1. SVS Clinical Research Priorities: Carotid Disease John J Ricotta MD FACS

2. Background: Public Health Impact (AHA Heart Disease and Stroke Statistics 2011 Update, Circ 2011;123: e18-e209) 7M strokes, 13M silent infarctions 7M strokes, 13M silent infarctions 795k strokes/yr – 610k new, 185k recurrent - 87% (690k) ischemic (140-200k CAD) - 2/3 unheralded - 150k fatal (16.7% of all CVD) - 15-30% survivors permanent serious disabled, only 1/3 completely recover 795k strokes/yr – 610k new, 185k recurrent - 87% (690k) ischemic (140-200k CAD) - 2/3 unheralded - 150k fatal (16.7% of all CVD) - 15-30% survivors permanent serious disabled, only 1/3 completely recover 250-500 K TIA/yr – 17% stroke w/in 90 days 250-500 K TIA/yr – 17% stroke w/in 90 days Early RX of TIA/Stroke reduces death and disability from recurrence Early RX of TIA/Stroke reduces death and disability from recurrence

3. Background: Imaging CDUS preferred for initial imaging CDUS preferred for initial imaging No agreement on best imaging protocols CDUS, CTA, MRA, DSA No agreement on best imaging protocols CDUS, CTA, MRA, DSA Neck imaging not routinely incorporated into acute stroke protocols Neck imaging not routinely incorporated into acute stroke protocols No agreement on role of imaging in asymptomatic patients No agreement on role of imaging in asymptomatic patients No agreement on follow up protocols No agreement on follow up protocols

4. Background: Therapy CEA beneficial for Sx and Asx CS CEA beneficial for Sx and Asx CS CAS beneficial for Sx pts CAS beneficial for Sx pts CEA decreasing CAS increasing 86% /14% CEA decreasing CAS increasing 86% /14% CREST: CEA reduced stroke/death CAS reduced MI Composite endpoints equivalent CREST: CEA reduced stroke/death CAS reduced MI Composite endpoints equivalent 90% of Interventions on Asymptomatic pts. NNT 16-19 90% of Interventions on Asymptomatic pts. NNT 16-19 Role of BMT? Role of BMT?

5. CEA vs CAS Met Analysis (Murad et al JVS 2011;53:792-7)

6. Background: Economic Impact (AHA Heart Disease and Stroke Statistics 2011 Update, Circ 2011;123: e18-e209) Annual stroke Cost 40.8 Billion -direct costs 25.2 Billion Annual stroke Cost 40.8 Billion -direct costs 25.2 Billion Lifetime Cost / stroke $140,048 Lifetime Cost / stroke $140,048 CEA cost effective even Asx pts - low stroke rate, longevity and high cost of stroke CEA cost effective even Asx pts - low stroke rate, longevity and high cost of stroke CEA more cost effective than CAS d/t procedural costs ($4,000/ case) CEA more cost effective than CAS d/t procedural costs ($4,000/ case)

7. Background Economic Impact Carotid and Neuroimaging costs are a significant portion of health care costs Carotid and Neuroimaging costs are a significant portion of health care costs - CMS reimbursed 3m CDUS/yr - CT/ MRI cost likely much more Defining appropriate algorithms for case finding and follow up is important Defining appropriate algorithms for case finding and follow up is important Identifying imaging protocols that identify stroke prone lesions is important -avoid unnecessary Interventions in Asx pts. Identifying imaging protocols that identify stroke prone lesions is important -avoid unnecessary Interventions in Asx pts.

8. Current Evidence Review recent Guidelines from ASA/ACC/AHA and SVS to Identify clinical issues that require further study Review recent Guidelines from ASA/ACC/AHA and SVS to Identify clinical issues that require further study Review SVS Membership recommendations Review SVS Membership recommendations Issues divided based on several criterion - Resource Utilization - Patient Selection for Intervention - Comparison of Alternative Therapies - Conditions with little data to guide treatment Issues divided based on several criterion - Resource Utilization - Patient Selection for Intervention - Comparison of Alternative Therapies - Conditions with little data to guide treatment

