1. Carotid Stenosis
Known natural history despite best medical tx
Preventing stroke in Carotid Only surgical disease w/ proven tx (multiple RCT’s)
Stenosis: Stenting or Question: not whether to treat, but how to treat
Endarterectomy? symptomatic versus asymptomatic
high-risk versus low-risk
CEA versus CAS
Symptomatic RCT’s: Best Med Tx ± CEA
NASCET Pooled NASCET/ECST data (Stroke 2004;35:2855)
2,885 pts w/ TIA or minor stroke within 120 days
70-99%: 17% ARR (65% RRR) / 2 yrs Both studies demonstrate remarkably similar benefit of
50-69%: 6.5% ARR (29% RRR) / 5 yrs intervention
<50%: no benefit Risk of recurrent stroke in symptomatic stenosis is early →
ECST (reanalysis by NASCET criteria, Lancet 2003;34:514) treatment is NOT elective!
3,024 pts w/ TIA, retinal infarction, or non-disabling stroke Women lose most from delayed treatment
within 6 months
70-99%: 21.2% ARR / 5 yrs
50-69%: 5.7% ARR / 5 yrs
<50%: no benefit (harm if <30%)
Asymptomatic RCT’s: Best Med Tx ± CEA
ACAS (JAMA 1995;273:1421)
1,662 pts w/ angio or validated doppler > 60%
5.9% ARR (53% RRR) / 5 yrs
required low surgical M&M (1.5%)
no stat. sig. benefit for women
ACST (Lancet 2004;363:1491)
3120pts w/ doppler > 60% stenosis
5.4% ARR (11.8→6.4% risk) / 5 yrs
results more robust than ACAS
surgical M&M more realistic (3.0%)
50-69%
70-99%
Pooled NASCET, ECST subgroup analysis… Stroke 2004,35(12):2855
1

2. Pooled ACAS/ACST data (Cochrane review, June 2005)
proven benefit of CEA for asymptomatic stenosis in men
women, elderly benefit to a lesser degree
CEA for asymptomatic stenosis Cochrane Review, June 2, 2005
ARR for stroke or death: Symp. vs Asymp.
(<68, <75) NASCET/ECST symptomatic 70-99% ~ 8.5% per year
ACAS/ACST asymptomatic >60% ~ 1% per year
Caveats:
1. Symptomatic benefit is chiefly upfront: first several months
2. Asymptomatic benefit is long-term: ~ 2 yrs for curve crossover
Questions:
1. How does this CEA data relate to decision-making regarding
CAS (real world, high-risk pts, peri-op M&M + risk of MI…)?
2. Would decreased periprocedural M&M of CAS permit further
gains in risk reduction, across more subgroups??
CEA for asymptomatic stenosis Cochrane Review, June 2, 2005
High Risk Patients…excluded a priori High Risk Patients…found post hoc
ACAS Exclusions NASCET Exclusions
Previous stroke Age older than 79 years;
Previous CEA Previous ipsilateral endarterectomy;
Previous EC-IC bypass Intracranial stenosis more severe
than the surgically accessible
NASCET Surgical risks (30 day periop M&M):
High risk because of associated
lesion
medical illness
Lung, liver, or renal failure
Long-term anticoagulation therapy
Lack of angiographic depiction of both
Intolerance of aspirin or long-term carotid arteries and their symptomatic ≥ 70% 5.8% total = 3.7% minor
aspirin therapy at a high dose intracranial branches. stroke, 1.5% major stroke,
Life expectancy <5 years Uncontrolled hypertension or diabetes
Surgically inaccessible lesion Unstable angina pectoris 0.6% death
Myocardial infarction within the
previous 6 months
Contralateral carotid endarterectomy symptomatic ≥ 70% AND 14.3% total
within the previous 4 months
Progressive neurologic dysfunction contralateral occlusion
A major surgical procedure within the
previous 30 days.
2

3. Significant percentage of patients
NASCET / ACAS / ACST
with carotid stenosis are at high
surgical risk or have one or more
CEA reduces stroke risk in Selected exclusion criteria
Patients
Bottom Line Message…
Increasing data over the past
In low risk pts the risk of stroke and death
from CEA must be decade shows CAS is better
Less than 7% for symptomatic patients
Less than 3.5% for asymptomatic patients for these patients
Early randomized trials of CAS Embolic Events
The biggest problem with CAS
First randomized trial of CEA vs. CAS halted due
to high rate of complications in stented pts
Naylor et al. 1998
Despite advances in stent technology and
antithrombotic/antiplatelet regimens, significant
Embolic Stroke
complication rate in stent trials remained 7-10%
in late 1990’s
Lack of
Technology, Experience, Embolic Protection
When do most embolic events occur? Distal embolic protection devices
Angioplasty Plaque fracture
Debris release
Stent + Post Dilatation Plaque strainer
Debris release Cheese Grater
effect
In all CAS FDA studies with emboilc protection
Embolic Stroke visible debris was collected in over 50 % of cases
3

