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CAROTID ARTERY STENTING WITH EMBOLI PROTECTION

CAROTID ARTERY STENTING WITH EMBOLI PROTECTION. PMA # P030047. Cordis Presentation Sidney A. Cohen, M.D., Ph.D. Group Director, Clinical Research. REQUESTED INDICATION .

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CAROTID ARTERY STENTING WITH EMBOLI PROTECTION

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  1. CAROTID ARTERY STENTING WITH EMBOLI PROTECTION PMA # P030047 Cordis Presentation Sidney A. Cohen, M.D., Ph.D. Group Director, Clinical Research

  2. 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. AGENDA • 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 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. BACKGROUNDStroke & 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. BACKGROUNDCarotid 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. BACKGROUND Carotid Endarterectomy - cont • Randomized clinical studies • Superiority of CEA vs. best medical therapy • NASCET1 • Symptomatic >50% diameter stenosis • ACAS2 • Asymptomatic >60% diameter stenosis • ECST3 • Symptomatic >50% diameter stenosis • VA Cooperative Study4 • Symptomatic >50% diameter stenosis • “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 TREATED WITH CEA CEA treatment of patients clearly extends beyond NASCET/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 • 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. 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 NASCET/ACAS EXCLUSION CRITERIA

  10. CEA MORTALITY 113,000 Medicare Patients (1992-1993) 30-Day Follow up Mortality % Wennberg, et al., JAMA, 279: 1278-1281, 1998

  11. PUBLISHED 30-DAY CEA EVENT RATES 1 2 3 3 % 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

  12. IN-HOSPITAL CEA OUTCOMES US ACADEMIC CENTERS • Retrospective analysis • 1160 patients • 12 academic centers in US • 1988-90 • In-hospital Death + MI +Stroke Death + MI + Stroke McCrory DC et al. Stroke 1993;24:1285-1291

  13. IN-HOSPITAL CEA OUTCOMES US ACADEMIC CENTERS Death + MI + Stroke McCrory DC et al. Stroke 1993;24:1285-1291

  14. PERCENT ASYMTOMATIC PATIENTS UNDERGOING CEA IS UP TO 75% 1 2 3 4 % 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

  15. INCIDENCE OF STROKE AT 360-DAYS 6 Asymptomatic Patients 5 4 3 Stroke Incidence (%) 2 1 0 0-19% 20-29% 30-39% 40-49% 50-59% 60-69% 70-79% 80-89% 90-99% Carotid Artery Stenosis Chambers New England Journal of Medicine. 315(14):860-5, 1986 Norris Stroke. 22(12):1485-90, 1991 Mendelsohn & Yadav, Management of Atherosclerotic Carotid Disease, Remedica Publishing, 2000

  16. TYPE OF PATIENTS CURRENTLY TREATED WITH CEA • 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

  17. RATIONALE FOR TREATMENT OF “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. AGENDA • 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

  19. CAROTID ARTERY STENTING • Includes a system consisting of 2 devices: • Stent Delivery System • Stent • Delivery catheter • Emboli Protection Device

  20. Cordis PRECISE™ Nitinol Stent

  21. Cordis PRECISE™ Nitinol Stent System • 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 5.5F (5 – 8 mm) 6F (9 – 10 mm) 5F

  22. CAROTID ARTERY STENT SYSTEM Emboli Protection:ANGIOGUARD™ XP Emboli Capture Guidewire 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”

  23. CAS SYSTEM ANIMATION

  24. AGENDA • 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

  25. CLINICAL TRIALSSupportive 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

  26. CASCADE STUDY The Cordis Smart Self-Expandable Stent in Carotid Artery Disease

  27. CASCADE STUDY • 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 STUDYOverview • 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

  29. CASCADE STUDY 30-Day Data n=121 %

  30. CASCADE STUDY 30-Day Outcomes With/Without ANGIOGUARD™ P=0.45 P=0.68 % P>0.99

  31. CASCADE STUDY 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 STUDYThe Cordis Nitinol Carotid Stent and Delivery System (SDS) in Patients with de novo or Restenotic Native Carotid Artery Lesions Trial

  33. US FEASIBILITY STUDY 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 STUDYOverview 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 STUDYOverview - cont • Key Inclusion Criteria: (cont) • High Risk for Surgical Endarterectomy • Anatomic 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. US FEASIBILITY STUDY • 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. US FEASIBILITY STUDY30-Day Events n=261 %

  38. US FEASIBILITY STUDY30-Day Events With/Without ANGIOGUARD™ P = 0.19 P= 0.51 % P = 0.10 P = 0.31 P = 1.00

  39. Days: 30 360 720 1080 US FEASIBILITY STUDYCumulative Percentage of MAE to 1080 Days N at Risk: 247 218 177 113 21.8% 16.8% 10.9% Cumulative Percentage of MAE 6.9% Error bars are 1.5 X S.E. 30 Time After Initial Procedure (days)

  40. Days: 30 360 720 1080 US FEASIBILITY STUDY Cumulative Percentage of All Stroke to 30 Days and Ipsilateral Stroke from 31-1080 Days N at Risk: 247 218 176 113 8.7% 8.7% Cumulative Percentage of Stroke 7.3% 6.1% 30 Time After Initial Procedure (days)

  41. Days: 30 360 720 1080 US FEASIBILITY STUDYCumulative Percentage of Death to 1080 Days N at Risk: 258 234 192 127 13.9% 9.0% Cumulative Percentage of Death 4.0% 0.8% 30 Time After Initial Procedure (days)

  42. US FEASIBILITY STUDY 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. CAROTID STENT30-Day Stroke Rates by Study and ANGIOGUARD™ % P=0.10 P=0.45 P=0.02

  44. CONCLUSIONS FROM SUPPORTIVE STUDIES • 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. AGENDA • 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

  46. SAPPHIRE 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 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. SAPPHIRE STUDYTrial Design and Patient Flow Patients Referred for Evaluation of Carotid Disease Screened for SAPPHIRE Inclusion/Exclusion Criteria 2294 patients Evaluated by panel of physicians (interventionalist, surgeon, neurologist) who concur on qualification of patient n = 747

  49. SAPPHIRE STUDYTrial Design and Patient Flow Evaluated by panel of physicians (interventionalist, surgeon, neurologist) who concur on qualification of patient n = 747 Surgeon & Interventionalist will treat patient RCT 334 Randomized (310 Treated) Stent Treatment n=167 CEA Treatment n=167

  50. SAPPHIRE STUDYTrial Design and Patient Flow Evaluated by panel of physicians (interventionalist, surgeon, neurologist) who concur on qualification of patient n = 747 Surgeon: unacceptable risk for CEA Surgeon & Interventionalist will treat patient Non-Randomized Stent Arm n=406 RCT 334 Randomized (310 Treated) Stent Treatment n=167 CEA Treatment n=167

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