Carotid Artery Stenting Today:���A Few Updating Remarks

Camilo R. Gomez, MD, MBA Director, Alabama Neurological Institute

Birmingham, Alabama

Carotid Stenting Disclaimer & Warning

Company Relationship Pharmaceutical BMS-Sanofi-Aventis Abbott Laboratories Parke-Davis Devices Alsius Corporation Boston Scientific Guidant Corporation CoAxia

Consultant. Speaker. Investigator. Speaker. Investigator. Investigator

Consultant. Speaker. Investigator. Consultant. Speaker. Investigator. Consultant. Speaker. Investigator. Consultant. Speaker. Investigator.

Many Statements Not FDA-Approved

Carotid Stenting ���Why Should We Even Consider This?

Carotid Stenting ���When We Can Do This?

Avg = 15 minutes

Carotid Stenting ���In Expert Hands… …It Could Not Be Simpler

 Local Anesthesia  No Sedation  Same Day Discharge (!)

Carotid Stenting���NASCET: Ipsilateral Stroke (18 mo.)

 Essentially Less than 80 years of age

 No Cardiac Arrhythmias  No Organ Failure  Less than 25% Had:

 Diabetes  Hypercholesterolemia  Angina

NASCET. Stroke 1991; 22:711.

Carotid Stenting���NASCET: The Best Patients

 Cranial Nerve Injury = 7.6%  Wound Hematoma 5.5%  Wound Infection = 3.4%  Myocardial Infarction = 0.9%  CHF = 0.6%  Arrhythmia = 1.2%  Other Cardiovascular = 1.2%

NASCET. NEJM. 1991; 325:445-53

Carotid Stenting���NASCET: Other Surgical Complications

 659 Patients with Contralateral Pathology

 Risk of Stroke & Death:  Contralateral Mild --> 4.0%  Contralateral Moderate --> 5.1%  Contralateral Occluded --> 14.3%

 Contralateral Occlusion Hazards Ratio --> 2.11 - 2.18

Gasecki et al J NSG. 1995; 83: 778

Carotid Stenting���NASCET: Predictors of Stroke and Death

 Decreased Odds:  Ocular Symptoms Only (0.49)

  Increased Odds:  Women (1.44)  SBP >180 (1.82)  PVD (2.19)  Contral. Occl. (1.91)  Siphon Sten. (1.56)  ECA Sten (1.61)

Rothwell et al. BMJ 1997; 315:1571

Carotid Stenting���Predictors of Stroke & Death from CEA

 Surgical Group (n = 1807)  Major Stroke 30d = 6.6%  Major Stroke+Death 30d = 7.0%

 Medical Group (n=1211)  Major Stroke 30d = 4.8%  Major Stroke+Death 30d = 4.8%

ECST. Lancet 1998; 351: 1379-1387

Carotid Stenting���Carotid Endarterectomy: ECST

 113,300 Medicare Patients Undergoing CEA  Institutions:

 “Trial” Hospitals  “Non-Trial” Hospitals (By Volume of CEA)

 Perioperative Mortality:  “Trial” --> 1.4%  “Non-Trial” --> 1.7% - 1.9% - 2.5%

Wennberg et al. JAMA 1998; 279:1278

Carotid Stenting���Medicare Data on CEA

Carotid Stenting ���Medicare Coverage: The Process

Carotid Stenting���SAPPHIRE (30 Days)

Yadav J et al. N Engl J Med 2004;351:1493-1501

Carotid Stenting��� SAPPHIRE (365 Days)

Yadav J et al. N Engl J Med 2004;351:1493-1501

  30 Day Complication rates:  Mortality = 41 (0.86%)  Minor Stroke = 129 (2.72%)  Major Stroke = 71 (1.49%)  All Stroke = 192 (3.94%)  All Stroke + Death = 241 (5.07%)

  Stroke = 1.42% over 6-12 months  Restenosis rate = 1.99 % & 3.46% (6 & 12

months)

Wholey M et al. Cathet Cardiovasc Interv 50:160. 2000

Carotid Stenting���International CAS Registry

Carotid Stenting��� ARCHeR Trials

 CREST:  Randomized vs. CEA  2500 Symptomatic or Asymptomatic

 ACT I  Randomized vs. CEA  1858 Asymptomatic

 VIVA  Single Group  Symptomatic & Asymptomatic

Carotid Stenting Current Studies: Phase III

 691 Cases (December 2003)  Up to 20 cases per operator  Peri-procedural Stroke & Death:

 3.1% for Asymptomatic Patients (n=395)  4.3% for Symptomatic (n= 191)  3.5% Overall

Carotid Stenting���CREST: Lead-In Phase

 SONOMA  Single Group Registry  1650 Patients

 CREATE PAS  Single Group Registry

 CAPTURE 2  Single Group Registry  10000 Patients

Carotid Stenting Current Studies: Phase IV

 Sponsor: Guidant Corporation  Design:

 Phase IV Study (Post-Market)  315 Operators in 137 Hospitals

 Enrollment to Date: >4000 High-Risk Patients  Preliminary Results (March 2006)

 Patients: 2500  Primary Outcomes:

 30-day Death, Stroke and MI = 5.7%  30-day Major Stroke & Death = 2.5%

Carotid Stenting Recent Reports: Preliminary CAPTURE Data

  4,111 Patients in 150 Sites  CAPTURE 2: 1,987 Patients (On-Going)  EXACT: 2,124 Patients (Completed)