4. CAS With and Without Protection CAS
a systematic review Complications
Kastrup et al Stroke 2003 (N=1222)
Without With
Protection Protection
without DEP with DEP TIAs 8.1% 2.6
Minor Stroke 2.1% 1.3
Minor stroke 94/2537(3.7) 5/896(0.5) Major Stroke 1.1% 0.3
Major stroke 28/2537(1.1) 3/896(0.3) 30-day Mortality 0.5% 0
Death 8/2537(0.3) 8/896(0.8) Death & Stroke 3.8% 1.6
Any stroke or death 140/2537(5.5) 16/896(1.7)
Mathias & Schwarz
CAS: DWI and clinical outcome +/- DPD Embolic Protection
Kastrup et al, Stroke 2006;37:2312
Three Types
Filtration
Must completely fill the vessel and have a high capture efficiency
Maintenance of distal flow
Distal Occlusion with a balloon
Flow arrest must be tolerated/atraumatic
Particle washout/aspiration
Flow Reversal
Must tolerate hemodynamics of flow reversal
Challenges with second generation device need to be overcome
Concept ECA
ICA
Distal Protection Devices
Overview
Filter Occlusion Filter Devices
AccuNet (Guidant)
FilterWire (EPI-BSC)
NeuroShield/Cardio-
Shield (MedNova)
E.Trap (Metamorphics)
The Trap VFS
(MicroVena)
Sentinel (BSC/SciMed)
Spider
Distal Occlusion Devices
CCA PercuSurge (Medtronic)
Triactive Kensey Nash
Reversal
4

5. Distal Protection
Distal protection device placed to distal
straight segment
Available off the shelf
EPI Filterwire- Applicable to most
(>95%) of lesions
Accunet
Emboshield
Percusurge
Small ICA (<3mm)
Acute carotid occlusions - to
prevent embolization of large
column of clot that might
overwhelm a filter device
Study devices only
Spider – Most deliverable (for difficult
lesions) but filter has larger pores
Angioguard
MAE One Year Rate Trends in High Risk CAS Trials Carotid Revascularization Using
Endartectomy or Stenting Systems (CaRESS)
15.7%
16
Multicenter, prospective, non-randomized trial
14
comparing CAS (with DEP) and CEA
12
10.2%
Symptomatic > 50% Asymptomatic > 75%
10
9.1% Choice of CEA vs. CAS up to treating physician
8.3%
Primary endpoint
8
All-cause mortality at 30 days and 1 year
6 4.5% Secondary endpoints
4 Composite 30-day all-cause mortality or stroke:
residual stenosis, restenosis, repeat angiography,
2
and carotid revascularization at 30 days and 1 year;
0
CABERNET
CABERNET BEACH
BEACH ARCHeRI 1
ARCHeR ARCHeR2
ARCHeR 2 SAPPHIRE
SAPPHIRE* and quality of life changes at 1 year.
*Registry Arm Results
CaRESS Demographics CaRESS Primary Endpoints
Variable CEA (n=254) CAS (n=143) P value
Symptomatic 33% 31% NS Stent CEA P value
Previous CEA 11% 30% < 0.01 (N=143) (N=254)
Previous CAS 0% 6% < 0.01
Previous peripheral angioplasty 0.4% 2% NS
2.1% 3.6% NS
Death/CVA @ 30
Contralateral stenosis 40% 34% NS days
CAD or previous AMI 61% 66% NS Death/CVA @ 1 year 10.0% 13.6% NS
CHF 17% 13% NS
Death/CVA/MI @ 30 2.1% 4.4% NS
HTN 81% 81% NS
days
Hypercholesterolemia 70% 64% NS
Death/CVA/MI @ 1 10.9% 14.3% NS
Diabetes 24% 29% NS
year
Peripheral vascular disease 41% 45% NS
5

