State of Art of Carotid Stenosi

XXVI WORLD CONGRESS OF
THE INTERNATIONAL UNION
OF ANGIOLOGY
July 1-5, 2012
Prague, Czech Republik
STATE OF THE ART IN
CAROTID ARTERY STENOSIS
G. Marcucci
Vascular and Endovascular Surgical Unit, S. Paolo Hospital
ASL RMF Civitavecchia-Rome (Italy)
G. Marcucci
Fundings/conflicts of interest
None
Apoplexy is, as I take it, a kind of
lethargy … a kind of sleeping in the
blood.
Henry IV.
William Shakespeare. 1598
•
William Harvey “de motu cordis” 1628.
Anatomo-physiology – Circulation of the Blood
•
Thomas Willis “de coerebri anatome” 1664.
Anatomo-physiology between cerebral afferent vessels
•
Abercrombie 1828.
Stroke not only due to intracranial vessels thrombosis,
but also to lost of blood pressure secondary to carotid
stenosis
•
Hans Chiari 1905.
Relationship between thrombus, carotid plaque and
embolization
•
John Ramsey Hunt 1913.
1.
CAUSAL RELATIONSHIP BETWEEN STROKE AND
INTERNAL CAROTID OCCLUSION.
2.
TIA AS COEREBRI CLAUDICATIO  NEED OF STUDY
OF VESSELS THAT REACH BRAIN
•
Egas Monitz 1927.
CAROTID AND CEREBRAL CIRCULATION ANGIOGRAPHY
BY DIRECT ARTERIAL PUNCTURE
Division of Vascular and Endovascular Surgery – “San Martino University Hospital - Genoa
University of Genoa – Italy
The relationship
between
carotid lesion
and
cerebral/ocular
neurological
symptoms.
• Miller-Fisher, from 1951.
1. Carotid steno-obstruction – main cause
of EMBOLIC STROKE
2. TIA secondary to carotid disease
premonitory of STROKE
3. Embolic or hemodinamic genesis of TIA
secondary to carotid stenosis
4. CMT tia manifestations are based on
carotid disease, as cerebral deficit,
both focal and emispherical
..intuition
that …one day surgeons
may even devise methods to
remove the offending plaque
The first successful reconstruction
of
the
carotid
artery
was
performed by Carrea, Molins, and
Murphy in Buenos Aires in 1951
Eastcott, Pickering and Robb
1953
Need of Study of
Carotid Surgery for Stroke
Prevention
Hemodinamical
problems
Thromboembolic events
Tissue causes
Carotid Disease
Cerebral
Ischemic Event
Need
of
Needof
of Study
Study of
“High risk Carotid
Carotid Plaque”
“High-Risk
Plaque”
Not only Degree of Stenosis, but also Carotid
Plaque Type and Morphology
Based on an accurate
Risk-Benefit Balance
Risk connected
Risk connected
to the Natural History
to the Disease Treatment
Trials in Symptomatic and
Asymptomatic patients
pubblished over
the years 1986-2004
North American Symptomatic
Carotid Endarterectomy Trial
NASCET
N Engl J Med 1991;325:445–53.
European Carotid Surgery Trial
ECST
Lancet 1998;351:1379–87
The Asymptomatic Carotid Surgery
Trial
ACST
Lancet 2004;363:1491–502
 Benefit and Safety of
SYMPTOMATIC patients,
morbidity and mortality
CEA in
with low
 There is now level 1 evidence verifying
the benefit of CEA over medical
therapy in ASYMPTOMATIC patients
with flow-reducing carotid stenosis and
truly anatomic high risk scenario
Percutaneous transluminal angioplasty in
arteriosclerotic internal carotid artery
stenosis.
Bockenheimer SA, Mathias K. AJNR Am J Neuroradiol. 1980
Percutaneous angioplasty of atherosclerotic
and postsurgical stenosis of carotid arteries.
Theron J, Raymond J, Casasco A, Courtheoux F.
