Management of Carotid Artery Stenosis - Evidence and guidelines

Current Management of Carotid artery stenosis.
Comparison of Endarterectomy vs. Stenting.
Evidence review. Discussion of present guidelines.

1. CAROTID STENOSIS MANAGEMENT Satyam Rajvanshi Endarterectomy Stenting vs.

2. INTRODUCTION

3. STROKE 2 nd leading cause of death worldwide (after CAD) Majority of strokes (∼90%) are ischemic in nature Of these, 15% to 20% are attributed to carotid artery stenosis Primary prevention of ischemic stroke: a guideline from AHA/ASA Circulation 2006;113:e873–923 WHO data: 2015

4. Ischemic Stroke – Causes? CAUSE DICTATES MANAGEMENT LARGE VESSEL ATHEROEMBOLISM (most common) Artery to artery embolism    Thrombosis in situ SMALL VESSEL ATHEROEMBOLISM Lacunar disease associated with hypertension and diabetes LOW-FLOW STATE  Ischemic “watershed” areas CARDIOEMBOLISM Nonvalvular AF    Post-MI    Dilated cardiomyopathy    Prosthetic heart valves    Rheumatic heart disease  Infective endocarditis       Patent foramen ovale       

5. Ischemic Stroke – Causes? CAUSE DICTATES MANAGEMENT LARGE VESSEL ATHEROEMBOLISM (most common) Artery to artery embolism    Thrombosis in situ SMALL VESSEL ATHEROEMBOLISM Lacunar disease associated with hypertension and diabetes LOW-FLOW STATE  Ischemic “watershed” areas CARDIOEMBOLISM Nonvalvular AF    Post-MI    Dilated cardiomyopathy    Prosthetic heart valves    Rheumatic heart disease  Infective endocarditis       Patent foramen ovale       

6. Why Tackle the Carotid Lesion Mechanically?

7. It’s the natural history! ~ 30% of stroke survivors die within the first 12 months and two-thirds die within the next 12 years One ischemic stroke  incidence of a 2 nd stroke within 5 years of ~ 40% to 50% Primary prevention of ischemic stroke: a guideline from AHA/ASA Circulation 2006;113:e873–923

8. It’s the natural history! Stroke risk in Carotid artery stenosis Carotid symptoms? Severity of stenosis ? Others - Plaque composition? Plaque ulceration? Circulation 2006;113:e873–923 NEJM 1998;339:1415-25

9. It’s the natural history! TIA secondary to significant carotid artery stenosis  ~ 30-40% risk of stroke within the next 5 years In symptomatic patients, 2-year risk – 22% with 50%-69% (moderate) stenosis vs. 26% in 70% - 99% (severe) stenosis Circulation 2006;113:e873–923 NEJM 1998;339:1415-25

10. It’s the natural history! In asymptomatic patients, 5-year risk – 7.8% with <50% stenosis vs. 18.5% in 75% - 95% stenosis Circulation 2006;113:e873–923

11. L ow medical treatment efficacy! Relative risk reduction with medical treatment is no more than 25% CEA provides better protection against future events – proven in RCTs Primary prevention of ischemic stroke: a guideline from AHA/ASA Circulation 2006;113:e873–923

12. CEA/BMT vs. BMT alone

13. Silent disease burden and stroke risk? Estimated incidence of asymptomatic extracranial carotid stenosis in >65 year olds >50% stenosis – 5 to 10% >80% (Critical) – less than 1% Annual risk of stroke in asymptomatic >50% stenosis – from <1% to 4.3% But 80% stroke occur without recognizable warning symptoms ! Circulation 2006;113:e873–923 JACC 2014;64:722-31

14. History in brief

15. Carotid Endarterectomy (CEA) 1920s - Introduction of cerebral angiography. Carotid artery disease was found among persons with stroke 1950s - C.M. Fisher called attention to atherosclerosis involving the carotid bifurcation as an important cause of stroke and suggested surgery as a possible therapy 1954 - De Bakey performed the 1 st carotid endarterectomy

16. Carotid Angioplasty 1980 - 1 st POBA by Kerber 2 major complications Acute closure Distal embolization 1996 – CAS  Roubin et al Tackled acute closure 1996 – CAS + EPD  Theron et al To  d istal embolization Patient & lesion selection Meticulous technique Embolic protection devices Am J Neuroradiol 1980;1:348-9 Am J Cardiol 1996;78:8-12 Radiology 1996;201:627-36

17. Carotid Angioplasty 1980 - 1 st POBA by Kerber 2 major complications Acute closure Distal embolization 1996 – CAS  Roubin et al Tackled acute closure 1996 – CAS + EPD  Theron et al To  d istal embolization Patient & lesion selection Meticulous technique Embolic protection devices Palliation in the inoperable ? Equivalence to Surgery ? Superiority to Surgery Am J Neuroradiol 1980;1:348-9 Am J Cardiol 1996;78:8-12 Radiology 1996;201:627-36

