Interventions for Stroke prevention

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Interventions for Stroke prevention

• When, who, what?

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Topics to cover

• Treatment of carotid stenosis
• Treatment of PFO
• Not
• Medical management
• AF management

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Ischaemic stroke

• Atherothromboembolism 50
• Small vessel disease 25
• Cardioembolism 20
• Other rarities 5

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Carotid stenosis is major cause of CVA

• Recent symptoms
• 28 2-year risk CVA
• carotid stenosis gt80
• 0.3-2.4 of population

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Who to treat?

• Symptomatic carotid stenosis
• Asymptomatic carotid stenosis
• Pre CABG

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Pre-requisites for success

• Prove surgery is better than tablets
• Prove percutaneous approach is almost as good as
  surgery
• Add stents/adjunctive therapy to make
  percutaneous BETTER THAN surgery

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Prove surgery is better than tablets

• Eastcott/ Debakey 1953 CEA
• Symptomatic
• NASCET (659)
• gt70 stenosis
• 2-yr fu CVA 9 vs 26 on medical Rx
• ECST (3024)
• gt60 stenosis
• 3-yr fu CVA 14.9 vs 26.5 on medical Rx
• Asymptomatic
• ACAS
• gt60 stenosis
• 5-yr fu CVA 5.1 vs 11 on medical Rx
• ASCT
• gt80 stenosis
• 5 year fu CVA

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How severe a stenosis?

• Asymptomatic
• gt80
• Symptomatic
• gt70 on angio
• Possibly lower (US 50)

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Quantify the risk of the procedure

• Asymptomatic stenosis
• 60 stenosis
• Medical Rx CVA/death 2.2 1 year
• CEA CVA/death 3 30 day
• gt80
• Medical Rx CVA/death 5.5 1 year
• CEA CVA/death 4.6 30 day

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Choose your surgeon

• Stroke/death lt3 in asymptomatic patients
• Does it regularly
• CEA is a great operation
• BUT..

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recurrent hemisspheric TIAhigh grade ICA
stenosis
pre
post
Carotid Wallstent 9.0/30 mm
O.L. 1148/99
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Prove percutaneous approach is almost as good as
surgery

• CAVATAS
• Randomisation 1992-1997
• 560 pts
• 504 PTA vs surgery
• 86 stenosis
• Only 55 stents used
• One CVA at time of stent.

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CAVATAS
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World wide CAS
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Why have a stent program?

• CEA tricky
• Restenosis
• Not C2-C7
• Hostile neck
• RT
• Surgery
• Scars
• High risk
• Medical Morbidity
• Neuro Morbidity
• RLN palsy contralat

• CAS
• Minimally Invasive
• No scar
• No GA Easy
• Equivalent
• Treatment of occlusion post CEA

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The real life data

• CAS (World registry)
• Mortality 1
• LOS 1.8d
• Death/Stroke risk 3
• Death/stroke risk
• 1.8-2.8

• CEA (VSSGBI)
• Mortality 1.3
• LOS 3.9d
• Death/Stroke risk 3

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Sapphire Trial
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Results at 30 days
MAEdeath/MI/CVA
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Sapphire trial 1 year data
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Choose your procedure?
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Flanders study
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And Now?

• German trial
• French Trial
• Doubt about safety of CAS

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EVA-3S (NEJM 2006)

• French, Prospective, Randomised
• Hypothesis
• CAS not inferior to CEA
• Symptomatic disease
• Assumed 30 day events
• CEA 5.6
• CAS 4
• Stopped
• Primary end point not reached
• Would require 4000 patients (527 randomised)

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EVA-3S (NEJM 2006)

• 30 day
• CEA CAS
• All stroke and death 3.9 9.6
• Disabling stroke and death 1.5 3.45
• Each surgeon
• 25 CEAs in the year before trial
• Interventionalist
• 5 CAS in total
• Introduction of protection
• Significant reduction in strokes
• Drug regime discretionary

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SPACE (Lancet 2006)

