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

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.

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. 1998 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

NY State Registry Results State of the state of CEA Stroke. 2009;40:221-229

Validation of high-risk CEA subsets.

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

What do we know about stenting in 2010?

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

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

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%

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

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

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.

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

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

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

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

SPACE: sub-group analysis favors CAS

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