STROKE AND TIA - OPTIMAL SURGICAL
MANAGEMENT OF SYMPTOMATIC CAROTID DISEASE
Mr. Patrick Chong
Consultant Vascular & Endovascular Surgeon
Surrey Heart, Stroke and Vascular Centre
Frimley Health NHS Foundation Trust
Guildford
November 2014
Stroke – the figures
3rd leading cause of death
and
120 000 new strokes annually
500 000 new strokes annually
3 times as many women die from stroke as
from breast cancer.
Stroke – the costs
$51 billion - Stroke related treatment costs and
disability payments in 2003
£7 billion – Stroke related treatment costs and
disability payments in 2005
Treatment and research under funded in the UK?
£2 million per annum in the UK
c.f. Cancer £120 million and Heart Disease £43 million
Rothwell 2001 Lancet
The dangers of stroke
1 in 4 men before 85 years old
1 in 5 women before 85 years old
30% of stroke patients die within 30 days
Up to 32% will have a recurrent stroke within 30
days
1 in 4 stroke patients have a recurrent stroke
Brain Attack!
Vladimir C. Hachinski MD
Canadian Neurologist
r-TPA currently the only FDA approved
treatment for acute stroke to be given
within 4.5 HOURS of the start of symptoms.
The majority of patients don't report to the emergency room
until more than 24 hours after the onset of stroke symptoms
52 % of acute stroke patients unaware they were
experiencing a stroke.
Current organisation of care in UK
National Sentinel Audit
65%
2006
91%
18%
78%
2010
83%
50%
98%
Rapid transfer protocols
4%
High risk patients seen < 7 days
TIA clinic median waiting (days) 14
12%
35%
12
22%
43%
3
1 FPH
Stroke units
Thrombolysis offered
Neurovascular clinics
2004
71%
Current emergency care in UK
National Sentinel Audit
2006 vs. 2010 vs. 2014
Access to brain imaging < 12 hours 48% vs.
Access to brain imaging < 24 hours 95% vs.
87%
99%
Thrombolysis offered to eligible pts 18% vs. 50% vs. 80%
WHAT HAS CHANGED?
Stroke Telemedicine
Ambulance Services Pre-alerts
24 imaging and reporting for CT / CT in ED
ED led thrombolysis
“There is more to stroke
prevention than CEA” – AR
2007
Naylor
Risk factors for stroke
Modifiable
 Hypertension
 Smoking
 Hyperlipidaemia
 High grade carotid stenosis
 Atrial Fibrillation
 Diabetes
 Controversial e.g. OCP, Obesity, Alcohol
Non-modifiable
 Age
 Male sex
 Ethnicity
Fate of symptomatic carotid disease
Stroke incidence
1 Year
5 years
12-13%
5-9%
30-35%
25-45%
Previous Symptoms
TIA
Stroke
Norris JW et al. Stroke 1991
Fate of asymptomatic carotid disease
1 Year
< 75% ICA stenosis
1.5% Stroke
> 75% ICA stenosis
3.3% Stroke
7.5% TIA
Norris JW et al. Stroke 1991
Does plaque morphology matter?
Risk of stroke in symptomatic patients
95% stenosis
Non-ulcerated plaque
21%
95% stenosis
Ulcerated plaque
73%
NASCET study 1991
Does symptomatic
carotid stenosis matter?
Which patients should be treated first?
4799 patients tested using ABCD (2) score
2-day risk of stroke
Score of 0 – 3 (1012 patients)
Score of 4 – 5 (2169 patients)
Score of 6 – 7 (1628 patients)
1%
4.1%
8.1%
Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al.
Validation and refinement of scores to predict very early
stroke risk after transient ischaemic attack.
Lancet 2007
Carotid Endarterectomy (CEA)
The earliest report
Loucks et al. 1936
Union Medical College, Beijing, China.
Young male with recurrent TIAs
Right hemiplegia and aphasia
Excision of ICA occlusion
Patient recovered
Archives of Surgery 1938
Speed is of the essence!
Reconstruction of internal carotid artery in
a patient with intermittent attacks of hemiplegia
Eastcott, Pickering and Rob Lancet 1954
First carotid endarterectomy
1953
De Bakey JAMA 1975
The evolution of carotid
surgery
Reported 1955
Reported 1954
Reported 1975
Pre-CEA imaging – current UK







