1. Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis Dr. Quan, Dr. Mirhashemi, Dr. Chiang N Engl J Med 2006; 355:1660-71

2. Objective 1. Know when to send patients for carotid artery stenting vs endarterectomy 2. Learn about Relative Risk 3. Know when is Relative Risk significant

3. Overview Step 1 – Get patients with symptomatic carotid stenosis Step 1 – Get patients with symptomatic carotid stenosis Step 2 – Send patients to have carotid stenting or endarterectomy Step 2 – Send patients to have carotid stenting or endarterectomy Step 3 – Evaluate 30-day stroke or death of both groups Step 3 – Evaluate 30-day stroke or death of both groups

4. Purpose To evaluate the efficacy of carotid stenting vs endarterectomy in patients with symptomatic carotid- artery stenosis To evaluate the efficacy of carotid stenting vs endarterectomy in patients with symptomatic carotid- artery stenosis

5. Time and Place November 2000 to September 2005 November 2000 to September 2005 20 academic and 10 non-academic centers in France 20 academic and 10 non-academic centers in France Approved by ethics committee Approved by ethics committee

6. Centers and Investigators 1+ Neurologist 1+ Neurologist 1+ Vascular Surgeon 1+ Vascular Surgeon Performed 25 endarterectomies Performed 25 endarterectomies 1+ Interventional Physician 1+ Interventional Physician Performed 12 carotid-stenting or Performed 12 carotid-stenting or Performed 35 stenting procedures in supraaortic trucks (5 in carotid artery) Performed 35 stenting procedures in supraaortic trucks (5 in carotid artery)

7. Patients 18+ years old 18+ years old Hemispheric or retinal TIA or nondisabling stroke within 120 days Hemispheric or retinal TIA or nondisabling stroke within 120 days Carotid Artery Stenosis of 60 to 99% Carotid Artery Stenosis of 60 to 99% Confirmed by angiography or both duplex scanning and MRA Confirmed by angiography or both duplex scanning and MRA

8. Reference: http://neuro.wehealny.org/endo/proc_stents-angioplasty.asp

9. Reference: http://www.diagnosticclinic.com/health/articles/images/MRA/carotid_stenosis.jpg

10. Excluded Patients Modified Rankin score of 3+ Modified Rankin score of 3+ Nonatherosclerotic carotid disease Nonatherosclerotic carotid disease Severe tandem lesions (proximal common carotid artery or intracranial artery that was more severe than carotid lesion) Severe tandem lesions (proximal common carotid artery or intracranial artery that was more severe than carotid lesion) Previous revascularization Previous revascularization History of bleeding disorder History of bleeding disorder

11. Excluded Patients Uncontrolled HTN or DM Uncontrolled HTN or DM Unstable Angina Unstable Angina Contraindication to heparin, ticlopidine, or clopidogrel Contraindication to heparin, ticlopidine, or clopidogrel Life expectancy of less than 2 years Life expectancy of less than 2 years Percutaneous or surgical intervention within 30 days Percutaneous or surgical intervention within 30 days

13. Standard Procedures Surgeons performed endarterectomy according to customary practice Surgeons performed endarterectomy according to customary practice Carotid stenting via femoral route with the use of cerebral protection device (01/2003 approved by safety committee) Carotid stenting via femoral route with the use of cerebral protection device (01/2003 approved by safety committee)

14. Cerebral Protection Device Reference: http://radinfo.musc.edu/Interventional/index.php?module=pagemaster&PAGE_user_op=view_page&PAGE_id=58

15. Endarterectomy

19. Anticoagulation Aspirin 100-300mg qd Aspirin 100-300mg qd Clopidogrel 75 mg qd or Clopidogrel 75 mg qd or Ticlopidine 500mg qd Ticlopidine 500mg qd Take 3 days before and 30 days after stenting Take 3 days before and 30 days after stenting

20. Follow-up 48 hours 48 hours 30 days 30 days 6 months after treatment 6 months after treatment Then every 6 months thereafter Then every 6 months thereafter

21. End Points Any stroke or death occurring within 30 days after treatment Any stroke or death occurring within 30 days after treatment

