Carotid Stenting: Unanswered Questions and Future Directions

1
Carotid Stenting Unanswered Questions and
Future Directions

• Rod Samuelson, Elad Levy, LN Hopkins
• University at Buffalo Neurosurgery
• October 2006

2
LN Hopkins, MD Potential Conflicts

• Consultant research support
• Boston Scientific, Cordis, Medtronic,
• Guidant
• Financial interests
• Boston Scientific EPI, Cordis, JJ, Micrus,
  Endotex, Access Closure Inc

3
Carotid StenosisWhat do We Know?

• In LOW RISK Patients
• CEA is of benefit (greater for Sx pts)
• CEA of more benefit with severe stenosis
• CEA of more benefit in elderly
• CEA must be done safely

4
Carotid StenosisWhat do We Know?

• In Asymptomatic Low Risk Patients
• CEA is better than medical therepy
• CEA prevents strokes in women (ACST)
• CEA prevents disabling strokes (ACST)
• CEA prevents fatal strokes (ACST)

5
Carotid StenosisWhat do We Know?

• In Elderly Patients
• Stroke risk is much higher in elderly pts
• CEA greatly benefits elderly low risk pts
• CEA risk is increased in elderly patients

6
Carotid StenosisWhat do We Know?

• Definition of High Risk for CEA
• CAS risk CEA in High Risk pts
• CAS CEA risk is higher in elderly pts and in
  symptomatic pts

7
Unanswered Questions

• Should we treat Symptomatic low risk pts with CAS
  or CEA?
• Embolic protection no/ yes/ what type?
• Which is better Open or Closed cell stents
• What training is best for CAS

8
Unanswered Questions

• What is High Risk for CAS ?
• Should we treat elderly pts with CAS ?
• Are high risk (CEA) pts at higher risk for stroke
  ??
• The 3 Rule ????

9
A Few Helpful Facts
10
Asymptomatic Carotid Stenosis and Risk of Stroke
Study (ACSRS)

• Asymptomatic Patients with Medical
• CoMorbidities And Severe Stenosis
• Stroke rate up to 6 per year !!

The 3 Rule does not apply to High Risk pts
Kakkos,Nicolaides et al Int Angiol 05, 24,
221-30
11
Elderly Patients(75-79)NASCET Analysis

• Absolute risk reduction(ARR) overall 17
• ARR in pts 75-79 30

12
Some Stroke Facts

• Only 1/3 of strokes are preceded by TIA
  Caplan et al
• Many TIAs are never diagnosed
• Castaldo, Tool et al, Arch neurol, 1997
• Many Stroke are never diagnosed

13
Stroke Facts

• Silent infarcts (CTMRI) noted in 12-70
  of asx pts
  (ACST) Halliday
• Silent infarcts seen in 15 of ACAS
  patients

14
Other Non Symptom Symptoms

• Neurocognitive function impaired in
  asymptomatic patients.
  Raabe, SIR March 06
• Dizzyness ???

15
High Risk CAS

• Not the same as for CEA
• Are CEA and CAS complementary ?
• What are identified CAS risk factors?
• How to make CAS SAFER ?

16
Current CAS Results (D/S/MI)High Risk Registries

• CAPTURE 6
• CREATE 6
• BEACH 5
• CABERNET 4
• CASES 5

17
Current CAS ResultsOutliers, But RPCT

• SPACE 7
• EVA 3S 10

18
CAPTURE 3700Post Market Surveillance
Primary Endpoint Summary
n(sx) 509 n(asx)3194 n(sx)284 n(asx)2656
19
CAPTURE STROKE COHORT Summary- Capture 3500
patients

• Overall stroke rate 4.8
• Major stroke rate 2.0
• Minor stroke rate 2.9
• Ipsilateral stroke rate 4.0
• Non-ipsilateral stroke rate 0.9 (18 of
  all strokes)

20
CAPTURE STROKE COHORT Summary of Strokes

• Stroke rate in high risk population is 4.8
• Major stroke rate 2.0
• Non-ipsilateral represents 18 of strokes of a
  cumulative 0.9 rate
• No non-ipsilateral strokes reported during the
  procedure
• 38 of strokes occurred after 24 hours
• 78 of strokes occurred post-procedure and
  post-discharge

21
CAPTUREGender Symptoms

• DSMI overall Sx pts 12.2 Asx 5.3 (.0001)
• DS (F Worse) Sx F lt80 vs Sx M lt80 (.03)

