How should recently symptomatic patients be treated urgent cea or cas

1. HHow Should Recently Symptomaticow Should Recently Symptomatic
Patients Be Treated: Urgent CEAPatients Be Treated: Urgent CEA oror CASCAS
Tankut AkayTankut Akay
14th Congress of Asian Society for Vascular & 16th14th Congress of Asian Society for Vascular & 16th
Congress of Turkish Society for Vascular andCongress of Turkish Society for Vascular and
Endovascular Surgery & 8th Asian Venous ForumEndovascular Surgery & 8th Asian Venous Forum

2. 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, the
second most common cause of dementia,
3rd most common cause of
death
Symptoms due to:
- Critical Stenosis
- Occlusion
- Unstable plaque
Stroke

3. Aetiology of StrokeAetiology of Stroke
 Ischaemic (80%)Ischaemic (80%)
- 75% Carotid territory- 75% Carotid territory
-- 50% thrombo-embolism of ICA or50% 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

4. Natural history of severeNatural history of severe
symptomatic and asymptomaticsymptomatic 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%)

5. Life-table analysis of strokeLife-table analysis of stroke
related to presentationrelated to presentation
0
10
20
30
40
50
60
70
80
90
100
0 6 12 18 24 30 36
Amaurosis
TIA
Transient stroke
Established stroke
Progressive stroke
Crescendo TIA
Avoidance of
stroke (%)
Time (months)
Golledge J, Cuming R, Beattie DK,
Davies AH, Greenhalgh RM JVS 1996

6. Life-table analysis of survivalLife-table analysis of survival
related to presenting symptomrelated to presenting symptom
0
10
20
30
40
50
60
70
80
90
100
0 6 12 18 24 30 36
Amaurosis
TIA
Transient stroke
Established stroke
Progressive stroke
Crescendo TIA
Survival (%)
Time (months)
Golledge J, Cuming R, Beattie DK,
Davies AH, Greenhalgh RM
JVS 1996

7. 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.

8. 1. neurological symptomatology,
2. degree of carotid stenosis,
3. medical co-morbidities,
4. vascular and local anatomical
features
5. carotid plaque morphology.

9. Recently symptomatic?
(TIA? Disabling stroke?Stroke in
evolution?)
When to make an
intervention , TIME?
How to make an
intervention , CEA or CAS?

10. 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

11. 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.

12. WHY ADVOCATING DELAY? (BEFORE)
CEA or CAS performed too soon after an
acute stroke might convert a
nonhemorrhagic lesion into a hemorrhagic
one
İnduce an enlargement of the infarction zone

13. 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?

14. Risk of StrokeRisk of Stroke
Naylor
TIME IS BRAIN

15. Number of stNumber of strrokes saved at 5 yearsokes saved at 5 years
Per 1000 CEAs in 50-99% stenosis
Naylor

16. Benefit of Urgent TreatmentBenefit of Urgent Treatment
Naylor 2007

17. 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.

19. Delaying intervention quite probably
means that patients are better selected,
and this could guarantee better early
outcomes, but this delay can also result
in 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 justify
an aggressive approach? J Vasc Surg 1994;19:32e40.

24. 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. Lancet
2005;366:29e36.

26. 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

27. 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 %

28. •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.

29. (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 presentation
was probably not really that high
(iv) early symptom resolution was generally taken to be a sign that
urgent investigation/treatment was unnecessary
Old Habits

30. Interpretation: A little bit of delay in the
system probably does no real harm and
might, actually, be beneficial
to the patient (and possibly to the surgeon
regarding published risks).
Outcome: No professional impetus to change
the way the system works

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

32. Early carotid endarterectomy is
not recommended for patients with
disabling stroke
or large infarction and/or brain
oedema on CT scanning
(Grade C recommendation).
SPREAD. Stroke prevention and educational
awareness diffusion. 2007.

33. CASCAS

37. 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 stabilization
is essential to avoid later embolic events.

38. CEA or CAS ?
studies

40. 30 Day Stroke or Death Rate30 Day Stroke or Death Rate
0
1
2
3
4
5
6
7
8
9
Angioplasty
Endarterectomy
Any stroke
or death
Disabling stroke
or death
%
Golledge J, Mitchell A, Greenhalgh RM, Davies AH Stroke 2000

41. 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

42. 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 Angioplasty
of the Carotid Artery versus Endarterectomy
ICSS (International Carotid Stenting Study)

43. EVAS -3EVAS -3
 RCTRCT
 N=527N=527
Stoke/Death RatesStoke/Death Rates
 30 day30 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 1.97
p<0.03p<0.03
Mas et al, 2006 ,2008Mas et al, 2006 ,2008

44. 2009

46. 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.

48. 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

49. WHY CEA WAS FOUND TO BE
SUPERIOR?
Accepting inexperienced CAS operators compared with
established CEA operators;
Performing CAS without embolization protection devices
(EPD)

51. CREST
Changed the attitude?

52. 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 and1:1 randomisation, stratified by centre and
symptomatic statussymptomatic status
 Primary end-point – composite:Primary end-point – composite:
• Any stroke, MI (including biochemical) or deathAny 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

53. 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”

54. NEJM 2010;363(1):11-23

55. NEJM 2010;363(1):11-23
CREST at 4 YearsCREST at 4 Years

56. CREST LimitationsCREST Limitations
 Composite endpointComposite endpoint
 Biochemical MIBiochemical MI
 Underpowered to show difference in death and majorUnderpowered 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 statinsNot 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 sinceAdvances 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?

57. Carotid Artery Stenting in Recently Symptomatic Patients: A Single Center
Experience
Carlo 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.

58. GUIDELINES ??

63. Better out than in !Better out than in !

65. 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.

66. 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

67. 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

68. 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.

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