1 carotid artery stenting with emboli protection pma # p030047 cordis presentation sidney a. cohen,...

1

CAROTID ARTERY CAROTID ARTERY STENTING WITH EMBOLI STENTING WITH EMBOLI

PROTECTIONPROTECTION

PMA # P030047

Cordis PresentationSidney A. Cohen, M.D., Ph.D.

Group Director, Clinical Research

2

REQUESTED INDICATION REQUESTED INDICATION

• The Cordis [Carotid Stent System is] indicated for use in the treatment of carotid artery disease in high-risk patients. High-risk is defined as patients with neurological symptoms (one or more TIA’s or one or more completed strokes) and >50% atherosclerotic stenosis of the common or internal carotid artery by ultrasound or angiogram;

and • Patients without neurological symptoms and >80%

atherosclerotic stenosis of the common or internal carotid artery by ultrasound or angiogram.

• Symptomatic and asymptomatic patients must also have

one or more condition(s) that place them at high-risk for carotid endarterectomy.

3

AGENDAAGENDA• Project Overview & CAS Background

• Description of Devices

• Overview of PMA Clinical Data (Total of 1619 Pts)

1. Non-Randomized CAS Clinical Trials – Supportive data• CASCADE (European) Study• US FEASIBILITY Study

2. SAPPHIRE Pivotal Trial – Ken Ouriel, M.D.

• Randomized Arm: CAS vs. CEA

• Non-Randomized Arms: CAS and CEA

• Overview of Training

• Post-Market Surveillance Study

4

PROJECT OVERVIEWPROJECT OVERVIEW

• US FEASIBILITY Study start date - September 1998

• SAPPHIRE Pivotal Study start date – August 2000

• PMA filed on October 8, 2003– Achieved primary endpoint of non-inferiority of CAS to CEA for 1-year

– CAS - improved outcomes for MI and re-interventions with a significant decrease in cranial nerve injuries

– Sustained benefit of CAS treatment demonstrated through 3-years follow up

• PMA granted Expedited Review Status November 14, 2003– Significant therapeutic advance

5

BACKGROUNDBACKGROUNDStroke & Carotid DiseaseStroke & Carotid Disease

• >700,000 strokes occur annually in the U.S.1

• Stroke is the third leading cause of death with an estimated 164,000 deaths per year 1

• Up to 30% of strokes are caused by carotid artery disease2

• Stroke is the number 1 cause of disability in the U.S. 1

• Health care costs for stroke in excess of $53.6 billion/year1

• Over 50% of people under age 65 who have a stroke die within 8 years1

• Older population with co-morbid disease1

1. Heart Disease and Stroke Statistics – 2004 Update, American Heart Association 2. ACAS Executive Committee JAMA 273:1421-1428, 1995

6

BACKGROUNDBACKGROUNDCarotid EndarterectomyCarotid Endarterectomy

• 50 year history of technique development and refinement • CEA is the current interventional standard of care in

treating carotid artery disease to reduce the risk of stroke

• Up to 200,000 CEAs performed per year in the U.S.1

• Estimated that 20% of CEAs are performed on “high surgical-risk” patients annually in the U.S.2

• High surgical risk defined:

– Anatomic - increased procedure risk

– Medical Co-morbidities - increased risk MI and death

1. Heart Disease and Stroke Statistics – 2004 Update, American Heart Association 2. Ouriel et al., J Vasc Surg 33:728-732, 2001

7

BACKGROUNDBACKGROUNDCarotid Endarterectomy - contCarotid Endarterectomy - cont

• Randomized clinical studies

– Superiority of CEA vs. best medical therapy • NASCET1

– Symptomatic >50% diameter stenosis

• ACAS2 – Asymptomatic >60% diameter stenosis

• ECST3


• VA Cooperative Study4


• “Standard of Care” for interventional treatment of symptomatic and asymtomatic carotid artery disease

1. NASCET Trial Collaborators NEJM 325:445-453, 1991 2. ACAS Executive Committee JAMA 273:1421-1428, 1995 3. Rothwell et al., Stroke 34: 514-523, 2003 4. Hobson et al., NEJM 328:221-227, 1993

8

TYPE OF PATIENTS CURRENTLY TYPE OF PATIENTS CURRENTLY TREATED WITH CEATREATED WITH CEA

CEA treatment of patients clearly extends beyondNASCET/ACAS inclusion criteria:

– NASCET/ACAS studied a relatively healthy subset of patients:

• ACAS screened 25 to enroll 1 patient1

• NASCET 1 out of every 3 treated patients enrolled1

– Patients considered high risk for CEA as defined by trial ineligibility comprise up to 50% of patients in published series:

• Ochsner Clinic – 46.2%2

• CCF Registry – 19.4%3

1. Wennberg et al., JAMA 279:1278-1281, 1998. 2. Leporre et al., J Vasc Surg 34: 581-586, 2001.

3. Ouriel et al., J Vasc Surg 33: 728-732, 2001.

9

NASCET/ACAS EXCLUSION CRITERIANASCET/ACAS EXCLUSION CRITERIA

• Anatomic Risks• Tandem lesions • Previous CEA• Radiation therapy to

neck (ACAS)• Status post radical neck

dissection

• Medical Co-morbidities• Age >79• Previous CVA with profound deficit• MI within 6 months (NASCET)• Unstable angina• Atrial fibrillation• Symptomatic CHF• Valvular heart disease• Cancer with <50% 5 year survival• Renal/pulmonary/liver failure

10Wennberg, et al., JAMA, 279: 1278-1281, 1998

CEA MORTALITYCEA MORTALITY113,000 Medicare Patients (1992-1993)

0.1

0.6

1.4

1.7

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

ACAS NASCET Trial Hospitals Non-trialHospitals

30-Day Follow up

Mo

rtal

ity

%

11

PUBLISHED 30-DAY CEA EVENT RATESPUBLISHED 30-DAY CEA EVENT RATES

0

1

2

3

4

5

6

Death Stroke Death/Stroke

Ochsner Registry

Ohio Registry

NY Registry Sx

NY Registry Asx

%

1. Leporre et al., J Vasc Surg 34:581-586, 2001. 2. Cebul et al., JAMA 279:1282-1287, 1998

3. Halm et al., Stroke 34: 14264-1472, 2003

1

2

3

3

12

IN-HOSPITAL CEA OUTCOMES IN-HOSPITAL CEA OUTCOMES US ACADEMIC CENTERSUS ACADEMIC CENTERS

• Retrospective analysis• 1160 patients• 12 academic centers in US• 1988-90• In-hospital Death + MI +Stroke