• Germany, Austria and Switzerland
• Hypothesis
• CAS not inferior to CEA
• Symptomatic, prospective, randomised
• Assumed 5 event rate for both
• Plan for 900 patients in each group
• 25 of surgeons rejected on track record
• 1183 treated
• Estimated need for 2500
• Stopped
• Lack of funding

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SPACE (Lancet 2006)

• 30 day stroke and death rate
• CEA 6.34
• CAS 6.84
• CAS not more than 2.5 inferior to CEA
• 91 chance true
• 9 chance false
• Protection used in 25 of CAS patients

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Meta-analysis
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Endovascular vs Surgical treatment of Carotid
StenosisAny Stroke or Death at 30 days Random
effects method
Random Effects Model OR 1.44 CI 0.91 2.26Not
statistically significant
Ederle J et al. Cochrane Database of Systematic
Reviews in preparation
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Numbers of patients included in the meta-analysis
of Symptomatic Carotid Surgery Trials

• P Rothwell et al. Lancet 2003361107-116 Carotid
  surgery versus medical care
• Outcomes 3202 strokes deaths
• J Ederle at al. Cochrane Review in prep.Carotid
  surgery vs Endovascular treatment
• Safety outcomes 210 strokes deaths

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CAVATAS Intention to treat analysis Carotids
fit for surgery (n504) Events within 30 days of
treatment

• Event Endovascular
  Surgical
  treatment treatment
• All strokes/death 10.0 9.9 NS
• More than 7 days duration
• Myocardial infarction 0 0.8
  NS
• Cranial nerve palsy 0 8.7
  lt0.0001
• Haematoma 1.2 6.7 lt0.002
• requiring surgery or prolonging stay

Lancet 20013571729-1737
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Endovascular vs Surgical treatment of Carotid
Stenosis Any Stroke, Cranial Neuropathy or
Death at 30 days
Random Effects OR 0.61 CI 0.32 1.17Not
statistically significant
Ederle J et al. Cochrane Database of Systematic
Reviews in preparation
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Endovascular vs Surgical treatment of Carotid
StenosisDisabling Stroke or Death at 30 days
Fixed effects Model OR 1.22 CI 0.83 1.80Not
statistically significant
Ederle J et al. Cochrane Database of Systematic
Reviews in preparation
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Conclusion

• The carotid is 25 years behind the coronary
• It is catching up fast.
• Different vessel and vascular bed (cf diabetes)
• The multidisciplinary team
• We have a program up and running

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The present

• Symptomatic carotid stenosis gt70 (?50)
• CEA or CAS
• High risk, then CAS
• Get it done within 3 weeks
• Asymptomatic carotid stenosis gt80
• CEA or CAS
• High risk, then should you be doing it at all?
• Pre CABG
• Do one side if bilateral stenosis
• CAS would be a good choice

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Should we close holes in the heart?
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Cardiac Sources of Stroke

• 20 of neurological events may be cardiac
• 40 of neurological events are cryptogenic
• ? Are these often cardiac?
• Rheumatic heart disease
• AF
• Cardiomyopathy (clot)
• Aortic atheroma
• Patent Foramen Ovale

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Other investigations

• History suggestive of arrthymia, syncope, cardiac
  cause, cardio-embolic cause
• 12 lead ECG series , may identify PAF
• Look for postural hypotension
• 24 hour tape
• Echo (TTE)

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Who to investigate for PFO?

• Class I
• Any age visceral or peripheral embolism
• lt45 CVA
• gt45 CVA without risk factors for CVD
• Any age if decision re anticoagulation may
  change
• Class IIa
• Any age CVA with possible embolic cause

1564 Botali
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What do we need to know?

• How do we diagnose it?
• Is there a risk associated with PFO?
• Will the risk be reduced by medical therapy?
• Will the risk be reduced by closure?
• Is closure safe?