Duplex only
Duplex and MRA
Duplex and arch angiogram
Duplex and CTA
MRA only
CTA only
Arch angiogram only
GALA trial preliminary data
Gough et al. 2007
Leeds
65%
13%
9%
6%
2%
2%
2%
Mofidi et al. 2006
To patch or not to patch?
GALA Trial (current UK practice)
Always
Selective
Never
75%
20%
5%
“Patch angioplasty versus
primary closure for CEA”
Bond et al. 2003
Cochrane Database of Systematic Reviews
Outcome no different for different patch types
Significant reductions
Stroke
Death
Early Thrombosis
Late Restenosis
Intra-operative cerebral perfusion
Never shunt 5%
Speed
Shunt all patients 70%
Mainly GA patients
Selectively shunt 25%
Stump pressures 25%
EEG 5%
TCD 35%
Awake patient – regional cervical block
“Routine or selective carotid artery shunting for CEA”
Bond et al. 2001
Cochrane Database of Systematic Reviews
No evidence to support a policy of routine, selective or no shunting
How does surgery compare with best
medical therapy in symptomatic carotid
disease?
Primary
Endpoint
Trial
N
Stenosis
(%)
Medical
(%)
Surgical
(%)
P
value
ARR
(%)
NNT
NASCET
1991
659
>70
32.3
15.8
<0.001
11.3
9
ECST
1991
3008
>70
21.9
12.3
<0.001
1.5
68
VASST
1991
189
>50
19.4
7.7
0.01
17.2
6
Surgery versus Stenting outcomes
CAVATAS
2001
LEXINGTON 1
2001
SAPPHIRE
2004
EVA-3S
2006
SPACE
2006
ICSS
2010
CREST
2010
CEA / CAS
CEA / CAS
CEA / CAS
71%
No
Symptoms
CEA / CAS
CEA / CAS
CEA / CAS
CEA / CAS
Number
randomised
253 / 251
53 / 51
151 / 156
262 / 265
595 / 605
855 / 858
1251 / 1271
Cranial
nerve
8.7% / 0%
8.0 % / NS
5.3% / 0%
7.7% / 1.1%
NS / NS
5.3% / 0.1%
4.7% / 0.3%
Wound
6.7%/ 1.2 %
8.0% / 0 %
10.6% /
8.3%
1.2% / 3.1%
NS / NS
5.8% / 3.6%
0.2% / 1.6%
Stroke
9.9% / 10%
0% / 0%
20 % / 12%
/ 9.6%
7.4 % / 6.8%
4.1% / 7.5%
2.3 %/ 4.1%
Death
2%/3%
1.9% / 0 %
Combined
6%
1.2% / 0.8%
0.9% / 0.7%
0.8% / 2.2%
0.3% / 0.7%
Combined
Death
Any Stroke
5.9% / 6.4%
1.9% / 0%
6.1 % / 5.8%
For AS
patients
3.9% / 9.6%
6.5% / 7.7%
5.2% / 8.5%
3.2% / 6.0%
What would you rather choose?
Are you sure you
still want a stent?
Carotid endarterectomy outcomes
N=159
2007-2010
2007 J Vas Surg
*N=5513
2008
30-day Stroke /
TIA (%)
3.1% (n=5)
1.4%
1.8%
30-day MI (%)
2.5% (n=4)
0.5%
0.8%
30-day Death (%)
3.1% (n=5)
0.6%
0.5%
Cranial Nerve
Injuries (%)
2.1% (n=2)
0.4%
4.5%
Return to theatres
0.6% (n=1)
NS
2.1%
3
4.3
3
Median length of
stay (days)
Asymptomatic patients
8.8% FPH
*N=2236
64% MGH
16% NVD
Vascular Services Quality Improvement Programme (VSQIP)
November 2014
Surgeon outcomes for carotid endarterectomy
Dates 1st October 2010 to 30th September 2013
Institution
FPH
National
No. of
Procedures
211
Patients
Discharged
Without stroke /
death in 30 days
Adjusted
rate of
stroke /
death %
207
2.0
2.5
Days from
Length of
symptom to stay (days)
surgery
Median (IQR)
Median
(IQR)
8 (5,12)
12
2 (1,5)
Rationale for delaying CEA
Risks of haemorrhagic transformation infarct
with early surgery in acute stroke
Delay of 4-6 weeks recommended
Wylie (1964)
Thompson (1970)
DeWeese (1971)
Torgovnick (2007)
When should surgery be offered?
Risk of stroke and
timing of carotid endarterectomy
DOES TIMING OF SURGERY MATTER?
Carotid Endarterectomy Trialists Collaboration (CETC)
Number of ipsilateral strokes prevented at five years by performing 1000 CEAs in symptomatic
patients with 50-99% stenoses relative to days from last symptom to surgery
(based on reanalysis of CETC data)
Rothwell Lancet 2004
Faster surgery
for females
“Benefit from CEA in women was
apparent in those randomized within
2 weeks of their last symptomatic
ischemic event”
“Current guidelines in
Europe and the USA which state
only that CEA should be performed
within 6 months of last symptoms
should be amended in the light of
these results.”
Rothwell PM et al. Stroke 2004; 35: 2855-2861.
Delays! Delays! Delays!
Median time to surgery
Days
UK national carotid audit 1997
Newcastle audit 1995
Oxford audit 2005
GALA trial 2008
Frimley Park Hospital 2007-08
Frimley Park Hospital 2010-2014
189
120
100
82
67
8
University of Calgary experience Stroke 2006
 12% admitted patients required surgery
 72% operated within 2 weeks in 2002
 92% operated within 2 weeks in 2004
 37% operated within 2 weeks on NVD
 14% operated within 2 weeks at Frimley in 2010
 100% operated within 2 weeks at Frimley in 2014
 43 consecutive patients 12 months prior to NICE stroke
guidelines (July 2008)
 All TIA or non-disabling stroke