McCrory DC et al. Stroke 1993;24:1285-1291

Dea

th +

MI +

Str

oke

6.9%

11.8%

9.5% 9.9%

0%

4%

8%

12%

All >75yrs Sx Angina

13

IN-HOSPITAL CEA OUTCOMES IN-HOSPITAL CEA OUTCOMES US ACADEMIC CENTERSUS ACADEMIC CENTERS

McCrory DC et al. Stroke 1993;24:1285-1291

Dea

th +

MI +

Str

oke

6.9%

11.8%

9.5% 9.9%

0%

4%

8%

12%

All >75yrs Sx Angina

2.10%

4.80%

3.40%

1.40%

0%

1%

2%

3%

4%

5%

Death Non-fatal

Stroke

Death& Non-

fatalStroke

MI

14

PERCENT ASYMTOMATIC PATIENTS PERCENT ASYMTOMATIC PATIENTS UNDERGOING CEA IS UP TO 75%UNDERGOING CEA IS UP TO 75%

0

10

20

30

40

50

60

70

80 Ohio Registry

Ochsner Clinic

CCF Registry

NY Registry

1998 2001 2001 2003

%

1. Cebul et al., JAMA 279:1282-1287, 1998 2. Leporre et al., J Vasc Surg 34:581-586, 2001

3. Ouriel et al., J Vasc Surg 33: 728-732, 2001 4. Halm et al., Stroke 34: 14264-1472, 2003

1

2

3

4

Chambers New England Journal of Medicine. 315(14):860-5, 1986Norris Stroke. 22(12):1485-90, 1991Mendelsohn & Yadav, Management of Atherosclerotic Carotid Disease, Remedica Publishing, 2000

6

5

4

3

2

1

00-19% 20-29% 30-39% 40-49% 50-59% 60-69% 70-79% 80-89% 90-99%

Str

oke

Inci

denc

e (%

)

Carotid Artery Stenosis

INCIDENCE OF STROKE AT 360-DAYSINCIDENCE OF STROKE AT 360-DAYS

Asymptomatic Patients

16

• In US, standard of care for interventional treatment includes:

– NASCET/ACAS eligible & ineligible patients– Symptomatic and asymptomatic patients– Higher risk patients

• Anatomic• Medical Co-morbidities

• SAPPHIRE trial studied patients who currently are referred for treatment of their carotid disease

TYPE OF PATIENTS CURRENTLY TYPE OF PATIENTS CURRENTLY TREATED WITH CEATREATED WITH CEA

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RATIONALE FOR TREATMENT OF RATIONALE FOR TREATMENT OF “HIGH SURGICAL-RISK” PATIENTS“HIGH SURGICAL-RISK” PATIENTS

• Initial evaluation of new technology (CAS) in cohort of patients where CEA is technically demanding

– Anatomic: difficult access that may lead to local tissue and nerve injury

– Medical Co-morbidities: patients less tolerant of general anesthesia & surgery

• CAS studied as an alternative and less invasive method of therapy

18

AGENDAAGENDA

• Project Overview & CAS Background

• Description of Devices • Overview of PMA Clinical Data (Total of 1619 Pts)

1. Non-randomized CAS Clinical Trials – Supportive data• CASCADE (European) Study• US FEASIBILITY Study






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• Includes a system consisting of 2 devices:

– Stent Delivery System

• Stent

• Delivery catheter

– Emboli Protection Device

CAROTID ARTERY STENTINGCAROTID ARTERY STENTING

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Cordis PRECISECordis PRECISE™™ Nitinol Stent Nitinol Stent

Stent 5.5F PRECISE™ Nitinol Stent

System

6F PRECISE™ Nitinol Stent

System

Straight Stents Diameter x Length

5, 6, 7, & 8mm x 20, 30, & 40mm

9 & 10mm x 20, 30, & 40mm

Tapered Stents Diameter x Length

6-8mm x 30mm 7-9mm x 30mm 7-10mm x 30mm

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Stent Delivery System:

–5.5F Cordis PRECISE Nitinol Stent System

–6F Cordis PRECISE Nitinol Stent System

–Usable Length: 135 cm

–Guidewire Lumen: 0.018” compatible

Cordis PRECISECordis PRECISE™™ Nitinol Stent System Nitinol Stent System

5.5F (5 – 8 mm)

6F (9 – 10 mm)5F

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CAROTID ARTERY STENT SYSTEMCAROTID ARTERY STENT SYSTEM

Polyurethane filter on a Nitinol frame

Basket Diameter: 4 - 8 mm

Oversize basket : 0.5 – 1.5 mm vs. RVD

Filter Pore Size: 100 microns

Crossing Profile: 3.5F

Wire Diameter: 0.014”

Emboli Protection: ANGIOGUARD™ XP Emboli Capture Guidewire

23

CAS SYSTEM ANIMATIONCAS SYSTEM ANIMATION

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• Non-randomized Arms: CAS and CEA



25

CLINICAL TRIALSCLINICAL TRIALS Supportive DataSupportive Data

• Purpose– Gain experience:

• Carotid stent system• Learning curve for investigators

– Refine the stent delivery system– Evaluate the advantage of adding ANGIOGUARD™

• Two Studies– CASCADE (European) Study

• CAS, non-randomized

• n=121

• 1-year follow up

– US FEASIBILITY Study

• CAS, non-randomized

• n=261

• 3-year follow up

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CASCADE STUDYCASCADE STUDY

The The CCordis Smordis Smaart Self-Expandable rt Self-Expandable SStent tent in in CaCarotid Artery rotid Artery DDiseasiseasee

27


Objective:

• To evaluate the safety and performance of the SMART Stent with or without ANGIOGUARD™

emboli capture device in patients with high grade carotid artery stenosis

• Primary Endpoint: Ipsilateral stroke or procedural related death within 30 days of stent implantation

28

CASCADE STUDYCASCADE STUDYOverviewOverview

Design:

• Multi-center, prospective, non-randomized study

• Nine centers across Europe

• 7F SMART Stent Delivery System

• 121 patients enrolled (31 with ANGIOGUARD™)

• Conducted from September 1998 until May 2002

Inclusion Criteria:• >70% stenosis if symptomatic by U/S or angiography• >85% stenosis if asymptomatic by U/S or angiography• Stenosis between origin of CCA and extracranial segment of the ICA

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0.0

7.4

0

5

10

15

20

25

Death Ipsilateral Stroke

CASCADE STUDY CASCADE STUDY 30-Day Data30-Day Data

%

n=121

30

CASCADE STUDY CASCADE STUDY 30-Day Outcomes With/Without ANGIOGUARD30-Day Outcomes With/Without ANGIOGUARD™™

2.2

6.7

8.9

0.0

3.23.2

0

5

10

15

20

25

Ipsilateral Stroke Maj Ipsi Minor Ipsi

Stent Alone (n=90)

Stent + ANGIOGUARD (n=31)

%

P=0.45

P>0.99

P=0.68

31


Conclusion:

• Carotid artery stenting was found to be feasible for the treatment of carotid stenosis

• The ANGIOGUARD™ distal protection device functioned well and reduced the risk of distal embolization, resulting in fewer strokes.

