0. The Current Carotid Data Supports Broader Indications in all Categories
William A. Gray MD
Director of Endovascular Services
Associate Professor of Clinical Medicine

1. William A. Gray, MD DISCLOSURES Consulting Fees
AccessClosure, Inc., CoAptus, Inc., Mercator MedSystems, Inc., Ovalis, Inc., Paragon Medical, Inc., Pathway Medical Technologies, Inc., Sage Medical, Inc.
Grants/Contracted Research
Atritech, Inc., Cordis, a Johnson & Johnson company, CREST/ National Institutes of Health, W.L. Gore & Associates, Inc.
Ownership Interest (Stocks, Stock Options or Other Ownership Interest)
AccessClosure, Inc., CoAptus, Inc., Ovalis, Inc., Paragon Medical, Inc., Pathway Medical Technologies, Inc., Sage Medical, Inc.

2. AHA 1998 CEA Guidance Document
Patients With Asymptomatic
Carotid Artery Disease
For patients with a surgical risk <3% and life expectancy of at least 5 years:
Proven indications: Ipsilateral carotid endarterectomy is acceptable for stenotic lesions (<60% diameter reduction of distal outflow tract with or without ulceration and with or without antiplatelet therapy, irrespective of contralateral artery status, ranging from no disease to occlusion [Grade A recommendation])
Biller J, Feinberg WM, Castaldo JE, Whittemore AD, Harbaugh RE, Dempsey RJ, Caplan LR, Kresowik TF, Matchar DB, Toole JF, Easton JD, Adams HP Jr, Brass LM, Hobson RW 2nd, Brott TG, Sternau L. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a Special Writing Group of the Stroke Council, American Heart Association Circulation Feb 10;97(5):501-9.
Surgical endarterectomy has never, to date, demonstrated outcomes consistent with AHA guidelines within a prospective, neurologically-controlled, multi-center, adjudicated critical assessment of high surgical risk patients
These recommendations were based, in large part, on the results of the ACAS trial which demonstrated a benefit of CEA over medical Rx with a perioperative stroke and death rate of 2.7% in a low surgical risk cohort under 75 years

3. NY State Registry Results State of the state of CEA
Stroke. 2009;40:

4. Validation of high-risk
CEA subsets.

5. Conclusions from these recent data
Although limited in terms of surveillance for events (retrospective, not neurologist evaluated):
Confirmatory data on the outcomes after CEA, though probably underestimates events
Clearly identifies subgroups at increased risk

6. What do we know about stenting in 2010?

7. EVA-3S: long-term CAS stroke prevention
Any ipsilateral stroke
Any stroke
Any stroke or death

8. SPACE: long-term CAS stroke prevention
Ipsilateral stroke and
vascular death
30-day stroke/death
plus ipsilateral stroke
to 2 years

9. Latest devices and their data: all-comers N>1000 patients
Lumen/Invatec Fibernet
30 day MAE: 3.0%
WL Gore Flow Reversal System
30 day MAE: 3.7%
Abbott Vascular Gen V Emboshield
30 day MAE: 1.8%
Invatec ARMOUR:
30 day MAE: 2.7%

10. Incidence of stroke and death in high risk carotid stent IDE trials: 2002-2009 (n>4000)

11. SAPPHIRE WW: 30 day major adverse events Asymptomatic vs. Symptomatic
6% AHA Sx
3% AHA
Asx
P=NS
TEXT SLIDE
P=0.0010
P=0.0003
P=0.0005
P=0.0286
MAE defined as any death, MI or stroke

12. Never before seen outcomes in surgical high risk: EXACT and CAPTURE 2 30-day Death and Stroke
From Lugene:
These are confirmed as the correct hierarchy label. The section below is from the statistics discussions
From PROTECT sample size decision.
The 30-day MAE rate from this trial will be compared to a pre-specified value of 12.0%. The pre-specified level for comparison is based on an examination of the peer-reviewed literature in a similar high-risk patient population (ref. 30-day MAE rates reported from the following trials: SECuRITY, SAPPHIRE, ARCHeR, BEACH, and MAVErIC). Relative to the range of reported 30-day MAE rates from the literature, the pre-specified level of 12.0% is 3.74 percentage points above the maximum reported rate. The difference of 3.74 percentage points represents ~45% of the maximum reported 30-day MAE rate from the literature, and approximately 58% of the arithmetic average 30-day MAE rate reported among all 5 studies. *
EXACT (N=2145)*
CAPTURE 2 (N=4175)
Combined (N=6320)
EXACT (N=213)
CAPTURE 2 (N=548)
Combined (N=761)
EXACT (N=1931)
CAPTURE 2 (N=3627)
Combined (N=5558)
Hierarchical- Includes only the most serious event for each patient and
includes only each patient first occurrence of each event.

13. CAS beats AHA guidelines: never seen with CEA
Symptomatic patients
N=589
5.3
2.2
1.0
1.4
3.1 1 2 3 4 5 6 7 8
Death/Stroke
Death/Major Stroke
Death
Stroke Minor (3.1%)
Stroke Major (1.4%)
(%) Subjects 6%
AHA guideline
EXACT/CAPTURE 2 (combined): 30-day major adverse events symptomatic patients <80 years
From Lugene:
These are confirmed as the correct hierarchy label. The section below is from the statistics discussions
From PROTECT sample size decision.
The 30-day MAE rate from this trial will be compared to a pre-specified value of 12.0%. The pre-specified level for comparison is based on an examination of the peer-reviewed literature in a similar high-risk patient population (ref. 30-day MAE rates reported from the following trials: SECuRITY, SAPPHIRE, ARCHeR, BEACH, and MAVErIC). Relative to the range of reported 30-day MAE rates from the literature, the pre-specified level of 12.0% is 3.74 percentage points above the maximum reported rate. The difference of 3.74 percentage points represents ~45% of the maximum reported 30-day MAE rate from the literature, and approximately 58% of the arithmetic average 30-day MAE rate reported among all 5 studies.
Hierarchical- Includes only the most serious event for each
patient and includes only each patient first occurrence of each event. 13

14. CAS beats AHA guidelines: never seen with CEA
2.9
1.1
0.8
0.6
1.8 1 2 3 4 5 6 7 8
Death/Stroke
Death/Major Stroke
Death
Stroke Minor (1.8%)
Stroke Major (0.6%)
(%) Subjects 3%
AHA guideline
EXACT/CAPTURE 2 (combined): 30-day major adverse events asymptomatic patients <80 years
Hierarchical- Includes only the most serious event for each
patient and includes only each patient first occurrence of each event. 14

15. CAS beats AHA guidelines for all categories of high risk
Combined EXACT/CAPTURE 2: 30-day Major Adverse Events in Anatomic and Physiologic High Risk in Patients <80 years
% Death and stroke

16. Future Data Sets CREST: February 2010
ACT I: Lead-in phase in normal risk patients
Event
30 days, N=118
Death, Stroke, and MI*
1.7%
All Stroke and Death*
Major Stroke and Death*
0.0%
Death
All Stroke
Major Stroke
Minor Stroke MI

17. SPACE: sub-group analysis favors CAS

18. Conclusion
Based on current CAS data, and as compared to “state of the art CEA” there is justification to expand both indications and coverage to at least that of CEA