AJNR. Am J Neuroradiol. 1987
New triple coaxial catheter system for
carotid angioplasty with cerebral protection
Theron J, Courtheoux P, Alachkar F, Bouvard G, Maiza D
AJNR Am J Neuroradiol. 1990
.
GREAT DEBATE
CAS
could be not inferior
…?
or superior
CEA
Prospective randomized
Studies
Interrupted Trials
LEICESTER TRIAL:
71% Neurological complications in CAS
J Vasc Surg 1998;28:326-34.
WALLSTENT TRIAL:
12.1% Neurological complications in
CAS
Stroke 2001; 32: 325.
Cerebral protection device not used
EVA-3S Trial:
27% Neurological complications in CAS group
without protection
9% Neurological complications in CAS group with
protection
15% global neurological complications
Stroke 2004; 35.
Prospective randomized
Studies
No interrupted Trials
CAVATAS
Fundamental flaws included the fact:
 the actual treatment to which the patients were randomized was often
delayed in being carried out such that many of the events gathered in an
intention to treat analysis were not related to the intervention itself
 the endovascular technique used in this study were primitive compared
to contemporary practice
 no embolic device available (only 26% with embolic protection)
 only 30% stents were used
Major flaw was the excessive morbidity of both
treatments (10% mortality at 30 days in both treatment groups)
This trial can be considered of historical interest only
SAPPHIRE
BIASED
Cas was supported as “not inferior” to carotid
endarterectomy in “high risk” patiens
Asymptomatic carotid stenosis: CEA vs CAS
( n. 334 )
20,0%
15,0%
10,0%
5,0%
0,0%
stroke/MI/death
cranial nerve palsy
CEA
CAS
10,20%
4,90%
5,40%
0%
P=0.20
The SAPPHIRE Trial, N Engl J Med 2004
2004
Richard P. Cambria, M.D.
N Engl J Med 2004; 351:1565-1567
 disproportionate number of patients were considered unacceptable for
randomization, raising considerable doubt about the surgical sophistication at
the study centers - 60% of the patients enrolled were considered too high
risk for CEA
 The only difference in the two study groups was provided by the inclusion
of non-Q wave myocardial infarction as endpoint , which seems ephimeral
when considered in the real context of contemporary carotid surgery
 Operators too inexperienced.
 The principle investigator had a major conflict of interest. He received
royalty income on the distal protection devices used in the study. Dr. Yadav was
subsequently fired from the Cleveland Clinic in 2006 for improperly
disclosing conflicts of interest.
ASCT, EVA-3S, SPACE or multitude of surgical series detailed anything
similar to SAPPHIRE reported rates of MI after CEA
 Too high rates of postoperative complications and cross-over CAS to CEA
 The very controversial point is what the definition high risk should
constitute 30% of the patients were considered “high risk” because there
was a redo carotid intervention
EVA-3S and SPACE
 Indicate either a 2.2 fold increase in 30 day stroke/death
for CAS vs CEA in symptomatic patients or inability to prove
CAS is not inferior to CEA in symptomatic patients
 the authors of EVA3S indicate that even after substration of
the patients treated without embolic protection, the
difference between CEA vs CAS was still significant, further
more there was no difference in stroke risk across their CAS
center as a function of case numbers.
CAPTURE /EXACT PM
 30 day stroke/death rate in symptomatic
patients was nearly 12% with CAS
 have indicated that recently(<14days)
symptomatic patients have a horrific (nearly
16%) risk of stroke/death with CAS
CAPTURE 2
2010
Patients > 80 years old have
higher
periprocedural
event
rates than no octogenarians.
Age, symptomatic status, and lesion
length should be considered when
identifying
appropriate
for the procedure.
candidates
Administrative Database
Studies

CAS
was
accompanied
by
a
stroke/death rates-compared to
two-fold
increased
in
CEA.