– 30-day stroke rate of 3.2%, with no major strokes

32

US FEASIBILITY STUDYUS FEASIBILITY STUDY

The Cordis Nitinol Carotid Stent and The Cordis Nitinol Carotid Stent and Delivery System (SDS) in Patients with de Delivery System (SDS) in Patients with de novo or Restenotic Native Carotid Artery novo or Restenotic Native Carotid Artery

Lesions TrialLesions Trial

33


Objective:

• Primary: Assess the feasibility of carotid artery stenting in the treatment of obstructive carotid artery disease

• Secondary: Assess and standardize optimal operator techniques for pivotal trial

34

US FEASIBILITY STUDYUS FEASIBILITY STUDYOverviewOverview

Design:

• Non-randomized, prospective, 33 center trial• 6/7F SMART™ and 5.5F PRECISE™ SDS• 261 patients enrolled

– 176 stent– 85 stent plus ANGIOGUARD™

• Sept 1998 through July 2001• Follow up to 3 years

Key Inclusion Criteria:• Symptomatic >60% stenosis by U/S or angiography• Asymptomatic >80% stenosis by U/S or angiography• Native Common or Internal Carotid Artery

35

US FEASIBILITY STUDYUS FEASIBILITY STUDYOverview - contOverview - cont

Key Inclusion Criteria: (cont)

High Risk for Surgical EndarterectomyAnatomic risk factors (not ACAS eligible):

– Restenosis after CEA

– Radical neck dissection

– Contralateral carotid artery occlusion

– Ostial lesion of the common carotid

– High take-off carotid bifurcation disease

36


Primary Endpoint:

• 30-day MAE (death, any stroke, &/or MI)

Key Secondary Endpoints:

• Major clinical events

– 6 months, 1, 2, 3 years

• Patency (< 50% restenosis) by carotid U/S

– 48 hours, 30 days, 6 months, 1, 2, & 3 years

• Neurological assessments

– 28 hours, 30 days, 6 months, 1, 2, & 3 years

37

0.8 1.1

6.1 6.9

0

5

10

15

20

25

Death MI Stroke MAE

%

US FEASIBILITY STUDYUS FEASIBILITY STUDY30-Day Events30-Day Events

n=261

38

US FEASIBILITY STUDYUS FEASIBILITY STUDY30-Day Events With/Without ANGIOGUARD30-Day Events With/Without ANGIOGUARD™™

1.1

8.0

2.3

5.1

8.5

3.52.4

0.02.4

0.00

5

10

15

20

25

Death All Stroke Major Ipsi Minor Ipsi MAE

Stent Only (n = 176)

Stent + ANGIOGUARD (n = 85)

P = 1.00P = 0.31

P= 0.51 P = 0.19% P = 0.10

39

US FEASIBILITY STUDYUS FEASIBILITY STUDY Cumulative Percentage of MAE to 1080 DaysCumulative Percentage of MAE to 1080 Days

6.9%

30

10.9%

16.8%

21.8%

Days: 30 360 720 1080

N at Risk: 247 218 177 113

Error bars are 1.5 X S.E.

Time After Initial Procedure (days)

Cu

mu

lati

ve P

erce

nta

ge

of

MA

E

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US FEASIBILITY STUDY US FEASIBILITY STUDY Cumulative Percentage of All Stroke to 30 Days and Cumulative Percentage of All Stroke to 30 Days and

Ipsilateral Stroke from 31-1080 DaysIpsilateral Stroke from 31-1080 Days

6.1%7.3%

8.7% 8.7%

30

Days: 30 360 720 1080

N at Risk: 247 218 176 113


Cu

mu

lati

ve P

erce

nta

ge

of

Str

ok

e

41

US FEASIBILITY STUDYUS FEASIBILITY STUDY Cumulative Percentage of Death to 1080 DaysCumulative Percentage of Death to 1080 Days

9.0%

13.9%

4.0%

0.8%

30

Days: 30 360 720 1080

N at Risk: 258 234 192 127


Cu

mu

lati

ve P

erce

nta

ge

of

Dea

th

42


Conclusion:

• Demonstrated feasibility of carotid stenting with the Cordis PRECISE™ Nitinol Stent System

• ANGIOGUARD™ emboli protection device reduced the incidence of stroke– 30-day stroke rate 2.4%, with no major strokes

• Provided run-in to pivotal study

43

8.0

10.08.6

2.4 3.2 2.6

0

5

10

15

20

25

FEASIBILITY CASCADE POOLEDFEASIBILITY/CASCADE

Without ANGIOGUARD

With ANGIOGUARD

CAROTID STENTCAROTID STENT30-Day Stroke Rates by Study and ANGIOGUARD30-Day Stroke Rates by Study and ANGIOGUARD™™

P=0.10 P=0.45 P=0.02%

44

CONCLUSIONS FROM SUPPORTIVE CONCLUSIONS FROM SUPPORTIVE STUDIESSTUDIES

• Refinement of CAS System– Reduction in profile (7F to 5.5F) – Improvement in design

• Data supports benefit of ANGIOGUARD™ emboli protection device in reducing stroke

• Demonstrated the feasibility of CAS

45










46

SAPPHIRE PIVOTAL STUDYSAPPHIRE PIVOTAL STUDY

Ken Ouriel, M.D., F.A.C.S, F.A.C.C.

Chairman, Division of Surgery

Chairman, Department of Vascular Surgery

Cleveland Clinic Foundation

47

SAPPHIRE STUDYSAPPHIRE STUDY

Objective:

To compare the safety and effectiveness of carotid stenting with emboli protection to endarterectomy in the treatment of carotid artery disease in high-risk patients.

48

Patients Referred for Evaluation of Carotid DiseaseScreened for SAPPHIRE Inclusion/Exclusion Criteria

2294 patients

SAPPHIRE STUDYSAPPHIRE STUDYTrial Design and Patient FlowTrial Design and Patient Flow

Evaluated by panel of physicians (interventionalist, surgeon, neurologist) who concur on qualification of patient

n = 747

49

RCT 334 Randomized (310 Treated)

StentTreatment

n=167

CEATreatment

n=167

Surgeon & Interventionalist will treat patient



n = 747

50

Non-Randomized Stent Arm

n=406


Surgeon: unacceptable risk for CEA

StentTreatment

n=167

CEATreatment

n=167




n = 747

51


n=406

Non-Randomized CEA Arm

n=7


Interventionalist: unacceptable risk

for stenting


StentTreatment

n=167

CEATreatment

n=167




n = 747

52


Primary Endpoint:

• Death (all-cause), any stroke, and MI to 30 days post-procedure plus death (all-cause) and ipsilateral stroke between days 31 and 360 post-procedure.