94% patients scored ABCD2 > 4 (high risk)
Mean time to consultant vascular opinion 28 days
81% patients had carotid duplex within 7 days
32% of high risk patients had CT scan within 24 hours
14% of patients had surgery within 2 weeks
ASIT Conference Nottingham March 2009
Conclusions (in 2008)
 WE WERE NOT FAST ENOUGH!
 Significant delays existed in our local urgent
carotid surgery pathway prior to the NICE
guidelines (July 2008).
According to NICE
How quickly do we
need to investigate &
Treat symptomatic
Carotid Stenosis?
7 days
South East Coast
Stroke Clinical
Reference
Group target for CEA
48hrs from
diagnosis
Stroke and TIA Surgical Helpline – allow direct consultant to consultant
referrals from HASU and acute stroke unites from RSCH, BNHH and HWPH
SEND IMAGES VIA IEP and FAX PATIENT DETAILS
GPs to refer to their nearest HASU or Acute
Stroke units or Rapid Access TIA clinic - MDT
Limitations of CEA








Severe OA / ankylosis cervical spine
Long length lesions
High bifurcations (above C2)
Previous cervical surgery
Previous cervical irradiation
Concomitant intra-cranial lesion
Concomitant thoracic lesion
Medically “high risk” patient
The first report of endoluminal
carotid intervention
“Catheter dilatation of proximal carotid
stenosis during distal bifurcation
endarterectomy.”
Kerber CW et al. 1980
Am J Neuroradiol
Carotid artery stenting (CAS)
Patient preparation
Femoral access
Aortic arch angiogram
Selective arch vessel cannulation
Intracranial and extracranial cannulation
Common carotid sheath access
EPD placement
Predilatation, stenting and postdilatation
Completion angiogram
EPD removal
Access site management
Postprocedural care and followup
Overview of CAS
Catch of the day!
Risk of micro-emboli: CAS vs. CEA

Diffusion-weighted MRI

Events in the 48 hours following CEA and CAS.
 19 / 27 (70%) CAS vs. 0 / 19 (0%) CEA

9 ipsilateral / 7 bilateral / 3 contralateral

3 CAS patients had post-operative neurology but all resolved within 36 hours.

The only factor associated with the development of microemboli was the use of a
diagnostic arch angiogram.