 The data were even more disparate when symptomatic
patients were considered
SVS Vascular Registry
2009
indicates that composite death/stroke/MI rate
is significantly higher after CAS vs CEA (6.4%
VS 2.6% P<.0001) in risk adjusted data
indicates significantly higher rates of 30day
stroke/death for CAS vs CEA in symptomatic
patients (4.6% vs 1.97% p=?.003)
ICSS
European Stroke Conference
ICSS
ICSS
ICSS
ICSS
ICSS
The Lancet - Correspondence
1
2
The Lancet - Correspondence
1
EVA –3S; SPACE; ICSS
2
Interventionalists’
Experience
30-day risk
of stroke or
death
More than 50
procedures
12·2%,
Equal or Fewer than
50 procedures
11%
were being
proctored
7.1%
In certain situations –
CAS likely will be the treatment
of choice of recurrent stenosis after CEA
2010
2012
Abbott AL, Adelman MA, Alexandrov AV, Barnett C C HJ, Beard J, Bell P, Björck M, Blacker D, Buckley CJ, Cambria RP,
Comerota AJ, Connolly ES Jr, Davies AH, Eckstein HH, Faruqi R, Fraedrich G, Gloviczki P, Hankey GJ, Harbaugh RE, Heldenberg
E, Kittner SJ, Kleinig TJ, Mikhailidis DP, Moore WS, Naylor R, Nicolaides A, Paraskevas KI, Pelz DM, Prichard JW, Purdie G,
Ricco JB, Riles T, Rothwell P, Sandercock P, Sillesen H, Spence JD, Spinelli F, Tan A, Thapar A, Veith FJ, Zhou W.
CEA STUDIES
Admirable Results of CEA in
contemporary practice
2009
In major series periprocedural stroke/death
occured in less than 2% and was not increased in
octogenarians
 1% year risk of significant recurrent stenosis
Asymptomatic carotid stenosis: CEA vs CAS
( n.1,411 )
8,0%
6,0%
4,0%
2,0%
0,0%
stroke/MI/death
CEA
CAS
1,97%
4,60%
P=0.003
2009
Sidawy AN, The Society of Vascular Surgery Registry, 56 Centres
CEA STUDIES
Admirable Results of CEA due to new
2008
process of perioperative care (fast track
protocol, beta blockers, antiplatelet agents and
more recently statins)
CEA STUDIES
Admirable Results of CEA due to more
adequate choice of the surgical technique
2000
The comparisons of eversion versus primary closure and patch versus
primary closure revealed a statistical significant difference (with logrank test, P = .0002 and P = .0008, respectively
CEA STUDIES
Admirable Results of CEA due to more
adequate choice of the surgical technique
2007
• Primary closure during CEA should be abandoned in favor of either standard
endarterectomy with patch angioplasty or eversion endarterectomy.
• Carotid patch angioplasty decreases the risk for perioperative death or stroke and longterm risk for ipsilateral ischemic stroke.
Our experience
January 2005 - December 2010
Characteristics of patients
625 CEA in 545 patients
No. patients/procedures
Age
Male
Female
Asymptomatic
Symptomatic
Smoking
Hypertension
Diabetes
Hyperlipidemia
383 (61.2%)
242 (38.7%)
Overall Normal risk
n/%
545/625
372/437
High-risk
n/%
173/188
P
-
75 ± 7.2
78±4,1
74± 8.2
NS
383/61.2% 265/60.6% 118/62.7% NS
242/38.7% 171/39.1% 71/37.7% NS
280/44.8% 217/49.6% 63/33.5% .004
345/55.2 % 220/50.3% 125/66.4% .004
196/31.3% 122/27.9% 74/39.3% NS
452/72.3% 307/70.2% 145/77.1% NS
126/20.1%
88/20.1% 38/20.2% NS
343/54.8% 196/44.8% 147/78.1% .002
Our experience
January 2005 - December 2010
neurological
symptoms
Symp.
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Symp.
302
(55.4%)
1
Asymp
.
Asymp
.