53

SAPPHIRE STUDYSAPPHIRE STUDYDifferences Between SAPPHIRE and Previous Surgical TrialsDifferences Between SAPPHIRE and Previous Surgical Trials

• Primary endpoint included all-cause mortality for 1 year

• MAE includes MI in addition to death/stroke• 24-hour post procedure stroke evaluation performed

by neurologist• Use of Stroke scales in addition to PEx• Objective vessel patency data obtained by

duplex U/S • Different specialties providing input on treatment

strategy (multi-disciplinary team)

54

SAPPHIRE STUDYSAPPHIRE STUDYRelevance of MI as Part of the Primary EndpointRelevance of MI as Part of the Primary Endpoint

• MI leads to disability, death, prolonged hospitalization, and increased health care costs – key safety endpoint

• In patients undergoing peripheral vascular surgery who sustain a non-Q wave MI:– 6-fold increase in mortality over 6 mo1

– Perioperative MI predicts mortality at one-year2

– 27-fold increased risk of another MI over the next 6 mo1

• Thus, perioperative MI is a strong surrogate for long-term mortality after vascular surgical procedures

• Perioperative MI is part of the primary endpoint for other CAS trials (e.g. CREST)

1Kim et al. Circulation 2002;106:2366-23712McFalls et al. Chest 1998;113:681-686

55

DEFINITIONSDEFINITIONS

Myocardial Infarction:

Q wave MI

Chest pain or other acute symptoms consistent with myocardial ischemia and new pathological Q waves in two or more contiguous ECG leads as determined by an ECG Core Laboratory or independent review by the CEC, in the absence of timely cardiac enzyme data.

Non-Q wave MI

CK ratio >2, CK-MB >1 in the absence of new, pathological Q waves.

56

DEFINITIONS – (cont)DEFINITIONS – (cont)

Stroke:

Any non-convulsive, focal neurological deficit of abrupt onset persisting more than 24 hours was a stroke. The deficit must correspond to a vascular territory. Strokes were classified as major or minor using the NIH Stroke, Rankin and Barthel scales.

For a stroke to be minor, it must be minor on all three scales. A stroke rated as major on any scale was considered major if the deficit persisted more than 3 months. Disabilities or impairments attributed to medical conditions that were non-neurological in origin were not considered strokes.

57

SAPPHIRE STUDYSAPPHIRE STUDY Statistical Analysis Plan (Randomized)Statistical Analysis Plan (Randomized)

• Primary hypothesis: Non-inferiority of CAS to CEA– Primary Endpoint: Composite 360-day MAE– 3% non-inferiority delta assumed

(i.e., Stent no more than 3% higher than CEA)– If non-inferiority demonstrated, then test for superiority (2°

hypothesis)

• Study was designed to stop enrollment based on interim analysis of 30-day MAE (2° endpoint) with final analysis on360 day data (1° endpoint)

• Enrollment stopped for administrative reasons• First planned interim analysis at 300 patients was not done as

it was already evident that enrollment would stop • Final analysis on the 1° endpoint utilized the interval censored

survival analysis method designated in protocol• No adjustments were required since no interim analysis

performed

58

SAPPHIRE STUDYSAPPHIRE STUDYDiminishing Enrollment (Randomized)Diminishing Enrollment (Randomized)

Rand enrolled

0

50

100

150

200

250

300

350

Tota

l # o

f Pat

ient

s

Rand enrolled

Competing CAS registries

Stop Enrollment

59

SAPPHIRE STUDY SAPPHIRE STUDY Key Inclusion CriteriaKey Inclusion Criteria

• Patients referred for treatment of Carotid Artery Disease

– Symptomatic >50% stenosis by U/S or angiography– Asymptomatic >80% stenosis by U/S or angiography

• Disease of Native Common or Internal Carotid Artery

• Consensus agreement by multidisciplinary team

– Interventionalist, Consulting Neurologist, Surgeon

• Must also have at least 1 co-morbid condition which increases the risk of endarterectomy:

– Anatomic– Medical

60

• Anatomic factors:–Contralateral carotid occlusion

–Contralateral laryngeal nerve palsy

–Radiation therapy to neck

–Previous CEA with recurrent stenosis

–Difficult surgical access

–Severe tandem lesions

SAPPHIRE STUDYSAPPHIRE STUDYKey Inclusion Criteria - contKey Inclusion Criteria - cont

61

• Medical Co-morbidities:– CHF (class III/IV) &/or severe LV dysfunction

(LVEF <30%)

– Open heart surgery within 6 weeks

– Recent MI (1 day to 4 weeks prior)

– Angina at low workload or unstable angina (CCS class III/IV)

– Severe pulmonary disease

– Age greater than 80 years

SAPPHIRE STUDYSAPPHIRE STUDYKey Inclusion Criteria - contKey Inclusion Criteria - cont

62


Stent Treatment

n=167

CEA Treatment

n=167




n=406


n=7


n = 747

63

SAPPHIRE STUDYSAPPHIRE STUDYDemographics – Randomized PatientsDemographics – Randomized Patients

Characteristic

Randomized Stent

Randomized CEA

P-value

Mean Age (years) 72.5 72.3 0.86

% Symptomatic 29.9% 27.7% 0.72

% Male 66.9% 67.1% 1.00

History of Hypertension 85.5% 85.1% 1.00

Diabetes Mellitus 25.3% 27.5% 0.71

History Dyslipidemia 78.5% 76.9% 0.79

Coronary Artery Disease 85.8% 75.5% 0.03

Previous CABG 43.4% 30.8% 0.02

Previous PTCA (coronary) 34.8% 23.4% 0.03

CCS III or IV 24.1% 14.7% 0.16

Previous Q or Non-Q MI 29.7% 35.3% 0.33

64

SAPPHIRE STUDY SAPPHIRE STUDY Acute Procedure & Device Outcomes*Acute Procedure & Device Outcomes*

• Stent Delivery Success**: - Randomized Stent: 99.4%- Non-Randomized Stent: 99.8%

• Device Success (Stent): <30% DS *** <50% DS

– Randomized Stent: 91.2% 99.4%– Non-Randomized Stent: 89.6% 98.5%

• ANGIOGUARD™ Success (Deployment and Retrieval)

