How should recently symptomatic patients be treated urgent cea or cas

HHow Should Recently Symptomatic ow Should Recently Symptomatic Patients Be Treated: Urgent CEA Patients Be Treated: Urgent CEA oror CAS CAS

Tankut Akay Tankut Akay

14th Congress of Asian Society for Vascular & 16th 14th Congress of Asian Society for Vascular & 16th Congress of Turkish Society for Vascular and Congress of Turkish Society for Vascular and Endovascular Surgery & 8th Asian Venous ForumEndovascular Surgery & 8th Asian Venous Forum

Each year 120,000 people suffer 1st stroke in UK, 750,000 in US Within 1 year 33% dead

Less in Asian countries (9-30%)

most common cause of permanent disability, thesecond most common cause of dementia,

3rd most common cause of death

Symptoms due to:- Critical Stenosis- Occlusion- Unstable plaque

Stroke

Aetiology of StrokeAetiology of Stroke Ischaemic (80%)Ischaemic (80%)

- 75% Carotid territory- 75% Carotid territory- - 50% thrombo-embolism of ICA or 50% thrombo-embolism of ICA or

MCAMCA- 25% small vessel disease- 25% small vessel disease- 15% cardiac embolus,- 15% cardiac embolus,- 10% other: Takayasu’s arteritis, FMD- 10% other: Takayasu’s arteritis, FMD

- 15% Vertebrobasillar features- 15% Vertebrobasillar features- 10% unknown- 10% unknown

Haemorrhagic (20%)Haemorrhagic (20%) Under-perform by 2-3 fold CEA/CAS

Natural history of severe Natural history of severe symptomatic and asymptomatic symptomatic and asymptomatic

carotid artery stenosiscarotid artery stenosis

50

60

70

80

90

100

Golledge J, Greenhalgh RM, Davies AH. Stroke 2000

6 12 18

Time (months)

Freedom from ipsilateral stroke (%)

ACAS (60-99%)

ECST symptomless vessel (70-99%)

ECST (80-99%)

NASCET (70-99%)

Life-table analysis of stroke Life-table analysis of stroke related to presentationrelated to presentation

0102030405060708090

100

0 6 12 18 24 30 36

AmaurosisTIATransient strokeEstablished strokeProgressive strokeCrescendo TIA

Avoidance of stroke (%)

Time (months)

Golledge J, Cuming R, Beattie DK,

Davies AH, Greenhalgh RM JVS 1996

Life-table analysis of survival Life-table analysis of survival related to presenting symptomrelated to presenting symptom

0102030405060708090

100

0 6 12 18 24 30 36

AmaurosisTIATransient strokeEstablished strokeProgressive strokeCrescendo TIA

Survival (%)

Time (months)

Golledge J, Cuming R, Beattie DK, Davies AH, Greenhalgh RM

JVS 1996

The goals of early intervention;

•improving overall cerebral perfusion,

•reducing cumulative neuronal loss by restoring blood flow to the ischaemic penumbra,

•preventing early progression towards thrombosis

•removing a source of ongoing embolism.

1. neurological symptomatology,

2. degree of carotid stenosis,

3. medical co-morbidities,

4. vascular and local anatomical features

5. carotid plaque morphology.

Recently symptomatic? (TIA? Disabling stroke?Stroke in evolution?)

When to make an intervention , TIME?

How to make an intervention , CEA or CAS?

Recent TIA : a single episode of TIA, which occurred within 24 hr,

Crescendo TIA: two or more episodes within 24 h, with complete recovery after each episode.

Stroke in evolution: progression of a neurological deficit that had occurred over at least 24 h

Recent stroke : a fixed neurological deficit occurring within the past 5 days.

Minor stroke: any neurological event lasting more than 24 h with recovery in several days without residual functional impairment.

Major non-disabling stroke : any neurological event lasting more than 24 hr with minimal residual neurologic deficit

Terminology and target patient pool

Modified Rankin Score

0 - No symptoms.

1 - No significant disability. Able to carry out all usual activities, despite some symptoms.

2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.

3 - Moderate disability. Requires some help, but able to walk unassisted.

4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.

5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.

6 - Dead.

WHY ADVOCATING DELAY? (BEFORE)

CEA or CAS performed too soon after an acute stroke might convert anonhemorrhagic lesion into a hemorrhagic one

İnduce an enlargement of the infarction zone

1.Combined role of surgery or endovascular intervention equipment, and thrombolysis in this situation.

2.The easier access to diagnostic modalities, (duplex, transcranial Doppler, IADS, MR, BT)

3.the organisation of the admission wards into acute stroke units staffed by experienced personnel

4.A closer cooperation between vascular surgeons, radiologists, neurologists and stroke physicians have facilitated identification of neurologically unstable patients who may benefit from urgent carotid surgery or CAS ???

What has changed?

Risk of StrokeRisk of Stroke

Naylor 2007

TIME IS BRAIN

Number of stNumber of strrokes saved at 5 yearsokes saved at 5 yearsPer 1000 CEAs in 50-99% stenosis

Naylor 2007

Benefit of Urgent TreatmentBenefit of Urgent Treatment

Naylor 2007

Comment: the longer the patient waits for the procedure, the less effective is the procedure, as a cohort of patients would be affected by stroke prior to CEA.

