~1000
• Reduced recurrent strokes in a placebo-controlled double blind
trial. No change in bleeding complications between placebo &
cilostazol
• TOSS(Trial of Cilostazol in Symptomatic Intracranial Stenosis) 2005;
n=135
• Aspirin & cilostazol 200mg daily vs aspirin alone reduced
progression of intracranial arterial stenosis compared with
placebo; studied with TCD & MRA; large drop-out rate in both
groups
• TOSS 2 (in progress)
• Cilostazol Aspirin Therapy in Recurrent Stroke in
patients with Intracranial Arterial Stenosis(in progress)
Cilostazol Stroke Prevention
Study
 Anticoagulation

• Oral anticoagulation (INR 2.0-3.0)

reduces the risk of recurrent stroke in
patients with non-valvular AF (whether
permanent, chronic or paroxysmal type)
& most other cardiac sources of emboli
• Oral anticoagulation after non-cardiac
ischaemic stroke is not superior to
aspirin, complicated by excess bleeding

ESO Guidelines 2008

 Anticoagulation
Optimal time point when to start oral anticoagulation?
After TIA or minor stroke: immediately
Major stroke with significant infarction upon
neuroimaging (e.g. above a third of the MCA territory)
one should wait for some (e.g. 4) weeks. However,
this decision has to be individualized.
• In patients with AF and stable coronary disease,
aspirin should not be added to oral anticoagulation
• Anticoagulation should be taken long term or for at
least 3 months after cardioembolic stroke due to MI
CHADS VASC score
 Risk Factors associated with bleeding
during anticoagulation for atrial fibrillation
• Age> 75 years
• Antiplatelet drug use
• Uncontrolled hypertension
• History of bleeding or ICH
• Anaemia
• Polypharmacy
• Psychosocial: Poor memory, compliance
• Co-morbidities: uncontrolled epilepsy
 Ischemic Stroke/TIA
(TOAST classification)

• Large Vessel Atheroclerotic

Antiplatelet
• Small vessel(subcortical)
Antiplatelet
 Ischemic Stroke/TIA
(TOAST classification)
• Cardioembolic
Infective endocarditis: None
• Persistent/Paroxysmal AF
Anticoagulation (INR 2.0-3.0) long term
• Rheumatic mitral valve disease
Anticoagulation (INR 2.0-3.0) long term
• Bioprosthetic heart valve
Anticoagulation (INR 2.0-3.0) long term
 Ischemic Stroke/TIA
(TOAST classification)
Cardioembolic
• Mechanical heart valve
Anticoagulation (INR 2.5-3.5) long term
• Acute MI with LV thrombus:
Anticoagulation (INR 2.0 – 3.0) for 3 to 6 mths, then
switch to antiplatelet
• Dilated cardiomyopathy
Antiplatelet or anticoagulation
 Management of Ischemic Stroke
Clinical Practice Guidelines

http://www.neuro.org.my

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