Initial Attempt*** Ultimate Placement

– Randomized Stent: 95.6% 98.1%– Non-Rand Stent: 91.6% 95.1%

* Patients in whom treatment was attempted ** Device Failures Tables *** Per Protocol Definition

65

SAPPHIRE STUDY OUTCOMESSAPPHIRE STUDY OUTCOMES

Data Presented Are Based on Data Presented Are Based on Intent-to-Treat AnalysesIntent-to-Treat Analyses

(unless otherwise specified)(unless otherwise specified)

66


Stent Treatmentn=167

CEA Treatmentn=167


Clinical 93.5%

Ultrasound 80.6% Ultrasound 69.2%

Clinical 85.6%

1 Year Compliance

All events adjudicated by independent CEC

Angiograms and ultrasounds reviewed by independent core labs

67

2.4 3.0

6.0

9.6

1.2

3.62.4

4.8

0

5

10

15

20

25

Death Stroke MI MAE

CEA (n=167)

Stent (n=167)

SAPPHIRESAPPHIRE All Randomized Patients at 30 DaysAll Randomized Patients at 30 Days

%

P=0.68P=1.00

P=0.17

P=0.14

68

Events Stent (167 pts) CEA (167 pts) P-value

Death:

12 (7.2%)

21 (12.6%)

0.14

Stroke: 10 (6.0%) 12 (7.2%) 0.83

Major Ipsilateral 1 (0.6%) 5 (3.0%) 0.21 Minor Ipsilateral 6 (3.6%) 3 (1.8%) 0.50

MI (Q or NQ): 4 (2.4%) 10 (6.0%) 0.17 (30-day)

MAE: 20 (12.0%) 32 (19.2%) 0.10

SAPPHIRE STUDYSAPPHIRE STUDY Primary Endpoint at 360 Days Primary Endpoint at 360 Days

Randomized Patients – Overall Rates

69

SAPPHIRE STUDYSAPPHIRE STUDYPrimary Endpoint – 360-day MAEPrimary Endpoint – 360-day MAE

Non-Inferiority Statistics

-20 -15 -10 -5 0 5 10 15

Stent CEA %Difference [95% C.I.]

12.0% (20/167) 19.2% (32/167)

–7.2%[–14.9%, 0.6%]

Margin of Non-inferiority

Stent Non-inferior to CEA

3%

% Difference (Stent – CEA)

70

SAPPHIRE STUDYSAPPHIRE STUDY Primary Endpoint at 360 DaysPrimary Endpoint at 360 Days

12.6

7.26.0

19.2

7.2

12.0

2.4

6.0

0

5

10

15

20

25

Death Stroke MI MAE

CEA (n=167)Stent (n=167)

P=0.14

P=0.83P=0.17

P=0.10

(30 day)

%

71

SAPPHIRE STUDYSAPPHIRE STUDY Primary Endpoint at 360 DaysPrimary Endpoint at 360 Days

7.2

3.01.8

3.6

6.0

0.60

5

10

15

20

25

Stroke Major Ipsi Minor Ipsi

CEA (n=167)

Stent (n=167)

%

P=0.21 P=0.50

P=0.83

72

SAPPHIRE STUDYSAPPHIRE STUDYCumulative % of MAE to 360 DaysCumulative % of MAE to 360 Days

Randomized Patients – Kaplan Meier AnalysisRandomized Patients – Kaplan Meier Analysis

CEA 20.1%

Stent 12.2%

LR p = 0.053

9.8%

4.8%


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9.8%

4.8%

30

12.2%

20.1%

Days: 30 360 720

N at Risk (CEA): 161 125 59

N at Risk (Stent): 163 147 88

CEA 26.7%

Stent 19.2%


Randomized Patients – Kaplan Meier AnalysisRandomized Patients – Kaplan Meier Analysis

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9.8%

4.8%

12.2%

20.1%

CEA 26.7%

Stent 19.2%

74

Days: 30 360 720

N at Risk (CEA): 159 130 59


3.6% Stent3.1% CEA

30

5.8% CEA 5.8% CEA5.9% Stent4.9% Stent

* All Stroke to 30 days and ipsilateral stroke from 31-720 Days

SAPPHIRE STUDYSAPPHIRE STUDYCumulative % of Stroke* to 720 DaysCumulative % of Stroke* to 720 Days

Randomized Patients - Kaplan Meier AnalysisRandomized Patients - Kaplan Meier Analysis

Time After Initial Procedure (days)Cu

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75

1.2% Stent

2.5% CEA

30

7.4% Stent

13.5% CEA

20.9% CEA

14.4% Stent

Days: 30 360 720

N at Risk (CEA): 162 137 64


SAPPHIRE STUDYSAPPHIRE STUDYCumulative % of Death to 720 DaysCumulative % of Death to 720 Days

Randomized Patients - Kaplan Meier AnalysisRandomized Patients - Kaplan Meier Analysis


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• Total Deaths: 33– CEA: 21– Stent: 12

• Total Number of Neurologic Deaths: 4 – CEA: 3– Stent: 1

• Non-Neurologic Deaths 29

SAPPHIRE STUDYSAPPHIRE STUDYCause of Death at 360 Days - RCause of Death at 360 Days - Randomizedandomized

77

• Total Deaths: 33– CEA: 21– Stent: 12

• Total Number of Neurologic Deaths: 4 – CEA: 3– Stent: 1

• Non-Neurologic Deaths CEA Stent

29 18 11– Cardiac 18 10 8 – Respiratory Failure 4 3 1– Cancer 3 1 2– Renal Failure 1 1 0– Multi-system Failure 3 3 0

SAPPHIRE STUDYSAPPHIRE STUDYCause of Death at 360 Days - RandomizedCause of Death at 360 Days - Randomized

78

SAPPHIRE STUDYSAPPHIRE STUDYComplicationsComplications

Stent (n=167)

CEA

(n=167)

P-value

Target Lesion Revascularization (TLR)

1 (0.6%) 6 (3.6%) 0.12

Vessel Thrombosis 0 (0.0%) 0 (0.0%) ---

Major Bleeding 15 (9.0%) 17 (10.2%) 0.85

Cranial Nerve Injury 0 (0.0%) 8 (4.8%) 0.01

79

SAPPHIRE STUDYSAPPHIRE STUDYRestenosis Rates and TLR at 360 DaysRestenosis Rates and TLR at 360 Days

In-Vessel Restenosis by U/S Stent

(n=167)

CEA

(n=167)

P-value

>50% Diameter Stenosis* 19.7% (24/122) 31.3% (30/96) 0.06

>70% Diameter Stenosis 0.8% (1/122) 5.2% (5/96) 0.09

>80% Diameter Stenosis 0.8% (1/122) 4.2% (4/96) 0.17

TLR – Clinically driven

(to 360 days)