243
(44.6%)
2
Our experience
January 2005 - December 2010
Gender
Our experience
January 2005 - December 2010
Our experience
January 2005 - December 2010
Patients data and comorbidities
54 (10.1%)
Surgical procedure (1)
Surgical data
Patch 541 (86.3%)
By-pass 5 (0.7%)
Eversion 84 (13.4%)

Direct suture 3 (0.5%)
Surgical procedure (2)
 Duplex
scan detection
 MiniSkin Incision (5-7 cm)
 No carotid bulb mobilization
 Preventive ICA clampage
2011
Our experience
January 2005 - December 2010
Complications
4
3
0.48%
0.48%
3
2
2
0.16%
1
1
0
death
major stroke
minor stroke
Our experience
January 2005 - December 2010
Complications
Current and future Considerations
2009
…”Important reason underlying uncertainty about how best to manage
patients with asymptomatic carotid disease is a growing belief that
in what now constitutes
’ may have
to levels below that observed
in ACAS and ACST. This is a very important issue to be resolved as if the
annual rate of fatal/major stroke falls below 1.1%, no benefit will ever
accrue to any patient from CEA”….
Effects of intensive medical therapy
in asymptomatic carotid stenosis
(n.468)
20%
16%
12%
8%
4%
0%
stroke/death/MI or
CEA
< 2003
> 2003
17,60%
5,60%
P <.001
Spence JD, Arch Neurol 2010
Revascularisation for carotid stenosis
100%
80%
60%
40%
20%
0%
asymptomatic %
USA
UK
Italy
92,0%
20,0%
70,6%
McPhee JT, J Vasc Surg 2008
2008 Great Britain and Ireland Carotid Endarterectomy Audit
2008 Italian Vascular Registry
Current and future Considerations
Evidence supporting a declining stroke risk with time
Current and future Considerations
2009
... “In our opinion,consensus to how best to manage
patients with asymptomatic carotid stenosis will only
be achieved if one of the trials evaluating CEA with
CAS in asymptomatic patients includes an
adequately powered third limb for medically
treated patients
…and analysis of type carotid plaque”…
Current and future Considerations
Future Trials
Future Trials
SPACE 2
Clinical Trial Protocos
• The control groups in the large trials for asymptomatic carotid artery disease (ACAS and ACST)
originate from more than a decade ago and, for the most part, have not received a medical primary
prevention strategy that would now be considered the standard according to current national and
international guidelines.
• For this reason, a three-arm trial (SPACE2; ) with a hierarchical design and a
recruitment target of 3640 patients is chosen.
• Firstly, a superior trial of intervention (carotid artery stenting or carotid
endarterectomy) vs. state-of-the-art conservative treatment is designed.
• In case of superiority of the interventions, a noninferiority end-point will be tested
between carotid artery stenting and carotid endarterectomy.
Future Trials
TACIT
Clinical Trial Protocos
• Primary study aim: Can optimized medical therapy, with or without revascularization by
carotid endarterectomy or stenting, reduce the risk perioperative mortality and 5 year all
strokes and neurological decline (5-yr primary end-point)?