6. CaRESS Secondary Endpoints SAPPHIRE
Randomized trial of CAS with DEP compared with CEA in
a high-risk population
Endpoint CAS CEA P value Symptomatic stenosis of at least 50%
(N=143) (N=254)
Asymptomatic stenosis of at least 80%
Residual stenosis 0.9% 0.0% NS
747 enrolled: 334 underwent randomization
Restenosis 6.3% 3.6% NS
Repeat angiography 3.6% 2.1% NS Primary endpoints
Composite of death, stroke, myocardial infarction
Carotid revascularization 1.8% 1.0% NS
within 30 days, or
Death or ipsilateral stroke at 31 days and 1 year
SAPPHIRE: 3 Year Data
SAPPHIRE: initial results
Endpoint CAS CEA P value
(N=159) (N=151)
Death 7.0% 12.9% 0.08
All Stroke 5.8% 7.7% 0.52
Major ipsilateral stroke 0% 3.5% 0.02
Myocardial infarction 2.5% 8.1% 0.03
Cranial nerve palsy 0 5.3% 0.003
Target vessel 5.1% 7.5% 0.40
revascularization
MAE 12.0% 20.1% 0.05
Trends favor CAS
SAPPHIRE: 3 Year Data SAPPHIRE: 3 Year Data
6

7. SAPPHIRE: 3 Year Data SAPPHIRE: 3 Year Data
ARCHeR
Multicenter single arm trial evaluating CAS in high risk pts ARCHeR Results Update
Combined primary endpoint of death, stroke, MI @ 1yr
Guidant ACCUNETTM Filter OPC ie Historical
ARCHeR 1 8.3% Control For CEA
ARCHeR 2 10.2% = 14.5%
ARCHeR 3 9.6% (JVS 2006;44:258)
Event-free survival was
90.4% at 1 year and 88.4%
at both 2 and 3 years.
Target lesion revasc. was
2.2% and 2.9% @ 1 and 2
years respectively.
Low-risk Trials
Bottom line from recent data… Symptomatic: EVA-3S
- symptomatic stenosis ≥ 60%
ARCHeR - 30-day any stroke/death: 3.9% CEA, 9.6% CAS
- halted after 527 patients recruited
CaRESS - embolic protection not used initially, CAS operators relatively less experienced…
SAPPHIRE Symptomatic: SPACE
- symptomatic stenosis ≥ 70%
- 1183 patients randomized to CAS vs CEA
1. CAS M&M appears slightly better than CEA - 30-day ipsilateral stroke/death: 6.84% CAS, 6.34% CEA (ns)
- embolic protection used in only 27%
2. At 1 year, CAS is equally efficacious as CEA - failed to prove non-inferiority (halted, underpowered)
Asymptomatic: ACT I
- Randomization of CAS compared with CEA in low-risk patients
…in HIGH RISK patients…! - 3 CAS to 1 CEA randomization
- Ongoing
7

8. CREST
CREST: RPCT in Low Risk Pts Multicenter prospective randomized trial CAS vs. CEA
Results from the Lead-in Phase Guidant ACCUNETTM Filter
After ACST, eligibility in
CREST expanded to involve
asymptomatic pts > 60%
Plans to enroll 2500 pts
CREST CREST Lead Ins
Multicenter prospective randomized trial CAS vs. CEA
Symptomatics at 30 days
Periprocedural stroke in 4 of the 81 Lead-In patients treated without EPD (4.9%)
Periprocedural stroke in 12 of 332 with EPD (3.6%)*
No significant difference by symptomatic status, co-morbidities, or timing of stroke 30 day combined M&M compared to NASCET
* 1st generation Acunet was bulky and inflexable!!
Study Patients Stenosis Stroke &
Death
CREST Lead-In Patients
(AHA 2003) NASCET 328 >70% 5.8%
10.0%
eriprocedural
8.0%
4.9%
CREST 191 >50% 5.7%
troke
6.0% 3.6%
4.0%
S
2.0%
P
0.0%
Without With ACCUNET
ACCUNET N=81 N=332 ^As of October 24, 2004
CREST Lead Ins CREST
Asymptomatics at 30 days
Continues to enroll patients (>700)
30 day combined M&M compared to ACAS
CREST (lead-in) MAE
Study Patients Stenosis Stroke & Death 191 Symptomatic patients – 5.7%
395 Asymptomatic patients – 3.5%
ACAS 721 >60% 2.2%
Asymptomatic patients now included
CREST 395 >70% 3.5%
Await conclusion of enrollment and global statistica
^As of October 25, 2004
analysis
8

9. CREST Is the Best Designed RPCT
Conclusions
However CREST will take Years to complete 1. CEA remains gold standard, against which any new
CREST is enrolling NASCET/ACAS type pts treatment must prove safety & efficacy
not high risk patients 2. High-risk pts should be treated by CAS: proven
To meet the need for high risk pts and FDA efficacy with less risk
approval company sponsored registries have
3. Low-risk patients should undergo CEA OR be
been performed
enrolled in trials: CREST, CaRESS…
4. CAS and CEA can be complementary…the
compleat clinical must have every technical arrow in
his/her quiver
9