0.6% (1/167) 3.6% (6/167) 0.12

* Protocol Definition

80


Analysis of the Evaluable Analysis of the Evaluable (Treated) Patients(Treated) Patients

81

SAPPHIRE STUDYSAPPHIRE STUDYRandomized Patients Who Were Not TreatedRandomized Patients Who Were Not Treated

Stent CEA

Subsequent to randomization found to not meet Inclusion Criteria:

2 4

Patient Withdrew Consent: 3 8

Patient Condition Deteriorated/Too High a Risk: 3 2

Other: 0 2

TOTAL: 8 16

82

Events Stent (159 pts) CEA (151 pts) P-value

Death:

11 (6.9%)

19 (12.6%)

0.12

Stroke: 9 (5.7%) 11 (7.3%) 0.65

Major Ipsilateral 0 (0.0%) 5 (3.3%) 0.03* Minor Ipsilateral 6 (3.8%) 3 (2.0%) 0.50

MI (Q or NQ): 4 (2.5%) 12 (7.9%) 0.04*

MAE: 19 (11.9%) 30 (19.9%) 0.06

* Significant

SAPPHIRE STUDYSAPPHIRE STUDY Primary Endpoint 360 Days – Randomized Primary Endpoint 360 Days – Randomized TREATEDTREATED Patients Patients

83


Randomized Randomized TREATEDTREATED Patients – Kaplan Meier Analysis Patients – Kaplan Meier Analysis


LR p = 0.048

CAS: 12.0%

CEA: 20.1%

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n=406


n=7RCT

334 Randomized (310 Treated)

StentTreatment

n=167

CEATreatment

n=167





n = 747

85

SAPPHIRE STUDYSAPPHIRE STUDYNon-Randomized Stent Arm vs. CEA Randomized Non-Randomized Stent Arm vs. CEA Randomized

Demographic CharacteristicsDemographic Characteristics


CEA Randomized

P-value

Mean Age 71.4 72.3 0.30

% Male 64.3% 67.1% 0.56

CCS III or IV

31.5% 14.7% 0.01

Previous Radiation Therapy

16.2% 5.7% <0.01

High Cervical ICA Lesion 12.7% 4.4% <0.01

Prior CEA 45.2% 26.7% <0.01

History Stroke 32.3% 23.8% 0.05

86

SAPPHIRE STUDYSAPPHIRE STUDYMAE at 360 DaysMAE at 360 Days

Rand CEA: 20.1%

Non-Rand Stent: 16.0%

Rand Stent: 12.2%

Non-Randomized Stent Arm vs. Randomized Stent & CEA


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Rand CEA: 9.8%

Non-Rand Stent: 6.9%

Rand Stent: 4.8%

87

• Original non-inferiority analysis based on OPC ~12-14% plus 4% delta

– Weighted OPC calculated at 12.94 was not met – OPC estimated (1999) without benefit of multi-center randomized data from high-surgical risk studies

• SAPPHIRE CEA arm– 1 year MAE rate of 19.2%

– Has frequency of high surgical-risk characteristics

•Agency consulted in March 2003

– FDA suggested supplemental non-inferiority analysis

• Non-Randomized Stent Arm to the Randomized CEA Arm

• Adjustment for differences in baseline demographics

SAPPHIRE STUDYSAPPHIRE STUDYNon-Randomized Stent Arm Non-Randomized Stent Arm

88

-20 -15 -10 -5 0 5 10 15

%Difference[95% C.I.]

–5.3%[–13.4%, 3.0%]

Margin of Non-inferiority

% Difference (Non-randomized Stent – Randomized CEA)

Stent Non-inferior to CEA

3%

Non-Inferiority Statistics

SAPPHIRE STUDYSAPPHIRE STUDYPrimary Endpoint – 360-day MAE Adjusted for Baseline CharacteristicsPrimary Endpoint – 360-day MAE Adjusted for Baseline Characteristics

89

SAPPHIRE STUDYSAPPHIRE STUDYComplicationsComplications

Randomized Stent

(n = 167)

Randomized CEA

(n = 167)

Non-RandStent

(n = 406)

P-value

(CEA vs. Non-Rand)

TLR 1 (0.6%) 6 (3.6%) 3 (0.7%) 0.02

Vessel Thrombosis

0 (0.0%) 0 (0.0%) 3 (0.7%) 0.56

Major Bleeding

15 (9.0%) 17 (10.2%) 54 (13.3%) 0.33

Cranial Nerve Injury

0 (0.0%) 8 (4.8%) 0 (0.0%) <0.01

90


n=406


n=7RCT

334 Randomized (310 Treated)

StentTreatment

n=167

CEATreatment

n=167



Interventionalist: unacceptable risk

for stenting



n = 747

91

• Study is not powered for subgroup analyses

• Symptomatic/Asymptomatic:

– Randomization stratified by +/- symptoms

– Subgroup analyses pre-specified

• Subgroup sample sizes

– Symptomatic Patients: 96

– Asymptomatic Patients: 237

SAPPHIRE STUDYSAPPHIRE STUDY Subgroup AnalysesSubgroup Analyses

92

SAPPHIRE STUDYSAPPHIRE STUDY30-Day MAE Asymptomatic (ITT)30-Day MAE Asymptomatic (ITT)

0.8

3.3

6.7

9.2

1.7

5.1

2.6

6.0

0

5

10

15

20

25

Death Stroke MI MAE

CEA (n=120)

Stent (n=117)

%

P=0.62

P=0.54P=0.22

P=0.46

93

10.8

7.58.3

19.2

5.1

7.7

2.6

10.3

0

5

10

15

20

25

Death Stroke MI MAE

CEA (n=120)

Stent (n=117)

SAPPHIRE STUDYSAPPHIRE STUDY360-Day MAE Asymptomatic (ITT) 360-Day MAE Asymptomatic (ITT)

%P=0.15

P=1.00 P=0.08

P=0.07

94

SAPPHIRE STUDYSAPPHIRE STUDYCumulative % of MAE Asymptomatic to 360 DaysCumulative % of MAE Asymptomatic to 360 DaysAll Randomized Patients – Kaplan Meier AnalysisAll Randomized Patients – Kaplan Meier Analysis


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LR p = 0.04

CEA: 20.3%

Stent: 10.5%

95

6.5

2.2

4.3

10.9

0.0 0.0

2.0 2.0

0

5

10

15

20

25

Death Stroke MI MAE

CEA (n=46)

Stent (n=50)

SAPPHIRE STUDYSAPPHIRE STUDY30-Day MAE Symptomatic (ITT)30-Day MAE Symptomatic (ITT)

