1. Carotid Stenting Review Renan Uflacker, MD Interventional Radiology Medical University of South Carolina

2. Carotid Stent IMPORTANCEOF CAROTID ARTERY DISEASE TREATMENT

3. Stroke: 3 rd cause of death in US 3 rd cause of death in US 500,000 cases/year 500,000 cases/year 2 milion/year handicaped people 2 milion/year handicaped people HIGH SOCIAL / ECONOMIC COST Mellière et al. J Mal Vasc, 1993 Carotid Stent

4. 20 - 30% of VCA are related to carotid occlusive disease 20 - 30% of VCA are related to carotid occlusive disease Increased incidence with age (33% 50 yrs) Increased incidence with age (33% 50 yrs) De Bakey et al. J Endovasc Surg, 1996

5. Carotid Stent Stenoses > 75% Stenoses > 75% risk of stroke in 1 st yr = 2-5% Roederer et al. Stroke, 1984 Roederer et al. Stroke, 1984 Hennereci et al. Brain, 1987 Hennereci et al. Brain, 1987 Ulceration = Iminent stroke Ulceration = Iminent stroke risk of stroke = 7,5% Autret et al. Lancet, 1987 Autret et al. Lancet, 1987

6. Carotid Stent Carotid stenosis + TIA Carotid stenosis + TIA Risk of stroke in 1 st yr = 12-13% 5 th yr = 30- 37% Risk of stroke in 1 st yr = 12-13% 5 th yr = 30- 37% Sundt et al., 1987 Sundt et al., 1987 Dennis et al. Stroke, 1990 Dennis et al. Stroke, 1990 CVA - risk in 1 st yr = 59% CVA - risk in 1 st yr = 59% 5 th yr = 25-45% 5 th yr = 25-45% Sacco et al. Stroke, 1982 Sacco et al. Stroke, 1982 Meissner et al. Stroke, 1988 Meissner et al. Stroke, 1988

7. Carotid Stent Heterogeneous and ulcerated lesions = Risk 2-4 x Heterogeneous and ulcerated lesions = Risk 2-4 x Langsfeld et al. J Vasc Surg, 1989 Langsfeld et al. J Vasc Surg, 1989 Sterpetti et al. Stroke, 1988 Sterpetti et al. Stroke, 1988

8. Carotid Stent SURGICAL TREATMENT

9. Carotid Stent ENDARTERECTOMY (1953) – risk of stroke –TIA = 1-2% / Yr –CVA = 2-3% / Yr

10. Carotid Stent Clinical Trials such as NASCET/ACAS established the patern of eficacy of surgical treatment in comparison to clinical treatment Clinical Trials such as NASCET/ACAS established the patern of eficacy of surgical treatment in comparison to clinical treatment Demonstrated the superiority of the method with defined statistical criteria Demonstrated the superiority of the method with defined statistical criteria Surgery is the ¨gold standard¨ for low risk pacients Surgery is the ¨gold standard¨ for low risk pacients

11. Carotid Stent 559 symptomatic patients / 2 anos 559 symptomatic patients / 2 anos Estenoses > 70% Estenoses > 70% Risk of CVA Risk of CVA Clinical treatment = 13,1% Clinical treatment = 13,1% Surgical treatment = 2,5% Surgical treatment = 2,5% P < 0,001 P < 0,001 N Engl J Med 1991;325:445 NASCET (North American Symptomatic Carotid Trial)

12. Carotid Stent NASCET (North American Symptomatic Carotid Trial) N Engl J Med 1991;325:445 Risk CVA/peri-operatory death = 5,8% Benefits of surgery evident after 3 months Benefits for lesions > 50%

13. Carotid Stent 778 symptomatic patients / 3 yrs 778 symptomatic patients / 3 yrs stenoses > 70% stenoses > 70% Risk of CVA Risk of CVA Clinical treatment = 16,8% Surgical treatment = 2,8% p < 0,001 p < 0,001 Risk CVA/peri-operatory deaths =7,5 % Risk CVA/peri-operatory deaths =7,5 % ECST (European Carotid Surgery Trials) Lancet 1991;337:1235