 Composite 30-day Stroke and Death

Carotid Stenting Recent Results: CAPTURE 2 and EXACT

Stroke & Death (SX)

Stroke & Death (ASX)

Stroke & Death (ALL)

CAPTURE 2 6.0% 3.1% 3.8%

EXACT 7.3% 3.0% 4.0%

Courtesy of Gray, WA. TCT October 23, 2007

 Design: Phase III, Open label, Randomized CAS vs. CEA

 Enrollment: 1200 Symptomatic Patients in 35 Centers

 Primary Outcomes:  30-day Ipsilateral Stroke or Death

Carotid Stenting Recent Reports: SPACE

Carotid Stenting Recent Reports: SPACE

End Point Carotid Stenting, n (%)

Carotid Endarterectomy, n (%)

Odds Ratio (CAS vs CEA) (95% CI)

Primary end point 41 (6.84) 37 (6.34) 1.09 (0.69 – 1.72)

Ipsilateral ischemic stroke 39 (6.51) 30 (5.14) 1.26 (0.77 – 2.18)

Ipsilateral intracerebral bleeding 1 (0.17) 5 (0.86) 0.19 (0.004 – 1.74)

Death 4 (0.67) 5 (0.86) 0.78 (0.15 – 3.64)

Carotid Stenting��� Cochrane Review of Evidence

Carotid Stenting��� Cochrane Review of Evidence

Carotid Stenting��� Cochrane Review of Evidence

Carotid Stenting���Growth in Carotid Stenting: A Problem?

Source: Roubin, G.S.

Carotid Stenting Market Estimates (Millions)

2004 2005 2006 2007 2008

HRI, Dec 2003 $41.2 $92.3 $119.3 $145.2 $162.8

Morgan Stanley $23 $62 $74 $292 $398

Bernstein Research $5 $31 $53 $110 n/a

Carotid Stenting ���Medicare Coverage: The Process

Carotid Stenting ���Medicare Coverage: Facilities

http://www.cms.hhs.gov/MedicareApprovedFacilitie/CASF/

Carotid Stenting ���Market Performance

Carotid Stenting ���Acceptance by Surgical Community

Carotid Stenting ���Acceptance by Surgical Community

Carotid Stenting Paradoxical Created Behavior

“The friend of my adversity I shall always cherish most. I can better trust those who helped to relieve the gloom of my dark hours than those who are so ready to enjoy with me the sunshine of my prosperity.”

Ulysses. S. Grant

CAS Stenting���Filters for Embolic Protection

CAS Stenting���Global Impact of Protection

Roubin et al Circulation. 2001 Jan 30;103(4):532-7

Carotid Stenting��� Our Long-Term Experience

Carotid Stenting���Single Center Long-Term Experience

“No Equipment is a Substitute for Good Technique!”

CAS Stenting���Operator Skill’s: Sine Qua Non

Updated on 04/13/04

Protection Devices

Carotid Stenting���Perspective on Operator’s Skills

N 108 113

Age 66.7 70.0* Male 66% 62% Caucasian 90% 98% HTN 69% 81%* Diabetes 34% 28% MI 19% 28% CHF 7% 4% Baseline % stenosis 76% 75%

* p < 0.05

Carotid Stenting ���Wallstent Trial: Results

* p=0.036 ** p=0.049

Carotid Stenting ���Wallstent Trial: Major End-Points

 Sponsor: Assistance Publique – Hospitaux de Paris

 Design: Phase III, Open label, Randomized CAS vs. CEA

 Expected Enrollment: 872 Symptomatic Patients  Enrollment: 527 (September 2005) in 30 Centers  Primary Outcomes:

 30-day Stroke or Death  2-4 year stroke, death or ipsilateral stroke

 Secondary Outcomes: Numerous

Carotid Stenting Recent Reports: EVA3S

Mas J et al. N Engl J Med 2006;355:1660-1671

Carotid Stenting Recent Reports: EVA3S

 Operator’s Experience  Surgeons -> At Least 25 CEA Previous Year  Interventionists -> 12 CAS or 5/35 Supra-aortic ->

“No Difference (10% vs 12.3%)”  Technique:

 Antiplatelet Therapy “Recommended” (83-85% on Dual)

 Single device vs. Multiple devices (5/7)

Carotid Stenting EVA3S Commentary

Carotid Stenting ���Credentialing, Experience and Learning Curve

Carotid Stenting ���Beware of Guidelines!!

The Growth of Intellectual Communism

Carotid Stenting���Surgically Inaccessible Lesions

Carotid Stenting���Non-Atherosclerotic Pathology: FMD

Carotid Stenting���Non-Atherosclerotic Pathology: Radiation

Carotid Stenting���Reconstructive Stenting

Carotid Stenting���Reconstructive Stenting

 History:  75 y.o. woman  Recurrent Left Side Weakness  One Episode of Right Side Weakness

 Physical Examination:  No Deficits  Loud Bruits

Carotid Stenting CASE 1: Transient Ischemic Attacks

Carotid Stenting Final Thought

The Warrior Creed

Wherever I go, everyone is a little bit safer because I am there.

Wherever I am, anyone in need has a friend.

Whenever I return home, everyone is happy I am there...

...It's a better life! Robert L. Humphrey, J.D.