P=0.10

P=0.61P=0.48

P=0.11

%

96

17.4

6.5

4.3

12.0

2.0

4.0

0

5

10

15

20

25

Death Stroke MI

CEA (n=46)

Stent (n=50)

SAPPHIRE STUDYSAPPHIRE STUDY360-Day MAE Symptomatic (ITT)360-Day MAE Symptomatic (ITT)

%

P=0.57

P=0.35P=1.00

97

SAPPHIRE STUDYSAPPHIRE STUDYCumulative % of MAE Symptomatic to 360 DaysCumulative % of MAE Symptomatic to 360 Days

All Randomized Patients – Kaplan Meier AnalysisAll Randomized Patients – Kaplan Meier Analysis


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LR p = 0.58

CEA: 20.0%

Stent: 16.3%

98

19.619.2

15.7

10.3

16.116.0

0

5

10

15

20

25

Randomized Stent Non-RandomizedStent

CEA

Asymptomatic

Symptomatic

%

P=0.07

SAPPHIRE STUDYSAPPHIRE STUDY360-Day MAE Symptomatic vs. Asymptomatic (ITT)360-Day MAE Symptomatic vs. Asymptomatic (ITT)

n=281 n=46n=124 n=120n=117 n=50

99

9.9

15.7

21.3

16.7 16.1 16.3

0

5

10

15

20

25

Randomized Stent Non-Randomized Stent CEA

Asymptomatic

Symptomatic

SAPPHIRE STUDYSAPPHIRE STUDY360-Day MAE Symptomatic vs. Asymptomatic Treated (Evaluable) Patients360-Day MAE Symptomatic vs. Asymptomatic Treated (Evaluable) Patients

P=0.02

%

n=281 n=124n=111 n=48 n=108 n=43

100

SAPPHIRE STUDYSAPPHIRE STUDYSurgeon Experience and OutcomesSurgeon Experience and Outcomes

• Experience and outcomes for surgeons in SAPPHIRE trial are consistent with previous surgical data

– CEA volume– Outcomes– Complication rates

101

Pre-study survey conducted

• 53 SAPPHIRE surgeons

– Mean of 36.3 procedures per year

– Median of 28 procedures per year

SAPPHIRE STUDYSAPPHIRE STUDYSurgeon Experience & JudgmentSurgeon Experience & Judgment

102

CEA OUTCOMES BY VOLUMECEA OUTCOMES BY VOLUME

0

0.5

1

1.5

2

2.5

3

1-6 7-21 >21

Mortality (%)Wennberg, JAMA 289: 1278-1281, 1998

Annualized Volume Tercile - # Procedures in Medicare Treated Patients

Tercile of cases per year – all CEA surgeons

Mo

rta

lity

(%)

103

CEA OUTCOMES BY VOLUMECEA OUTCOMES BY VOLUME

0

0.5

1

1.5

2

2.5

3

1-6 7-21 >21

Mortality (%)Wennberg, JAMA 289: 1278-1281, 1998

Annualized Volume Tercile - # Procedures in Medicare Treated Patients

Tercile of cases per year – all CEA surgeons

Mo

rta

lity

(%)

SAPPHIRE 1 4 48 Cases/Surgeon

104

CRANIAL NERVE INJURYCRANIAL NERVE INJURYComparison with Other StudiesComparison with Other Studies

SAPPHIRE Randomized CEA: 4.8%

NASCET: 7.2%

VA Cooperative Study: 3.8%

ACAS: NA

NASCET AND VA STUDY EXCLUDED REPEAT CEA

105

30-Day Ipsilateral Stroke

SURGICAL OUTCOMES vs. OTHER TRIALSSURGICAL OUTCOMES vs. OTHER TRIALS

Error Bar = 95% CIError Bar = 95% CI%

1.8%2.5%

5.5%

0.0%

1.8%

0%

2%

4%

6%

8%

10%

SAPPHIRE SAPPHIRESYMP

NASCET SAPPHIREASYMP

ACAS

106

Comparison of 30-day ipsilateral stroke rates

• SAPPHIRE randomized and non-randomized symptomatic stent patients vs. NASCET

• SAPPHIRE randomized and non-randomized asymptomatic stent patients vs. ACAS

CAS OUTCOMES TO OTHER SURGICAL TRIALSCAS OUTCOMES TO OTHER SURGICAL TRIALS

107

6.5%5.5%

0.0%0%

2%

4%

6%

8%

10%

12%

14%

SAPPHIRE SYMP Rand SAPPHIRE SYMP Non-Rand

NASCET


CAS OUTCOMES TO OTHER SURGICAL TRIALSCAS OUTCOMES TO OTHER SURGICAL TRIALSSymptomatic PatientsSymptomatic Patients

Error Bar = 95% CIError Bar = 95% CI

%

108

1.8%

3.2%

4.3%

0%

2%

4%

6%

8%

10%

SAPPHIRE ASYMPRand

SAPPHIRE ASYMPNon-Rand

ACAS


CAS OUTCOMES TO OTHER SURGICAL TRIALSCAS OUTCOMES TO OTHER SURGICAL TRIALSAsymptomatic PatientsAsymptomatic Patients

Error Bar = 95% CIError Bar = 95% CI%

109

SAPPHIRE STUDYSAPPHIRE STUDYCAS 30-Day MortalityCAS 30-Day Mortality

• CAS 30-day all cause mortality– Symptomatic

• Randomized – 0.0%• Non-randomized – 0.8%

– Asymptomatic• Randomized – 1.7%• Non-randomized – 2.8%

110


ConclusionsConclusions

111

SAPPHIRE STUDYSAPPHIRE STUDYConclusions: Randomized ArmConclusions: Randomized Arm

• The primary endpoint of the study was achieved demonstrating CAS is non-inferior to CEA

• Trends favoring CAS over CEA– Major Ipsilateral stroke

– MI

– TLR

– Restenosis (>50% DS)

• Significant decrease in cranial nerve injuries

112

SAPPHIRE STUDY SAPPHIRE STUDY Conclusions: Randomized ArmConclusions: Randomized Arm

• Symptomatic and asymptomatic subgroups

– ITT Asymptomatic: Significant improvement at 360 days in favor of CAS compared to CEA with 50% reduction in MAE rate

– ITT Symptomatic: MAE rates at 360 days were similar between CAS and CEA

– Outcomes for ipsilateral stroke overlap those from NASCET and ACAS

113

• Risk factors contributing to “too high risk for CEA”:– Anatomic

• Prior CEA• Prior radiation therapy• High cervical ICA lesion

– Medical • Angina Class CCS III or IV• Previous stroke

– Non-inferior to randomized CEA

• Surgeons in SAPPHIRE were experienced in CEA and had outcomes similar to referenced literature