14. Carotid Stent 1662 asymptomatic patients / 5 yrs 1662 asymptomatic patients / 5 yrs stenoses > 60% stenoses > 60% Risks of CVA Risks of CVA Clinical treatment =10,6% Clinical treatment =10,6% Surgical treatment = 4,8% Surgical treatment = 4,8% P < 0,004 Risk CVA/peri-operatory death = 2,3 % Risk CVA/peri-operatory death = 2,3 % Stroke 1994; 25: 2523-2524 ACAS (Asymptomatic Carotid Atherosclerosis Study)

15. Carotid Stent AHA Quality Standards Surgical Treatment CVA / Death Symptomatic Patients < 6% Symptomatic Patients < 6% Asymptomatic Patients < 3% Asymptomatic Patients < 3%

16. Carotid Stent NASCET (North American Syntomatic Carotid Trial) Cranial Nerve Lesion : 7,6% Hematoma : 5,5% Extensive list of exclusion criteria ! N Engl J Med 1991;325:445

17. Carotid Stent age > 79 anos age > 79 anos co-morbidity (cardiac/renal/hepatic/ca) co-morbidity (cardiac/renal/hepatic/ca) valvulophaty / arrithmias valvulophaty / arrithmias previous endarterectomy previous endarterectomy unstable angina / recent MI unstable angina / recent MI previous surgery (30 days) previous surgery (30 days) Exclusion Criteria - NASCET / ACAS

18. Carotid Stent Death incidence in patients treated with surgery followed by Medicare is higher in institutions participating in the NASCET/ACAS Death incidence in patients treated with surgery followed by Medicare is higher in institutions participating in the NASCET/ACAS NASCET0,6% ACAS0,1% 1,4% MEDICARE Variation in carotid endarterectomy mortality in the Medicare population: trial hospitals, volume and patient characteristics Wennberg DE, Lucas FL, Birkmeyer JD et al. JAMA 1998;279:1278

19. Carotid Stent Patients with high risk of stroke present also with high risk for surgical treatment Patients with high risk of stroke present also with high risk for surgical treatment Brown et al. J Vasc Surg, 2003; 37:32 Gasparis et al. J Vasc Surg 2003; 37:40 High risk patients Endovascular Treatment

20. Carotid Stent ENDOVASCULARTREATMENT

22. Carotid angioplasty is performed with incidence of CVA/death Carotid angioplasty is performed with incidence of CVA/death ranging 5,3-8,2%. ranging 5,3-8,2%. Diethrich et al. J Endovasc Surg,1996 Bergeron et al. Cardiovasc Surg,1996 Yadav et al. Circulation,1997 Henry et al. J Endovasc Surg,1997

23. Carotid Stent LEARNING CURVE: CLINICAL EXPERIENCE: 89/99 10 years N = 924(independent neurologic evaluation) #Angioplasties Complications #Angioplasties Complications 89/91 1118,8% 89/91 1118,8% 92/94 1964,8% 92/94 1964,8% 95/99 6172,0% 95/99 6172,0% K. Matias ISES Jan 2000

24. Carotid Stent Vitek et al. AJNR 2000 Incidence of complications:

25. Carotid Stent Antiplatelet therapy, before and after the procedure Antiplatelet therapy, before and after the procedure  Acute thrombosis of the stent  Embolism Vitek et al. AJNR 2000

26. Carotid Stent WALLSTENT TRIAL 219 patients 219 patients No protection No protection No antiplatelet therapy No antiplatelet therapy Surgical 4,5% Endovascular 12,1% Risk CVA/death Trial was interrupted Stroke 2001;32:325

27. Carotid Stent What to do with the plaque fragments

28. Carotid Stent Cerebral Protection

29. Carotid Stent There is considerable evidence of embolization during carotid angioplasty DeMonte et al. J Neurosurg. 1989;70:138 Ohki, T et al. J Vasc Surg. 1998;27:463

30. Carotid Stent Carotid artery stenting protected with an emboli containment system Whitlow PL, Lylyk P, Londero H, et al. Visible particles and debrís from plaques, cholesterol and calcific fragments # 22 to 667 particles with average size of 200 microns (range 3.6 to 5262) captured with cerebral protection system (PercuSurge) Stroke. 2002;33(5):1308-1314.