Delaying intervention quite probably means that patients are better selected, and this could guarantee better early outcomes, but this delay can also resultin an interval stroke rate of 9 to15 %

GERTLER JP, BLANKENSTEIJN JD, BREWSTER DC, MONCURE AC, CAMBRIA RP, LAMURAGLIA GM et al. Carotid endarterectomy for unstable and compelling neurologic conditions: do results justifyan aggressive approach? J Vasc Surg 1994;19:32e40.

ABCD criteria for predicting very early stroke risk

ROTHWELL PM, GILES MF, FLOSSMAN E, LOVELOCK CE, REDGRAVE JN, WARLOW CP et al. A simple score (ABCD) to identify individuals at high early risk of stroke after transient ischaemic attack. Lancet2005;366:29e36.

median time from symptoms to surgery was shown to be 189 days in the UK national carotid audit (1997).

2004 Royal College of Physicians Sentinel Stroke Audit also found

that only 50% of patients had undergone a duplex scan within 12 weeks of their initial event

median delay to surgery was 80 days in GALA trial

232 CEA between 2004-2013

167 Symptomatic undergone CEA

Mean time to surgery 4.8 weeks ± 1.7

All with local anesthesia and selective shunt

Mortality 3.6 %

Major stroke 2.3 %

Minor stroke 4.7 %

Follow up: 2.3 years ±1.8

Late stroke : 1.8 %

•why is there such a discrepancy between national/ international recommendations and “real world” practice?

•Are we operating ‘low risk for stroke’ patients, while the really ‘high risk’ patients suffer strokes with little chance of undergoing any intervention.

(i) CEA should be delayed for 6-8 weeks after a stroke because of the increased risk of haemorrhagic transformation of the infarct, i.e. emergency surgery was dangerous,

(ii) early/expedited surgery (in general) was probably associated with an increased rate of complications, so why expose yourself to unnecessary medico-legal risk

(iii) the risk of suffering a stroke in the first few weeks after presentationwas probably not really that high

(iv) early symptom resolution was generally taken to be a sign thaturgent investigation/treatment was unnecessary

Old Habits

Interpretation: A little bit of delay in the system probably does no real harm and might, actually, be beneficialto the patient (and possibly to the surgeon regarding published risks).

Outcome: No professional impetus to change the way the system works

CEA may be performed as early as 2 week after acute stroke, with acceptable results in patientswith mild to moderate preoperative neurologic deficits.

Early carotid endarterectomy isnot recommended for patients with disabling strokeor large infarction and/or brain oedema on CT scanning(Grade C recommendation).

SPREAD. Stroke prevention and educational awareness diffusion. 2007.

CASCAS

The main concern about CAS in urgent cases is that while with CEA the plaque is completely removed, after stenting it is only remodelled and its stabilizationis essential to avoid later embolic events.

CEA or CAS ?

studies

30 Day Stroke or Death Rate30 Day Stroke or Death Rate

0

1

2

3

4

5

6

7

8

9Angioplasty

Endarterectomy

Any stroke

or death

Disabling stroke

or death

%

Golledge J, Mitchell A, Greenhalgh RM, Davies AH Stroke 2000

30 Day Stroke Rate30 Day Stroke Rate

0

1

2

3

4

5

6

7

8

Angioplasty

Endarterectomy

Any stroke Disabling/

fatal stroke

TIA Death

%

Golledge J, Mitchell A, Greenhalgh RM,

Davies AH Stroke 2000

3 large European randomized controlled trials comparing CAS with CEA in SYMPTOMATIC patients at average risk for surgery:

EVA-3S (Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Artery Stenosis-3S)

SPACE (Stent-Supported Percutaneous Angioplastyof the Carotid Artery versus Endarterectomy

ICSS (International Carotid Stenting Study)

EVAS -3EVAS -3 RCTRCT N=527N=527

Stoke/Death RatesStoke/Death Rates 30 day 30 day CEA 1.5 % vs CAS 3.4% CEA 1.5 % vs CAS 3.4% RR 2.2RR 2.2

6/126/12 CEACEA 6.1% vs CAS 11.7% 6.1% vs CAS 11.7% p<0.02p<0.02

4 yrs4 yrs CEA 6.2% vs CAS 11.1% CEA 6.2% vs CAS 11.1% RR 1.97RR 1.97p<0.03p<0.03

Mas et al, 2006 ,2008Mas et al, 2006 ,2008

2009

What about USA ?

Between 2003 and 2004, an estimated 259,080 carotid revascularization

For symptomatic patients (8%), the rates for postoperative stroke (4.2% vs 1.1%, P < .0001) and mortality (7.5% vs 1.0%, P < .0001) were significantly higher after CAS

Carotid endarterectomy was performed with lower stroke and death rates than carotid artery stenting in the United States in 2003 and 2004.McPhee JT, Hill JS, Ciocca RG, Messina LM, Eslami MH.J Vasc Surg. 2007 Dec;46(6):1112-1118.National trends in utilization and postprocedure outcomes for carotid artery revascularization 2005 to 2007.Eslami MH, McPhee JT, Simons JP, Schanzer A, Messina LM.