9. Guidelines: Imaging No Benefit to population based Screening - bruit alone not an indication No Benefit to population based Screening - bruit alone not an indication High Risk screening may be indicated - smokers, PVD, CAD (L main), age >65, multiple factors increase yield High Risk screening may be indicated - smokers, PVD, CAD (L main), age >65, multiple factors increase yield F/U with disease or after intervention indicated but no agreement on intervals or what to do with pts who are “normal” after intervention F/U with disease or after intervention indicated but no agreement on intervals or what to do with pts who are “normal” after intervention

10. Guidelines: Imaging Plaque character, surface ulceration, “hits” on TCD, asymptomatic lesions on brain imaging all associated with increased stroke risk Plaque character, surface ulceration, “hits” on TCD, asymptomatic lesions on brain imaging all associated with increased stroke risk Impression but no evidence that severity (60-79 vs. 80-99) of Asymptomatic Stenosis is related to stroke risk Impression but no evidence that severity (60-79 vs. 80-99) of Asymptomatic Stenosis is related to stroke risk Duplex, CT and MR all utilized to describe plaque character but with inconsistent results Duplex, CT and MR all utilized to describe plaque character but with inconsistent results Silent on imaging protocols in acute stroke Silent on imaging protocols in acute stroke

11. Imaging in Acute Stroke Patients “Brain attack” protocols focus on MRI with intracranial MRA -neck MRA or carotid duplex is not standard “Brain attack” protocols focus on MRI with intracranial MRA -neck MRA or carotid duplex is not standard “Just in time” duplex not mentioned in patients with ANS, EXPRESS data shows expedited evaluation reduces recurrent Sxs “Just in time” duplex not mentioned in patients with ANS, EXPRESS data shows expedited evaluation reduces recurrent Sxs This is inconsistent with recommendation for early CEA in acute stroke patients This is inconsistent with recommendation for early CEA in acute stroke patients Selection of therapy depends on distribution of intracranial and extracranial disease Selection of therapy depends on distribution of intracranial and extracranial disease

12. Imaging Questions When is screening Asymptomatic Pts for CS indicated? When is screening Asymptomatic Pts for CS indicated? How do we define “stroke prone” lesions? How do we define “stroke prone” lesions? Impact of early duplex in TIA pts Impact of early duplex in TIA pts What imaging is needed in the acute stroke patient IC vs EC ? What imaging is needed in the acute stroke patient IC vs EC ? What follow up is appropriate for CS or after carotid intervention? What follow up is appropriate for CS or after carotid intervention?

13. Potential Studies Identify “high risk” subgroups to screen with CDUS Identify “high risk” subgroups to screen with CDUS Identify/ Compare reproducible, available techniques to identify plaque and surface characteristics to identify “high risk” lesions Identify/ Compare reproducible, available techniques to identify plaque and surface characteristics to identify “high risk” lesions Determine natural history of 60-79% vs 80-99% stenosis Determine natural history of 60-79% vs 80-99% stenosis Evaluate “just in time” imaging in TIA pts Evaluate “just in time” imaging in TIA pts Evaluate yield of routine neck imaging in acute stroke patients (race, age) Evaluate yield of routine neck imaging in acute stroke patients (race, age) Utility of post intervention imaging Utility of post intervention imaging

14. Guidelines: Patient Selection Intervention for Sx > 50%, Asx >60%, >70% provided AHA procedural guidelines met Intervention for Sx > 50%, Asx >60%, >70% provided AHA procedural guidelines met CEA preferred to CAS in good risk pts. CEA preferred to CAS in good risk pts. CAS preferred in High risk SX pts CAS preferred in High risk SX pts CAS an alternative in Sx and Asx pts within AHA guidelines CAS an alternative in Sx and Asx pts within AHA guidelines In Sx pts intervention preferred within 2 weeks of Symptoms In Sx pts intervention preferred within 2 weeks of Symptoms

15. Guidelines: Patient Selection Acknowledge the dysjunction of the “composite” endpoints of stroke, death, MI Acknowledge the dysjunction of the “composite” endpoints of stroke, death, MI Definition of “Medical High Risk” Definition of “Medical High Risk” Acknowledge need for Medical arm in Asymptomatic patients Acknowledge need for Medical arm in Asymptomatic patients Intervention for High Grade recurrent stenosis despite poor data Intervention for High Grade recurrent stenosis despite poor data