Preoperative MRI/A or CT-A recommended as alternative instead
NICE guidance for CAS
Safe and efficacious in the short term
Unsure about benefits in asymptomatic
Clear written information with consent
Audit and review all cases
Submit cases to registries and studies
Last updated September 2006
Asymptomatic carotid disease
- what was known before ACST
ACAS (USA) 1995
If a patient had a CEA before developing symptoms, they might be less likely to
have a stroke, providing the operation had a very low morbidity and mortality
Benefits confined to men under 65 years
No difference in outcome for stenosis 60-99%
Benefits were not greater for those with tighter stenosis as seen in the
symptomatic trials
MAJORITY OF PATIENTS IN USA & EUROPEAN SERIES ARE ASYMPTOMATIC!
ACST (UK) 2003
1560 allocated immediate CEA
1560 allocated follow-up with deferred CEA
3.4 years mean follow-up
Asymptomatic Carotid Studies
Total 5 year Stroke related mortality
What we know post ACST
 Benefits significant for men as well as for women up to
the age of 75 years.
 Benefits seen in patients with a stenosis > 70% on
ultrasound.
 5 year net risk of all strokes in ACST.
6% with immediate CEA
12% with deferred CEA
 Fatal and disabling stroke, not just stroke overall was
prevented by surgery.
ACST Caveats
 Best medical therapy (BMT) not optimised.
 Higher event rates compared with medical trials.
 Surgeons with event rates > 3%?
 CAPRIE (n= 19185)
 2 yr Stroke, MI, Vascular Death
 5.8% ASA vs. 5.3% Plavix
 4S study (n=4444)
Simvastatin 2.7% vs. Placebo 4.3%
 No plaque morphology characterisation.
RCTs of CEA for asymptomatic disease
Primary
Endpoint
Trial
N
Stenosis
(%)
Medical
(%)
Surgical
(%)
P
value
ARR
(%)
NNT
VA
1993
444
>50
20.6
8
<0.001
3
32
ACAS
1995
1662
>60
11
5.1
0.004
1.2
85
CASANOVA
2001
410
50-90
NS
NS
NS
NS
NS
ACST
2004
3120
>60
11.8
6.4
<0.001
1.1
93
Future asymptomatic data
 ECST-2
 Role of BMT + Surgery vs. BMT
 FPH will be recruiting Dr. Giosue Gulli PI
 ACST -2
 Role of CEA vs. CAS.
 Funding approved.
 Now recruiting.
 TACIT
 Role of BMT vs. BMT + CEA vs. BMT + CAS
Timing of surgery and efficacy
 Risks of further stroke are the highest in the first 2 weeks
following TIA/Minor stroke
 Early carotid surgery is safe in ASA I / II patients following
stable, non-disabling stroke
 Safer to delay ASA III / IV patients
 Patients with large areas of brain injury on CT or MRI
 Patients with unstable symptoms are at higher risk of
peri-operative stroke
Future role for
Best medical therapy?
Antiplatelets
NOACs
Statins
Antihypertensives
Can we go faster?
RACE (Rapid
Access Carotid
Endarterectomy)
 Follow the local Stroke/TIA pathways
 Refer to TIA clinic or ED
 Stroke units to admit high risk ABCD2 > 4 patients
 Fast track investigations for TIA/Stroke
 Surgical referral to vascular surgeon – USE HOTLINE
 Inform colleagues in primary and secondary care
Summary
The use of a stroke/TIA pathway to expedite access to assessment
Imaging and treatment is mandatory.
Carotid endarterectomy remains the “gold standard” in intervention
for symptomatic carotid disease.
The ideal patient group for CAS remains to be defined and long term
results from ICSS and CREST are awaited. The traditional indications
for CAS still hold. CAS patients should be entered into registries.
There is no place for the routine screening of patients for
asymptomatic carotid disease.