31. Embolic event is related to: Embolic event is related to: - Guidewire placement - Passage through the lesion - Dilation of the estenoses - Stent placement - Stent dilation (self or balloon expandable) Carotid Stent

32. J.Theron’s Technique Theron el al. AJNR, 1990 Carotid Stent

37. E.P.I. Carotid Stent

41. Risk factors for embolism: Risk factors for embolism: - Old age ( > 80 anos) - Arterial Hypertension - Recent stroke Al Mubarack et al. A J Cardiol, 1999

42. Carotid Stent Non contributing factors: Non contributing factors: - Gender - Neurologic symptoms - Coronary disease - Diabetes,  cholesterol, tabaco use - Bilateral lesion - Contralateral occlusion Matur et al. Circulation, 1998

43. Carotid Stent Clinical experience: Jacques TheronCVA/death = 2% Jacques TheronCVA/death = 2% Theron J. et al AJNR 1990;11:869 75 patientsCVA/death = 0 75 patientsCVA/death = 0 Whintlow P. CAFE study 2000 167 patientsCVA/death = 2,7% 167 patientsCVA/death = 2,7% Henry M. et al J Endovasc T 2002;9:1

44. Carotid Stent PTA/Stent NO/ cerebral protection (n=1596) 4,2% PTA/Stent WITH/ cerebral protection (n=771) 1,7% Global experience in cervical carotid artery stent placement. Wholey M H, Mathias K, et al. Cathet Cardiovasc Intervent. 2000;50(2):160 CVA/death

45. Carotid Stent Early outcome of carotid angioplasty and stenting with and without cerebral protection devices. Review of literature Kastrup A, Groschel K, Kraft H et al. PTA NO/ PROTECTION 5,5% 3,7% 1,1% 0,8% PTA WITH/ PROTECTION 1,8% 0,5% 0,3% 0,8% GLOBAL cva minor cva major death P < 0.001 P < 0.05 P = 0.6 Stroke 2003;34:813

46. Carotid Stent CAVATAS Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): A randomized trial. Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): A randomized trial. Lancet. 2001;357:1729-1737.

47. Carotid Stent CAVATAS 506 patients 506 patients 22 centers / 3 years 22 centers / 3 years Intervencionalists with small experience in carotid PTA. Intervencionalists with small experience in carotid PTA. Irregular use of stents Irregular use of stents No cerebralprotection No cerebralprotection Lancet. 2001;357:1729-1737.

48. Carotid Stent CAVATAS - RESULTS PTA Surgical CVA/death (30 days) 6,4% 5,9% CVA/death (30 days) 6,4% 5,9% CVA/death (> 7 days)10%9,9% CVA/death (> 7 days)10%9,9% Cranial nerve 08,7% Cranial nerve 08,7% Restenosis (1yr)14% 4% Restenosis (1yr)14% 4% No statistical differences in stroke risk between the two groups after 3 years. No statistical differences in stroke risk between the two groups after 3 years. Lancet. 2001;357:1729-1737.