• Too high risk for surgery Too high risk for stenting– True for symptomatic and asymptomatic patients

SAPPHIRE STUDYSAPPHIRE STUDYConclusions: Non-Randomized Stent ArmConclusions: Non-Randomized Stent Arm

114

AGENDAAGENDA

• Project Overview & CAS Background









115

PROFESSIONAL EDUCATIONPROFESSIONAL EDUCATION

Carotid Artery Stent Education Carotid Artery Stent Education SystemSystem

116

CAROTID ARTERY STENT CAROTID ARTERY STENT TRAINING SYSTEMTRAINING SYSTEM

• Training system is intended to build upon already existing endovascular expertise to develop a physicians knowledge and technical expertise in performing CAS

• System was developed using a variety of consultants:

– SAPPHIRE Investigators

– Internet based training

– Simulator modeling

– Proficiency measurements

117

On-line On-line DidacticDidactic

On-line On-line DidacticDidactic ObservationObservation ObservationObservation SimulationSimulationSimulationSimulation Staff Staff

In-ServiceIn-Service

Staff Staff In-ServiceIn-Service

Proctor Proctor NetworkNetwork

Proctor Proctor NetworkNetwork

Step 1 Step 2 Step 3 Step 4 Step 5

InternetInternetDeliveryDelivery

InternetInternetDeliveryDelivery

Regional Education Regional Education CenterCenter

Regional Education Regional Education CenterCenter

On-site Training at On-site Training at Physician’s FacilityPhysician’s Facility

On-site Training at On-site Training at Physician’s FacilityPhysician’s Facility

PatientPatientOutcomesOutcomes

PatientPatientOutcomesOutcomes

Staff Staff TrainingTraining

Staff Staff TrainingTraining

DELIVERY PROCESSDELIVERY PROCESS

Proficiency Measurement

118

On-line didactic training: Transferring Expert Knowledge

Through doing and decision making Goal

Assure Procedural Success Detailed understanding of anatomy Appropriate case selection High performance technical execution

Training at Regional Education Center: Small group setting – review 4 Modules Over 2 Days

Didactic Review, Case Observation, Simulation Lab, Product Lab

Physicians interact with realistic graphical simulations assess task performance demonstrate understanding of the learning objectives


119

• On-site training at physician’s facility by physician proctors:– Network of CAS experienced physician proctors– Proctor Sign Off or Additional Training

Recommendations Based on Proficiency Standards

• Training Program:– 34 Hours of Training with exposure to a minimum of

15 Cases – Serves as the foundation for hospital credentialing


120

INITIAL ASSESSMENT OF TRAINING INITIAL ASSESSMENT OF TRAINING Institutional IDEsInstitutional IDEs

• 36 centers (30 non-Sapphire Investigators)

• All investigators were trained and proctored on use of the stent and the emboli protection system

• Patient selection criteria similar to the US FEASIBILITY Study

• Neurologist evaluation 24 hours and 30 days post-procedure

• Data are site reported and unadjudicated

121

0.62.6

1.4

4.3

0

5

10

15

20

25

Death Stroke MI MAE

%

INSTITUTIONAL IDEs INSTITUTIONAL IDEs 30-Day Events - Site Reported30-Day Events - Site Reported

122

COMPARISON OF 30-DAY EVENT RATESCOMPARISON OF 30-DAY EVENT RATESTreatedTreated Patients with ANGIOGUARDPatients with ANGIOGUARD™™ Only Only

0.6

3.2

0.02.4

0.03.1

0.62.6

0

5

10

15

20

25

Stroke Death

Cascade (n=31)Feasibility (n=85)Sapphire (n=159)Site IDE (n=491)

%

123

Carotid Stenting With Emboli Protection For The Treatment of

Obstructive Carotid Artery Disease

POST-MARKETING SURVEILLANCEPOST-MARKETING SURVEILLANCE

124


Objective:

• To compare clinical outcomes with historical control data from SAPPHIRE in the early time period following approval and assess the effectiveness of the training program

Design:

• Multicenter, prospective, non-randomized, open label

Primary Endpoint:

• 30-day composite of major adverse clinical events(MAE = all death and all stroke)

125

Study Population:• High Risk patients with de novo or restenotic lesions• > 1000 patients• Inclusion Criteria: Per Label Indications

Follow-up:• Neurologic examinations at discharge and 30 days (Neurologist)• Clinical events tracking through discharge

– 30-day office visit– 9-month telephone contact

Monitoring with built in stopping rule:• Electronic data capture to expedite review of outcomes


126

CAROTID ARTERY STENTING CAROTID ARTERY STENTING WITH EMBOLI PROTECTIONWITH EMBOLI PROTECTION

Summary and Conclusions

127

SUMMARY AND CONCLUSIONSSUMMARY AND CONCLUSIONS

• Stroke– Significant morbidity and mortality– Due to carotid disease in up to 30% of patients– Goal of Tx: to prevent stroke and improve quality of life

• CEA is the standard of care in:– NASCET/ACAS eligible and ineligible patients– Symptomatic and asymptomatic patients– Low, intermediate, and high risk

• There are no multi-center randomized studies that define outcomes in high medical- or surgical-risk patients

• SAPPHIRE is an objective comparison of CEA, the current interventional standard of care, with CAS, a less invasive approach to therapy

128

Cordis is seeking the following indication: • The Cordis [Carotid Stent System is] indicated for use in the treatment

of carotid artery disease in high-risk patients. High-risk is defined as patients with neurological symptoms (one or more TIA’s or one or more completed strokes) and >50% atherosclerotic stenosis of the common or internal carotid artery by ultrasound or angiogram;

and • Patients without neurological symptoms and >80% atherosclerotic

stenosis of the common or internal carotid artery by ultrasound or angiogram.

• Symptomatic and asymptomatic patients must also have one or more

condition(s) that place them at high-risk for carotid endarterectomy.


129

• This indication is supported by:• SAPPHIRE

– Achieved primary endpoint of non-inferiority of CAS to CEA for MAE at 1-year

– CAS - improved outcomes for MI and re-interventions with a significant decrease in cranial nerve injuries

• SUPPORTIVE STUDIES– CAS treatment demonstrated sustained benefit through

3-year follow up

CONCLUSIONCONCLUSION

130

• Cordis will institute a training program to ensure outcomes of carotid stenting in non-trial setting replicates safety and effectiveness demonstrated in SAPPHIRE

• Cordis will conduct a post-marketing surveillance study with the goal of– quantifying patient outcomes – confirming the adequacy of physician training


131

THANK YOUTHANK YOU

1 carotid artery stenting with emboli protection pma # p030047 cordis presentation sidney a. cohen,...

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