22
CAPTURE Post Market Registry3000 ptsFDA
Selection CriteriaOctogenarians

• Age gt 80 713/3000 pts(24)
• Independent predictors DSMI _at_ 30 days
• DSMI 9.4(gt80) vs 5.2(lt80)
• Calcification (mod) OR 1.39
• Predilitation for filter OR 3.22
  stroke alone OR 4.02
• Multiple stents OR 1.77 gt80 stroke
  alone OR3.14

23
CAPTURE STROKE COHORT Questions

• Why do many strokes occur after the procedure
  (78) or after 24 hours (38)? Would Closed
  Cell stents be better??
• Why do 18 occur in a vessel that has not been
  manipulated?
• Does the answer lie in?
• Arch Type, calcification and overall plaque
  morphology
• Improved technical equipment
• Medical therapy before and after the procedure

24
CREATE High Risk RegistryEV3 Stent Spider
Filter30 Day Results

• 30 day death, stroke and MI 6.2
• Major Stroke 3.5
• Hemorrhage 1.3
• Risk Factors
• Symptomatic carotid stenosis
• Renal failure
• Duration of filter deployment

25
SPACE TrialRPCT N1200

• Death, Stroke and MI - 30 day
• CAS 6.8
• CEA 6.3
• p 0.09
• CEA better in older patients

26
CAS Risk Factors

• 1)Symptomatic lesion
• 2)Sx gt age 80
• 3)Renal Failure
• 4)Multiple stents
• 5)Duration Filter deployment
• 6)Pre dilitation
• 7)Tortuous/calcified arteries

27
CASNon Predictors of Risk

• Sex ?? CAPTURE
• Calcification
• Residual stenosis
• Filter
• Contralateral occlusion
• Smoking
• Diabetes
• Statins

28
Newer ResultsWhat Do They Mean?

• Endarterectomy versus Stenting in Patients with
  Symptomatic Severe Carotid Stenosis
• EVA-3S Trial
• New England Journal of Medicine
• October 19, 2006

29
EVA-3S Trial Design

• Prospective, Multicentered, Randomized
• Sponsored by French Ministry of Health
• Inclusion
• Symptomatic Carotid Stenosis gt 60
• Patients equal candidate for either option
• Primary endpoint
• Any stroke or death within 30 days
• Stopped prematurely by safety monitoring
  committee after 527 patients were enrolled

30
EVA-3S Trial Results

• 30 Day rate of any stroke or death
• Endarterectomy 3.9
• Carotid Stent 9.6
• Relative Risk of 2.5 (95 CI 1.2 to 5.1)
• 30 Day rate of disabling stroke or death
• Endarterectomy 1.5
• Carotid Stent 3.4
• Relative Risk of 2.2 (95 CI 0.7 to 7.2)
• Not statistically significant

31
EVA-3S Trial Results

• 6 month rate of any stroke or death
• Endarterectomy 6.1
• Carotid Stent 11.7 (p 0.02)
• Conclusion
• For symptomatic patients (gt60) with acceptable
  surgical risk, rates of death and stroke were
  lower with CEA than with stenting

32
EVA-3S Trial Limitations

• Distal protection was only strongly
  recommended after February 2003 (50 trial
  duration)
• 30 day stroke or death
• Without DEP 25 (5 of 20)
• With DEP 7.9 (18 of 227)
• If 7.9 rather than 9.6 is used
• Relative Risk 2.0 (p 0.07)

33
EVA-3S Trial Limitations

• Rates of MI were not assessed
• (Reduced rate of MI was one source of benefit
  identified in the SAPPHIRE Trial)
• Only 30 day and 6 month follow up
• (Despite trial ongoing since 2000)

34
EVA-3S Trial Limitations

• Experience bias
• Vascular surgeons
• Required 25 CEAs in the year prior to study entry
• Endovascular physicians
• Required 12 carotid stents or 35 supra-aortic
  stents with at least 5 carotid stents
• Or, Allowed to receive training and credentialing
  under supervision as they enrolled patients in
  the trial
• Allowed to use new stents after only two cases

35
EVA-3S Trial Limitations

• Enrollment Bias?
• Total CEA case volumes were not discussed
• Estimated 15 or less of all patients randomized
• Thirty hospitals
• Assuming only 1 vascular surgeon per hospital
  with the enrollment criteria minimum 25 cases/yr
• 4.75 years of enrollment 3562.5 patients

36
Complementary Techniques

• Before EVA-3S, Most evidence showed Stents are
  not inferior in efficacy and safety to CEA.
• Are there patient groups in which stents are
  superior?
• Answer begins with high surgical risk

37
What is the long term durability?
38
Long Term Durability

• Major events at 3 years
• Stent 25.5 vs. CEA 30.3 (p0.231)
• Death at 3 years
• Stent 20.0 vs. CEA 24.2 (p0.280)
• Ipsilateral stroke at 3 years (All stroke 30
  days)
• Stent 7.1 vs. CEA 6.7 (p0.945)
• Need for same vessel revascularization
• Stent 3.0 vs. CEA 7.1 (p0.084)

SAPPHIRE
39
Long Term Durability

• Need for revascularization
• 2.2 at 1 year

Doppler Ultrasound Follow Up
ARCHeR
40
What will CREST teach us that we dont already
know?