16. Guidelines Unanswered Questions Definition of “High Risk” CAS / CEA pts Definition of “High Risk” CAS / CEA pts Ideal stent, EPD Ideal stent, EPD Long term sequelae of “silent hits” on MRI, chemical MI Long term sequelae of “silent hits” on MRI, chemical MI Recommendations on combined carotid and coronary disease Recommendations on combined carotid and coronary disease

17. Patient Selection Questions Medical Treatment vs intervention in Asx pts. (2 ongoing trials underway) Medical Treatment vs intervention in Asx pts. (2 ongoing trials underway) Long term cognitive impact of MRI lesions Long term cognitive impact of MRI lesions How to reduce MI in CEA and Stroke in CAS How to reduce MI in CEA and Stroke in CAS What is contemporary CEA/CAS High Risk What is contemporary CEA/CAS High Risk When to intervene in restenosis When to intervene in restenosis Carotid interventions in CABG pts Carotid interventions in CABG pts

18. Potential Studies CAS/CEA/Med Rx in asymptomatic pts - can combine with lesion characterization CAS/CEA/Med Rx in asymptomatic pts - can combine with lesion characterization Long Term Cognitive Function CAS/CEA/BMT Long Term Cognitive Function CAS/CEA/BMT Intervention vs observation in Asx restenosis Intervention vs observation in Asx restenosis Role of Carotid Screening in CAD pts -identify “high yield” group Role of Carotid Screening in CAD pts -identify “high yield” group Revascularization Strategies in CABG pts -unilateral Asx >80%, b/l Asx >70%, Sx >50% ( evaluate aortic arch) Revascularization Strategies in CABG pts -unilateral Asx >80%, b/l Asx >70%, Sx >50% ( evaluate aortic arch)

19. Potential Studies How to improve results of Interventions - Role of CAD screening in Asx CEA pts How to improve results of Interventions - Role of CAD screening in Asx CEA pts - Role of anatomic selection in CAS -“Learning curve” in CAS - Role of anatomic selection in CAS -“Learning curve” in CAS - Influence of stent design, EPD type in CAS

20. Guidelines: Insufficient Data to Guide Treatment Intervention in acute stroke Intervention in acute stroke Crescendo TIA Crescendo TIA Stroke in Evolution Stroke in Evolution FMD - symptomatic and asymptomatic FMD - symptomatic and asymptomatic Carotid Dissection Carotid Dissection

21. Questions Define acute stroke pts who will benefit from urgent/emergent intervention -size infarct IC vs EC disease Define acute stroke pts who will benefit from urgent/emergent intervention -size infarct IC vs EC disease Treatment of SIE, Crescendo TIA Treatment of SIE, Crescendo TIA Treatment for FMD – sx and asx -observation, AP, AC, CAS Treatment for FMD – sx and asx -observation, AP, AC, CAS Carotid dissection – if/when to intervene, AC vs. AP Carotid dissection – if/when to intervene, AC vs. AP

22. Potential Studies Urgent (<48hrs) vs. Early (<2wks) intervention in acute stroke –role of brain imaging and arterial anatomy in selection Urgent (<48hrs) vs. Early (<2wks) intervention in acute stroke –role of brain imaging and arterial anatomy in selection FMD – Asx: Antiplt vs. observation Sx: Antiplt vs. CAS FMD – Asx: Antiplt vs. observation Sx: Antiplt vs. CAS Dissection – AC vs. AP vs. CAS in symptomatic pts Dissection – AC vs. AP vs. CAS in symptomatic pts Early intervention vs. Medical Rx for Crescendo TIA and SIE, selection factors Early intervention vs. Medical Rx for Crescendo TIA and SIE, selection factors

23. Priorities CAS/CEA/BMT in Asymptomatic pts CAS/CEA/BMT in Asymptomatic pts Optimal imaging protocols Optimal imaging protocols Improving results of Interventions Improving results of Interventions Management of Pts with combined disease, recurrent stenosis Management of Pts with combined disease, recurrent stenosis Management of Acute Neurological Syndromes Management of Acute Neurological Syndromes Unusual Conditions Unusual Conditions