22. Results

23. Predicted Statistics Require 872 patients whether stenting was not inferior to endarterectomy with regard to the 30-day incidence of stroke or death Require 872 patients whether stenting was not inferior to endarterectomy with regard to the 30-day incidence of stroke or death Expected 30-day incidence of stroke or death (Endarterectomy 5.6%, Stent 4%) Expected 30-day incidence of stroke or death (Endarterectomy 5.6%, Stent 4%)

26. Local Injuries Cranial-nerve injury was significantly more common after endarterectomy than after stenting (7.7% vs 1.1%, P<0.001) Cranial-nerve injury was significantly more common after endarterectomy than after stenting (7.7% vs 1.1%, P<0.001) Median hospital stay (stent, 3 days, endarterectomy – 4 days, P=0.01) Median hospital stay (stent, 3 days, endarterectomy – 4 days, P=0.01)

27. Weakness by Dr. Mirhashemi by Dr. Mirhashemi

28. Strengths Baseline patients characteristics in stenting vs endarterectomy are statistical similar Baseline patients characteristics in stenting vs endarterectomy are statistical similar

31. Adjusted Relative Risk Age – 2.4 Age – 2.4 History of stroke – 2.6 History of stroke – 2.6 More patients in the stenting group had contralateral carotid occlusion; none of them had a stroke after stenting More patients in the stenting group had contralateral carotid occlusion; none of them had a stroke after stenting

32. Strength Computer-generated sequence randomly assigned to undergo endarterectomy or stenting Computer-generated sequence randomly assigned to undergo endarterectomy or stenting Operator independent Operator independent

33. Learning Curve No significant differences in outcome related to the number of stenting procedures performed in individual centers or to the experience of the interventional physicians No significant differences in outcome related to the number of stenting procedures performed in individual centers or to the experience of the interventional physicians Experience with any new device was required before its use in the trial Experience with any new device was required before its use in the trial

34. Effects of Cerebral Protection 30-day incidence of stroke or death was lower among patients who underwent stenting with cerebral protection (7.9%) than stenting alone (25%) 30-day incidence of stroke or death was lower among patients who underwent stenting with cerebral protection (7.9%) than stenting alone (25%) However, the RR over endarterectomy did not differ significantly (2.0 before and 3.4 after) However, the RR over endarterectomy did not differ significantly (2.0 before and 3.4 after)

35. Antiplatelet Therapy 30-day incidence of stroke or death after stenting didn’t differ significantly between pts who received dual antiplatelet therapy (19 of 211, 9.0%) and those who received single antiplatelet therapy (4 of 36, 11.1%, P=0.75) 30-day incidence of stroke or death after stenting didn’t differ significantly between pts who received dual antiplatelet therapy (19 of 211, 9.0%) and those who received single antiplatelet therapy (4 of 36, 11.1%, P=0.75)

36. Strengths The events committee assess the occurrence of stroke, death, and other outcomes, unaware of the treatment assignments The events committee assess the occurrence of stroke, death, and other outcomes, unaware of the treatment assignments

37. Discussion Lower surgical risk in our study Lower surgical risk in our study Previous trials – 30-day incidence of stroke or death after endovascular repair of the carotid artery is 8.1% (51 of 632) Previous trials – 30-day incidence of stroke or death after endovascular repair of the carotid artery is 8.1% (51 of 632)

38. Stenting 30-day incidence of stroke after stenting in our study 9.2% which was higher than SAPPHIRE trial 3.6% (most patients had asymptomatic stenosis) 30-day incidence of stroke after stenting in our study 9.2% which was higher than SAPPHIRE trial 3.6% (most patients had asymptomatic stenosis)

40. Safety and Futility September 2005, safety committee recommended stopping enrollment due to increased risk of stroke or death after stenting and requiring to enroll more than 4000 patients to test the noninferiority of stenting September 2005, safety committee recommended stopping enrollment due to increased risk of stroke or death after stenting and requiring to enroll more than 4000 patients to test the noninferiority of stenting

41. Conclusion Patients with symptomatic carotid stenosis of 60% or more, treatment with endarterectomy results in lower rates of stroke or death at 30days and 6 months than does stenting. Patients with symptomatic carotid stenosis of 60% or more, treatment with endarterectomy results in lower rates of stroke or death at 30days and 6 months than does stenting.

42. THANK YOU… THANK YOU…