18. And then started the debate…

19. CEA vs CAS Where do we stand?

20. high surgical risk ± symptoms

21. SAPPHIRE NEJM 2004;351:1493-1501

22. SAPPHIRE RCT: 167 pts each in CEA vs CAS group

23. SAPPHIRE CAS (Self expanding nitinol stent – Smart or Precise) with EPD (Filter basket – Angioguard )

24. SAPPHIRE Primary end point of the study - cumulative incidence of a major cardiovascular event at 1 year — a composite of death , stroke, or myocardial infarction within 30 days after the intervention or death or ipsilateral stroke between 31 days and 1 year P=0.053

25. SAPPHIRE 3 yr NEJM 2008;358:1572-9

26. SAPPHIRE 3 yr Prespecified major end point , defined as death, myocardial infarction, or stroke within 30 days or death or ipsilateral stroke between 31 days and 1080 days

27. Symptomatic + average surgical risk

28. SPACE Lancet 2006;368:1239-47

29. SPACE 1214 pts Symptomatic severe stenosis (>70% ECST or >50% NASCET) CAS by inexperienced operators EPD not necessary – used in 27% only Stopped early due to futility

30. SPACE Freedom from primary outcome – difference larger than non-inferiority margin

31. SPACE 2 yr Lancet 2008;7:893-902

32. SPACE 2 yr CAS noninferior to CEA at 2 years!

33. EVA-3S NEJM 2006;355:1660-71

34. EVA-3S 527 pts Symptomatic severe stenosis (>60% NASCET) CAS by inexperienced operators – only required to perform 2 CAS before being eligible Surgeons were relatively experienced – atleast 25 CEA before being eligible! EPD used in 91% only – not in all because not mandatory in 1 st 2 yrs Stopped early due to futility

35. EVA-3S CAS had RR of 2.5 vs CEA for any stroke/death at 30 days!

36. EVA-3S 4 yr Lancet Neurol 2008;7:885-92

37. ICSS Lancet 2010;375:985-97

38. ICSS 1713 pts Symptomatic severe stenosis (>50% NASCET) CAS by operators with atleast 10 CAS experience CEA by operators with atleast 50 CEA experience! EPD used in 72% only

39. ICSS

40. ICSS 5 yr Lancet 2015;385:529-38

41. ICSS 5 yr Fatal or disabling stroke Periprocedural stroke or Periprocedural death Any stroke All cause death

42. CREST NEJM 2010;363:11-23

43. CREST 2502 pts Symptomatic stenosis (>50% ECST; >70% on USG; >70% on CT/MRI if 50-69% on USG) – 1321 pts Asymptomatic stenosis (>60% ECST ; >70% on USG; >80% on CT/MRI if 50-69% on USG) – 1181 pts Standard stroke detection protocol in follow-up EPD use mandatory whenever feasible – used in 96.1%

44. CREST Primary end point - composite of stroke, MI, or death from any cause during the periprocedural period or ipsilateral stroke within 4 years after randomization

45. CREST 10 yr NEJM 2016;374:1021-31

46. CREST 10 yr No difference in primary end-point Only periprocedural strokes more in CAS – that too minor strokes

47. CREST 10 yr Restenosis - >70% on USG on routine annual follow-up exam No difference - 12.2% in CAS vs 9.6% in CEA

48. CREST 10 yr

49. JACC 2011 – Non RCT real world trial

50. Asymptomatic + average surgical risk

51. ACT 1 NEJM 2016;374:1011-20

52. ACT 1 1453 pts Stopped early due to slow enrollment Asymptomatic severe stenosis – free from ipsilateral TIA/stroke in last 6 months (>70% ECST or >70% on USG; without >60% contralateral stenosis ) CAS by experienced operators Closed cell tapered nitinol stent ( Xact stent) with Distal EPD ( Emboshield ) - used in 97.8%

53. ACT 1 Freedom from death, stroke, and MI within 30 days and from ipsilateral stroke within 365 days after the procedure in ITT population

54. CEA vs CAS vs BMT

55. CEA vs CAS vs BMT RCT ongoing CREST 2 – Asymptomatic pts at average surgical risk ECST 2 – Asymptomatic and Low risk symptomatic pts

56. Overall comparison CEA vs CAS Characteristics CEA CAS General anesthesia requirement/complication ↑↑ ↓ Periprocedural MI ↑↑ ↓ Periprocedural minor stroke ↓ ↑ Periprocedural major stroke = = Cranial nerve damage ↑↑ ↓ Longer recovery ↑ ↓ Wound complication ↑ ↓

57. Guide to choose one over other

58. Best strategy? Patient factors Age, comorbidities , life expectancy, functional status, patient preference Disease factors Risk of stroke, anatomy, resources

59. Based on review of 192 papers on carotid stenosis management 1 point to each favourable character; 3 points to each absolute character Higher number of points indicate that strategy has better evidence Equal points – patient preference!

60. guidelines

61. conclusions

62. CONCLUSIONS CAS has probably achieved a clinical equipoise with CEA Operator experience is key to successful and efficient CAS RCT with BMT arm are needed in asymptomatic pts and are ongoing Individualized management strategy is the answer to this problem – no place for ‘one size fits all’

63. Thank You . . .

64. CREST

65. ACT 1