NWLCSNGP DIPLOMA COURSE

2009

Agenda

Speakers

• Nick Peters• Prapa Kanagaratnam

• Richard Perry• Diane Ames• Harri Jenkins• Iqbal Malik

Interventions for Stroke prevention

When, who, what?

Iqbal MalikConsultant Interventional Cardiologist

2009

Topics to cover

• Treatment of carotid stenosis

• Treatment of PFO

• LAA closure

• Not– Medical management– AF management

Ischaemic stroke

• Atherothromboembolism 50%

• Small vessel disease 25%

• Cardioembolism 20%

• Other rarities 5%

Carotid stenosis is major cause of CVA

– Recent symptoms• 28% 2-year risk CVA

– carotid stenosis >80% • 0.3-2.4% of population

Who to treat?

• Symptomatic carotid stenosis

• Asymptomatic carotid stenosis

• Pre CABG

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

• Eastcott/ Debakey 1953 CEA

Symptomatic• NASCET (659)

– >70% stenosis– 2-yr fu CVA 9% vs 26% on medical Rx

• ECST (3024)– >60% stenosis– 3-yr fu CVA 14.9% vs 26.5% on medical Rx

Asymptomatic• ACAS

– >60% stenosis– 5-yr fu CVA 5.1% vs 11% on medical Rx

• ASCT– >80% stenosis– 5 year fu CVA

Prove surgery is better than tablets

How severe a stenosis?

• Asymptomatic– >80%

• Symptomatic– >70% on angio– Possibly lower (US 50%)

Quantify the risk of the procedure

• Asymptomatic stenosis– 60% stenosis

• Medical Rx CVA/death 2.2% 1 year• CEA CVA/death 3%

30 day

– >80%• Medical Rx CVA/death 5.5% 1 year• CEA CVA/death 4.6%

30 day

Choose your surgeon

• Stroke/death <3% in asymptomatic patients

• Does it regularly

• CEA is a great operation

• BUT…………..

recurrent hemisspheric TIA;high grade ICA stenosis

pre post

Carotid Wallstent™ 9.0/30 mmO.L. 1148/99

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.

CAVATAS

PTA Surgery p

30d death/CVA

10% 9.9% p=ns

CN palsy 0% 9% p<0.0001

Haematoma 1% 7% P=0.0015

MI 0% 0.8% ns

Re-stenosis 17% 5% P<0.0001

World wide CAS

Angioguard (Cordis)

Percusurge

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

The real life data

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

• CAS (World registry)– Mortality 1%

– LOS 1.8d

– Death/Stroke risk 3%

– Death/stroke risk

1.8-2.8%

All patient

s

High risk

patients

Sapphire Trial

Asymptomatic >80%Symptomatic >50%

n=747

Surgeon said non=409

Randomisedn=307

Stenter said non=7

Stent registry SAPPHIRE CEA registry

Stentn=156

CEAn=151

Results at 30 days

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

Total death/stroke

Stent

CEA

Registry

MAE=death/MI/CVA

Sapphire trial 1 year data

Choose your procedure?

Flanders study

Stenosis

Not suitable for CEA7.5%

Not suitable for CAS12.75%

CEA/CAS

Patient choice

CAS71%

CEA29%

And Now~?

• German trial• French Trial

• Doubt about safety of CAS

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)

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 CEA’s in the year before trial

• “Interventionalist”– 5 CAS in total

• Introduction of protection– Significant reduction in strokes

• Drug regime discretionary

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

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

Meta-analysis

Endovascular vs Surgical treatment of Carotid Stenosis:

Any Stroke or Death at 30 days – Random effects method

Ederle J et al. Cochrane Database of Systematic Reviews: in preparation

Random Effects Model: OR 1.44; CI 0.91 – 2.26Not statistically significant

Numbers of patients included in the meta-analysis of Symptomatic Carotid

Surgery Trials

• P Rothwell et al. Lancet 2003;361:107-116 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

CAVATAS Intention to treat analysis Carotids fit for surgery (n=504) Events within 30 days of treatment

Event Endovascular Surgical treatment

treatmentAll strokes*/death 10.0% 9.9%

NS* More than 7 days duration

Myocardial infarction 0% 0.8% NS

Cranial nerve palsy 0% 8.7% <0.0001

Haematoma† 1.2% 6.7% <0.002 †requiring surgery or prolonging stay

Lancet 2001;357:1729-1737

Endovascular vs Surgical treatment of Carotid Stenosis:

Disabling Stroke or Death at 30 days

Ederle J et al. Cochrane Database of Systematic Reviews: in preparation

Fixed effects Model: OR 1.22; CI 0.83 – 1.80Not statistically significant

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

The present• Symptomatic carotid stenosis >70% (?50%)

– CEA or CAS– High risk, then CAS– Get it done within 3 weeks

• Asymptomatic carotid stenosis >80%– 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

Should we close holes in the heart?

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

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)

Who to investigate for PFO?

• Class I– Any age visceral or peripheral embolism– <45 CVA– >45 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

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?

Incidence

• Autopsy study: n=965– PFO 27%– 34% <30 20% >80– 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

Diagnosis

• TransCranial Doppler 86%

• Transthoracic Echo and contrast >90%

• TOE and contrast >90%

• Two modalities are better than one

Heckman et al

LV

RA

RV

LA

The risk of PFO and stroke

• Lechat et al age<55 CVA– Control PFO 10%– All CVA PFO 40% (p<0.001)– Cryptogenic PFO 54%

• Mas et al age 18-35 CVA– All CVA PFO 36%

NEJM 1988, 2001

Meta-analysis

• CVA <55 9 studies

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

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?

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?

Medical Therapy• What?

– Aspirin or Warfarin

• Comess et al n=33 16% pa– No Rx

• Mas et al n=132 3.4% pa– Aspirin or warfarin

• Lausanne registry 3.8% pa– Aspirin or warfarin

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

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?

Who to investigate?Who to investigate?

• Class IClass I– Any ageAny age visceral or peripheral embolismvisceral or peripheral embolism– <45 <45 CVACVA– >45>45 CVA without risk factors for CVDCVA without risk factors for CVD– Any ageAny age if decision re anticoagulation may if decision re anticoagulation may

changechange

• Class IIaClass IIa– Any ageAny age CVA with possible embolic causeCVA with possible embolic cause

Problems

• Failure to deploy <5%• Device embolisation 1%• Thrombus 1-5%

• Death 0%

• I quote 1% risk from procedure

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? +

Who to Close?

• None?

• All?

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

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.

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 single stroke• Carotids OK• Thrombophilia- Anticardiolipin antibody

Case 1

• Needs cardiac work-up to exclude– PAF– LAA clot– PFO

• PFO found with large shunt.• Close it?

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

Case 2

• Needs investigation for:– PAF– LAA clot– PFO

• PFO found

• Should close this!

Case 3

• 68 yr old

• Asian/HT/DM/IHD with CABG

• Recurrent TIAs with left sided weakness

• Carotids bilateral >80% stenosis

Case 3

• Need to exclude PFO, PAF?

• Need to treat R carotid urgently– CEA– CAS

LAA closure

Protect AF

• Stroke, CVS death, systemic Embolisation• 707 patients rates per 100 pt yrs• CHADS score 1-3• Take warfarin for 6 weeks after (95% off it at 6

mo)

Watchman Warfarin

Death/CVA/

embolisation

3.0 4.9

All stroke 2.6% 3.5%

Bleed/PE/

Device gone

7.4 4.4