1. Symptomatic Patients: When, How, and Why to Intervene?
Kenneth Rosenfield, MD, FACC, FAHA
Section Head, Vascular Medicine and Intervention
Massachusetts General Hospital
Boston, Massachusetts, U.S.A.

2. Kenneth Rosenfield, MD Conflicts of Interest
Consultant
Abbott Vascular
Baxter
Harvard Clinical Research Institute
IDEV
Lutonix
Lumen
Micell
Complete Conference Management
VuMedi
Equity
Icon
CardioMEMs
Contego
Medical Simulation Corporation
Primacea
Research or Fellowship Support
Abbott Vascular
Cordis
Bard
Boston Scientific
Baxter
Atrium
Invatec-Medtronic
IDEV
Lutonix
Board Member
VIVA Physicians

3. Natural Hx: Annual Stroke Rates with Carotid Stenosis
Symptomatic
Asymptomatic ? ?
Hi-risk
Standard-
risk
Standard surgical risk patients
70-99% 13%
50-69% 4.4%
60-99% 2-2.5%
…BUT, MOVING TARGET…
A) Probably different now, given advances in medical therapy
B) Great variability based on lesion morphology/other factors

4. Therapy for for stroke prevention
RCT’s: CEA vs. OMT
Symptomatic
High-risk
Asymptomatic
High-risk
None
Symptomatic
Standard-risk
Asymptomatic
Standard-risk
NASCET
VA Trial
ECST

5. Does CAS prevent stroke in Sxatic pts …compared to surgery
Does CAS prevent stroke in Sxatic pts …compared to surgery? Requires head to head comparison(RCT)
In which subgroup:
Conventional or High-surgical risk?
<>80 y.o.? Male/female? Etc, etc, etc….
We need more data

6. What are the data available? RCT’s: CAS vs. CEA
completed*
SAPPHIRE *
ongoing
Symptomatic
High-risk
Asymptomatic
High-risk
None
None
Symptomatic
Standard-risk
Asymptomatic
Standard-risk
EVA3s, SPACE 1
ICSS*
ACT 1
CREST

7. Controversial: Are CAS and CEA Equivalent?
Stroke Prevention by Revascularization What evidence we DO have in sxatics…
RCT:
CEA vs. medical Rx in standard surgical risk patients (NASCET, ECST, VA Cooperative Trial)
CAS vs. CEA in high surgical risk patients (SAPPHIRE)
CAS vs. CEA in standard risk patients
(CREST, EVA3S, ICSS)
CEA wins!
Controversial: Are CAS and CEA Equivalent?

8. SAPPHIRE 3-Year Outcomes
Freedom from MAE
N Engl J Med 2008;358:1572-9

9. Composite for death and stroke XACT and Capture 2 - All high risk patients
Gray et al., Circ Cardiovasc Intervent 2009; March 6

10. Composite Death and Stroke Symptomatic patients <80 y.o.
NB: >80 y.o. patients had 10.5% composite
Gray et al., Circ Cardiovasc Intervent 2009; March 6

11. CAS for Stroke Prevention: Which high-surgical risk pts
CAS for Stroke Prevention: Which high-surgical risk pts? Current CAS Coverage

12. Qualifying high surgical risk conditions
Per CMS (3/05)
A. Anatomical Conditions
CCA lesion(s) below clavicle
High cervical Internal Carotid Artery (ICA)
Previous neck radiation
Prior neck surgery/radical neck dissection
Restenosis of prior CEA
Tracheostomy
Contralateral carotid occlusion
Contralateral laryngeal nerve palsy

13. Qualifying high surgical risk conditions
Per CMS (3/05)
B. Co-morbid Conditions
Clinically significant cardiac disease
Recent Myocardial Infarction (MI)
LVEF < 30%
CHF or NYHA Class III or IV
Abnormal stress test
Need for open-heart surgery
Unstable angina: CCS Class III/IV
• Severe pulmonary disease
Age >80
ESRD on dialysis

14. ICSS: Outcomes CAS (853) CEA (857) HR P value Death, stroke, MI 8.5%
5.2%
1.69
0.006
Any stroke
7.7%
4.1%
1.92
0.002
Any stroke or death
4.7%
1.95
0.001
Disabling stroke or death
4.0%
3.2%
1.28
0.34
All-cause death
2.3%
0.8%
2.76
0.017

15. The evolution of CAS in symptomatic patients: EVA-3S, SPACE, ICSS are outliers
AHA guideline limit

16. Design Flaws in European RCT’s
ICSS: 5 major strokes (30% total) from 2 inexperienced sites enrolled 11 CAS patients.
EVA-3S: 5% (1 in 20) of CAS pts “converted” to emergent CEA.
Roffi M, Sievert H, Gray WA, et al. Lancet Neurol 2010:9:

17. SPACE: Operator Volume Matters
Class I = 0.98 ((95% CI 0.50–1.94, p=0.95)
Class II = 1.13 (95% CI 0.47–2.77, p=0.77)
Class III =11.56 (95% CI 1.40–253.45, p=0.01)
CAS
P = .01
P = .77
P = .95
CEA
This slide shows that more experienced operators have fewer complications.
10 to 24
<10
≥25
Class I
Class II
Class III
Fiehler J, et al. Neuroradiology (2008) 50:

18. ICSS: further observations
Very low rate of MI in both groups suggests that they weren’t routinely assessed (unclear from Methods)
Embolic protection not mandated
Only documented in 72% of cases
Major stroke was ~2% in each group, double what is seen in US
Poorly trained operators getting poor results

19. Which pts for CAS ? It’s mostly about case selection…
Restenosis
Smooth, non-ulcerated, focal
Heavy Concentric Calcification
Extensive Ulceration
String sign (distinguish from underperfusion)
Thrombus or mobile plaque
Favorable for CAS
Unfavorable
(Relative or absolute contraindications to CAS)

20. CAS for Stroke Prevention: Which pts
CAS for Stroke Prevention: Which pts? What type of arch and is it navigable?
Optimal - type I
~70%-75% of patients

21. Type 3 Arch
Increased manipulation- prolonged procedure time

22. Severe Proximal Tortuosity
As sheath introduction straightens proximal vessel, redundancy extends cephalad, causing kinking

23. CAS for Stroke Prevention: Which pts
CAS for Stroke Prevention: Which pts? Is Vascular Access straightforward?
Tortuosity or friable plaque or other? (e.g. disease or occlusion of aorta that might preclude safe access to the aortic arch)

24. Higher Risk pts for CAS Tortuous ICA: 90 degree take-off
120 degree prox. turn
Higher Risk pts for CAS
Excessive tortuosity

25. EPD
Kinking predictable!
Left ICA

26. Higher Risk for CAS: Calcification and Ulceration
Heavy concentric calcification

27. Do We Have the Optimal Devices? Closed- vs Open-Cell Stents
Carotid stents are expected to trap crushed, emulsified plaque and its contents.
Protégé
PRECISE®
Acculink
NexStent
Xact
Carotid Wallstent
Exponent

28. Cerebral Protection Strategies
Epic
Maveric
Empire
Armour

29. Optimal Therapy for symptomatic Disease
Reaching target outcomes:
Requires careful case selection…should choose patients based on whether they qualify for percutaneous intervention, NOT based on disqualification from CEA.
Also requires experienced operator
More data (and experience) are needed to discern ultimate role and appropriateness of each intervention in a given patient