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Incidence

• Autopsy study n965
• PFO 27
• 34 lt30 20 gt80
• 3.4mm 5.8mm
• Echocardiographic surveillance studies
• PFO 8 (2-23)
• ASA 7.1 (3-12)
• MVP 8.9 (5-9)

Hagen et al 1984
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Diagnosis

• TransCranial Doppler 86
• Transthoracic Echo and contrast gt90
• TOE and contrast gt90
• Two modalities are better than one

Heckman et al
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LV
RV
LA
RA
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The risk of PFO and stroke

• Lechat et al agelt55 CVA
• Control PFO 10
• All CVA PFO 40 (plt0.001)
• Cryptogenic PFO 54
• Mas et al age 18-35 CVA
• All CVA PFO 36

NEJM 1988, 2001
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Meta-analysis

• CVA lt55 9 studies
• PFO OR 3.1 (2.3-4.2)
• ASA OR 6.1 (2.5-15)
• Both OR 15.6 (2.8-86)

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What do we need to know?

• How do we diagnose it?
• Is there a risk associated with PFO?
• Will the risk be reduced by medical therapy?
• Will the risk be reduced by closure?
• Is closure safe?

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Mechanism?

• Paradoxical embolism?
• Larger hole found in CVA pts vs non-CVA
• Residual shunt after closure predicts recurrence
• Divers brains and PFO
• In situ clot in tract?
• Predict atrial arrhythmias? (OR 4.1)
• Predict a hypercoagulable state?

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Medical Therapy

• What?
• Aspirin or Warfarin
• Comess et al n33 16 pa
• No Rx
• Mas et al n132 3.4 pa
• Aspirin or warfarin
• Lausanne registry 3.8 pa
• Aspirin or warfarin

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Device closure

• Meier et al
• CVA/TIA
• 6.6 pa No Closure
• 4.5 pa Closure
• Stroke risk
• 3 No Closure
• 0 Closure
• RCT awaited

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What do we need to know?

• How do we diagnose it?
• Is there a risk associated with PFO?
• Will the risk be reduced by medical therapy?
• Will the risk be reduced by closure? ?
• Is closure safe?

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Who to investigate?

• Class I
• Any age visceral or peripheral embolism
• lt45 CVA
• gt45 CVA without risk factors for CVD
• Any age if decision re anticoagulation may
  change
• Class IIa
• Any age CVA with possible embolic cause

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Problems

• Failure to deploy lt5
• Device embolisation 1
• Thrombus 1-5
• Death 0
• I quote 1 risk from procedure

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What do we need to know?

• How do we diagnose it?
• Is there a risk associated with PFO?
• Will the risk be reduced by medical therapy?
• Will the risk be reduced by closure? ?
• Is closure safe?

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Who to Close?

• None?
• All?

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Conclusion

• Closure may well reduce the risk of recurrence
  and should be considered within 3 months
• Divers and those with Migraine deserve special
  consideration also

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Conclusions

• Investigation and treatment essential
• Strokes time as a cinderella is over
• Worthwhile interventions are available (at a
  price)
• These are worthless without stopping smoking,
  lipids, BP control etc.

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Case 1

• 59 year old
• Loss of speech and weakness in right hand for 1
  hour
• No HT/DM/smoking/FH/Lipids/Renal
• No cardiac symptoms
• MRI confirms stroke
• Carotids OK

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Case 1

• Needs cardiac work-up to exclude
• PAF
• LAA clot
• PFO
• PFO found with large shunt.
• Close it?

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Case 2

• 52 year old
• One clinical episode of weakness in L arm
• No risk factors
• MRI shows 5 areas of infarction of similar age on
  left side
• Carotids OK bilaterally

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Case 2

• Needs investigation for
• PAF
• LAA clot
• PFO
• PFO found
• Should close this!

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Case 3

• 68 yr old
• Asian/HT/DM/IHD with CABG
• Recurrent TIAs with left sided weakness
• Carotids bilateral gt80 stenosis

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Case 3

• Need to exclude PFO, PAF?
• Need to treat R carotid urgently
• CEA
• CAS

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