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.

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 www.vivapvd.com

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

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

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

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

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?

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

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

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

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

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

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

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

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

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 2010:9:339-41.

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) 50:1049-53.

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

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)

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

Type 3 Arch Increased manipulation- prolonged procedure time

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

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)

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

EPD Kinking predictable! Left ICA

Higher Risk for CAS: Calcification and Ulceration Heavy concentric calcification

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

Cerebral Protection Strategies Epic Maveric Empire Armour

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