Ten trials encompassing 3580 patients were analyzed.

CAS had a higher risk of 30-day stroke/death than CEA (risk ratio [RR], 1.30; 95% CI, 1.01-1.67).

Subgroup analysis of trials enrolling only SYMPTOMATİC patients showed higher risk of 30-day stroke/death (RR, 1.63; 95% CI, 1.18-2.25), but trials enrolling both symptomatic and asymptomatic patients showed no significant differences (RR, 0.89; 95% CI, 0.59-1.35).

Brahmandam et al 2008

WHY CEA WAS FOUND TO BE SUPERIOR?

Accepting inexperienced CAS operators compared with established CEA operators;

Performing CAS without embolization protection devices (EPD)

CREST

Changed the attitude?

CREST Study DesignCREST Study Design RCT of CAS vs CEARCT of CAS vs CEA 108 centers in US and 8 centers in Canada108 centers in US and 8 centers in Canada 1:1 randomisation, stratified by centre and 1:1 randomisation, stratified by centre and

symptomatic statussymptomatic status

Primary end-point – composite:Primary end-point – composite:• Any stroke, MI (including biochemical) or death Any stroke, MI (including biochemical) or death

within 30 dayswithin 30 days• Ipsilateral stroke to 4 yearsIpsilateral stroke to 4 years

Target recruitment 2,500Target recruitment 2,500 Industry sponsoredIndustry sponsored

CREST

symptomatic (n=1,321) or asymptomatic (n=1,181)

At 30 days, the rate of stroke was significantly higher with stenting, at 4.1% vs. 2.3% with surgery.

Myocardial infarction was higher with carotid endarterectomy, at 2.3% vs. 1.1% with stenting.

when death and stroke are considered alone, there are almost twice as many events with carotid stenting/angioplasty as there are with carotid endarterectomy.

For symptomatic patients, the periprocedural stroke and death rates were 6.0% 0.9% for CAS and 3.2%0.7% for CEA (HR 1.89; 95% CI 1.11-3.21; P 0.02)

“I do not believe the results of CREST should change the conclusion that endarterectomy remains the treatment of choice for symptomatic patients”

NEJM 2010;363(1):11-23

NEJM 2010;363(1):11-23

CREST at 4 YearsCREST at 4 Years

CREST LimitationsCREST Limitations Composite endpointComposite endpoint Biochemical MIBiochemical MI Underpowered to show difference in death and major Underpowered to show difference in death and major

ipsilateral strokeipsilateral stroke Heterogeneity of symptomatic and asymptomatic patientsHeterogeneity of symptomatic and asymptomatic patients Not all patients on statins Not all patients on statins More lipid lowering in CEAMore lipid lowering in CEA More anti-platelets in CASMore anti-platelets in CAS Advances in BMT, CEA stent and embolic protection since Advances in BMT, CEA stent and embolic protection since

CREST commenced in 2000CREST commenced in 2000 Can CREST CAS results be reproduced in wider practice?Can CREST CAS results be reproduced in wider practice? Left to interpretation based on personal bias?Left to interpretation based on personal bias?

Carotid Artery Stenting in Recently Symptomatic Patients: A Single Center ExperienceCarlo Setacci , Gianmarco de Donato, Emiliano Chisci, Francesco Setacci

2006 to 2008, 43 patients with symptomatic carotid stenosis

minor stroke - deferred CAS, (treatment within 1 to 30 days from the onset of symptoms, according to the stabilization of cerebral symptoms

mean time, 6.5 days; range, 2 to 28 days

cerebral protection device

The new adverse events in the TIA patients at 1 month were 1 non-neurological death (3.8%) and 1 TIA (3.8%).

In the minor stroke group, at 1 month, 10 of 17 patients (58.8%) experienced an improvement), while in 35.3% of patients did not.

GUIDELINES ??

Better out than in !Better out than in !

Take home messages

If patient is suitable for CEA CEA

IF NOT ??

If performed by experienced hands at experienced centers, CAS is an acceptable alternative to CEA, particularly for patients who are at high surgical risk or unsuitable anatomy

•additional medical therapy may prove to be an important adjunct to surgery.

CAS and CEA are complementary procedures with their own limitations in themselves.

Cardiac evaluation is mandatory.

Apart from systemic heparinisation, other therapeutic options, the transcranial Doppler-directed Dextran therapy and the free-radical scavengers

Define and analyze the neurological status

A custom made treatment option depending on each patient’s status

If patient is suitable for CEA, perform CEA, if not CAS

Considering that a 30-day death/stroke risk of 8% is acceptable if CEA is performed within 2 weeks of the index event, reducing this threshold of acceptable risk to 6% if surgery is performed between 2-4 weeks and down to 4% if CEA is delayed beyond 4 weeks.

DONT BE LATE , it will make a GREAT difference in someone’s life !!!