• Study design: TACIT is a prosective collaborative U.S. and EU unblinded, three arm,
randomized trial comparing three treatment strategies in patients with duplex evidence of >
60% carotid stenosis:
• 1 otimal medical therapy alone;
• 2 medical therapy with carotid artery stenting (CAST)
• 3 medical therapy with carotid endarterectomy
• There will be strict monitoring of medical compliance and cardiovascular risk factors. All
patients will have quality of life and cost effectiveness data collected
• TACIT plans to evaluate neurocognitive changes, quality of life issues and carotid
plaque characteristics
GUIDELINES
for the invasive treatment
of Carotid Disease
based on existing
published evidence and
not on individual
preferences or practice
Division of Vascular and Endovascular Surgery
“San Martino” University Hospital – University of Genoa
BASED ON:

Neurological Symptomatology
Degree of carotid stenosis



Medical co-morbidities
Vascular and local anatomical
features

Morphology of carotid stenosis

Team complication rates
Symptomatic Carotid Stenosis
Symptomatic Carotid Stenosis
Symptomatic Carotid Stenosis
Clinical/pathological factors to optimize referral of symptomatic carotid
stenosis > 70% to CEA in addiction to extent of carotid narrowing
- Age
- Gender
- Ischemic
complications
- Rothwell risk-
factor scores
Symptomatic Carotid Stenosis
Clinical/pathological factors to optimize referral of symptomatic carotid
stenosis > 70% to CEA in addiction to extent of carotid narrowing
- Delay-to
surgery from
the first
presenting
event
Lancet. 2004
Symptomatic Carotid Stenosis
Clinical/pathological factors to optimize referral of symptomatic carotid
stenosis > 70% to CEA in addiction to extent of carotid narrowing
Timing
Asymptomatic Carotid stenosis
Asymptomatic Carotid stenosis
 Type of plaque from 1(soft) to 5 (hard)
94% serious events occured in patients with palque 1-3
 Degree of stenosis (RR 1.6)
 Hystory of controlateral TIA (RR 3.0)
 Creatinemia(RR 2.1)
1995
Presence of these three risk factors characterized the subgroup with the
highest risk of an ischemic cerebral event
(annual event rate 7.3%; yearly stroke rate 4.3%)
Duplex Scan Plaque Morphology
Stenosis ~ 60%
Embolic risk
Fibrotic
Calcific
Lipidic
Haemorragic
Ulcer.
Carotid Angioplasty/Stenting
Division of Vascular and Endovascular Surgery
“San Martino” University Hospital – University of Genoa
Carotid Angioplasty/Stenting
INDICATIONS
Carotid Angioplasty/Stenting
INDICATIONS
 Restenosis
 Previous neck dissection)
 Previous neck radiotherapy
 Previous tracheostomy
 Rigid or hostile neck
High bifurcation
Controlateral laryngeal nerve palsy
 IntraCranial extension ICA
 Clavicular extension CCA
Carotid Angioplasty/Stenting
CONTROINDICATIONS
Plaque with irregular
surface
Pre-occlusive Stenosis
Tortuosity
High Embolic Risk
Calcific Stenosis
• Stretched Aortic Arch
• Common Carotid Acute
angle origin
• Common carotid kinking
•Thromboembolic material
• Soft Stenosis
• Post-procedural embolization
Carotid Angioplasty/Stenting
-
Recommendation Grade A:
Since the current evidence is still insufficient for quality and quantity, endarterectomy
should not be replaced with endovascular procedures for elective surgical correction of
carotid stenosis
-
Recommendation Grade C:
Carotid stenting, if performed with adequate procedural quality levels, should be used
instead of endarterectomy in presence of severe vascular or cardiac comorbidities
-
Recommendation Grade C:
Carotid stenting, if performed with adequate procedural quality levels, should be used
instead of endarterectomy in selected cases: restenosis after endarterectomy, cranially
extendings stenosis, post irradiation stenosis
-
Recommendation Grade D:
Carotid stenting should not be performed when the presence of endoluminal thrombotic or
thromboembolic material is suspected, on in presence of tortuous supra-aortic vessels
-
Recommendation Grade C:
Carotid stenting should not be performed, unless adequate crebral protectioon devices are
of Vascular and Endovascular
Surgery – “San
Martino University
Hospital - Genoa
applied, on whichDivision
the interventionist
is familiar,
trained
and expert
University of Genoa – Italy
2010
When the choice of
treament is not clear …
When the choice of
treament is not clear …
Considerations
• Progressive improvement of medical therapy (antiplatelets,
statins,…) has to be taken in account
• Current imaging techniques are useful to identify
vulnerable plaques and may improve the selection criteria
for CEA or CAS, no more based only on degree of stenosis
• Early and current RCTs have several limitations, and
registry data and population-based studies show outcome
rates very different
• CEA remains the “gold standard” also in asymptomatic
patients.
• The Vascular Surgeon is the only «figure» able to choose
and perform the BMT, CEA and CAS.
Tank you for your attention