49. Carotid Stent SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) 334 patients symptomatic or not with high risk (excluded from NASCET criteria) 334 patients symptomatic or not with high risk (excluded from NASCET criteria) Randomized Randomized Degre stenoses Degre stenoses Symptomatic > 50% Symptomatic > 50% Asynptomatic > 85% Asynptomatic > 85% 413 patients not randomized (registry) 413 patients not randomized (registry) Sponsored by Cordis - angioguard + precise Sponsored by Cordis - angioguard + precise

50. Carotid Stent SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) PTA/Stent technical success 95,6% Death, stroke, MI cummulative within 30 days or between 31 days and 1 year: PTA/Stent = 12.2% CEA = 20.1% Randomized group P = 0.047 Yadav JS, et al. NEJM OCT 2004

51. Carotid Stent SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) Stroke, death, MI < 30 days: PTA/Stent 4.8% CEA 9.8 % Stroke, death, MI Symptomatic at 1 yr PTA/Stent16.8 % CEA 16.5 %

52. Carotid Stent Technical Success = 95.9% - 99.3% Technical Success = 95.9% - 99.3% Particles in the filter (debrís) = 57% Particles in the filter (debrís) = 57% CVA/Death = 6,6% CVA/Death = 6,6% CVA/Death/MI = 7,8% CVA/Death/MI = 7,8% Degree of stenoses Degree of stenoses –Symptomatic > 50% –Asymptomatic > 80% ARCHeR TRIAL: Sponsored by Guidant: Accunet + Acculink

53. Carotid Stent ARCHeR 1 – Carotid Stent ARCHeR 1 – Carotid Stent – 158 patients ARCHeR 2 – Stent + Embolic Protection ARCHeR 2 – Stent + Embolic Protection – 278 patients ARCHeR 3 – Newer version Rapid exchange system + Embolic Protection ARCHeR 3 – Newer version Rapid exchange system + Embolic Protection –145 patients ARCHeR Trial – 581 combined patients Sponsored by Guidant: Accunet + Acculink

54. ARCHeR Trial – 581 combined patients 30 days combined end points

55. ARCHeR 1

56. ARCHeR 2

57. Carotid Stent TRIALS E REGISTERS

58. CREST CREST –2.500 Symptomatic patiens with low risk / 5 years –Randomized; 60 centers –Cerebral Protection –Sponsored by NIH / Guidant Carotid Stent

59. CARESS (Carotid Revascularization Using Endarterectomy or Stenting Systems) CARESS (Carotid Revascularization Using Endarterectomy or Stenting Systems) –439 patients –90% with >75% stenosis –68% asymptomatic –30-day mortality and stroke CEA 2% CEA 2% CSS 2% (with protection) CSS 2% (with protection) –30-day all-cause mortality, stroke, MI CEA 3% CEA 3% CSS 2% (with protection) CSS 2% (with protection)

60. Carotid Stent

61. Compreensive and proved experience in diagnostic cervico-cranial angiography (200 cases) Compreensive and proved experience in diagnostic cervico-cranial angiography (200 cases) Experience with PTA/stent Experience with PTA/stent Program Requirements for Residency Fellowship Education in Interventional Neuroradiology Higashida RT, Hopkins LN, Berenstein A et al. AJNR 2000; 21: 1153-1159

62. Carotid Stent Surgical treatment is still the “gold standard” for low risk patients Surgical treatment is still the “gold standard” for low risk patients More recent studies with cerebral protection devices are rapidly changing this concept. More recent studies with cerebral protection devices are rapidly changing this concept.

63. Carotid Stent In 2002 only 4% of carotid stenosis were treated by PTA and stents In 2002 only 4% of carotid stenosis were treated by PTA and stents Projections for year 2006 anticipate it will be 75% of all cases of carotid stenosis due to approval of the procedure/devices by the FDA in light of the clinical studies Projections for year 2006 anticipate it will be 75% of all cases of carotid stenosis due to approval of the procedure/devices by the FDA in light of the clinical studies Morgan & Stanley 2003

64. Carotid Stent Timing and frequency of complications after carotid artery stenting: What is the optimal period of observation? Tan KT, Cleveland TJ, Berczi V, et al. Safety criteria for same day discharge of patients 204 patients Incidence of complications = 5,4% 52,6% 6 hs 5,3% 6-12 hs 7,9%12-24 hs J Vasc Surg. 2003;38:236

65. Carotid Stent