• CREST Randomized CAS vs. CEA
• Started in 2000, gt100 centers
• Plans to enroll 2500 patients
• Enrollment- around 1700
• 1387 lead-in cases
• 789 carotid stents reported in November 2004
• 30 day stroke and death 4.6
• 30 day MI 1.1

41
What will CREST teach us that we dont already
know?

• Differences from EVA-3S
• Distal Embolic Protection
• MI rates are monitored
• Dual antiplatelet therapy in all patients
• Long term follow up
• More rigorous interventionalist credentialing
• CREST is now more important than ever
• Challenges to Recruitment are present

42

• Conclusions
• CAS and CEA are complementarythe patient must
  have every technical option
• Asymptomatic patients deserve treatmentwe dont
  know which is best yet
• Low-risk patients should be enrolled in further
  trials! CREST, ACT 1
• We are beginning to understand which pts are at
  high risk for CAS.AVOID them!!!!

43
Future PerspectivesThe War Against StrokeHow
Are We Doing??
44
Who Will Treat Acute Stroke?

• 750,000 CVAs per year and growing
• 250 neurointerventionalists
• 60 endovascular neurosurgeons
• 5 endovascular neurologists
• 5,000 interventional cardiologists

45
(No Transcript)
46
How Do We Get There ?

• Training
• Technology
• Collaborating

47
Barriers

• Societal
• New Anatomy
• Technology

48
CollaborationSubspecialty Strengths

• Neurology
• Radiology
• Vascular surg
• Vascular med
• Cardiology

• End organ cognitive
• Imaging/cath skills
• Own CEA market
• Cognitive/imaging
• Cath/angioplasty skills
• Clinicians
• Industry partners
• Clinical research

49
We Will Win the War on StrokeAndCardiologists
Will Treat Stroke
50
Simulator Training Model

• Commercial Pilot
• Mandatory yearly training
• 60 hours simulated instrument training
• 60 hours actual instrument training

• Col. Chester Griffin
• Director, Simulator Training
• AW Certification - USAF

51
Flight SimulationThree Components

• Tactile (haptics)
• Procedural
• Complications

Sound Familiar ??
52
Virtual Reality Training Improves Operating Room
Performance

• Seymour, Gallagher, et al.
• Annals of Surgery 2002.
• Randomized, Double-Blinded Study
• 16 surgical residents
• Assessment during laparoscopic cholecystecomy by
  surgeon-investigator blinded to the residents
  training status.

53
Results

• Simulator Trained
• 29 less time for dissection

• Traditionally Trained
• Gallbladder injury and burn of non-target tissue
  5 x more frequent
• 6 x more errors
• More frequent failure to make progress

54
Mentice Simulator
55
Illustrative Case

• 27 year old female
• Cesarean delivery 8 weeks prior
• Ground level fall and head impact
• No LOC, No seizure
• Acute onset right neck and head pain
• Left upper extremity weakness
• Slurred speech

56
Illustrative Case

• Meds Oral contraceptives
• In ED NIHSS 11
• Left facial weakness, dysarthria, left upper
  extremity weakness, left sided anesthesia
• Head CT no acute trauma
• Head CT perfusion

57
Original CT Perfusion
Time to Peak
58
Emergent Angiogram
59
Acute RICA occlusion

• Heparin 4000
• ACT gt250

60
Microcatheter Injections
Nautica microcatheter Transcend exchange
microwire
61
Carotid Stent

• BMW wire to supraclinoid ICA
• Xpert stent 4 x 40
• Still occluded proximally
• Xpert stent 5 x 40
• No overlap
• Xpert stent 5 x 30

62
Acute MCA Occlusion
63
Merci Clot Retrieval
Integrilin
64
Neuroform Stent for Failed Merci

• Renegade microcatheter
• Neuroform (4 x 20) loaded into
  microcatheter

65
Follow Up CT perfusion
66
Two Month Follow Up

• Mild Dysmetria
• Left Arm Paresthesias

67
Thank You!