To Stent or Not to Stent? Treatment of Carotid Artery Stenosis in the 21 st Century

1. To Stent or Not to Stent? Treatment of Carotid Artery Stenosis in the 21st Century Robert R. Carter MD April 21st 2010 Grand Rounds Department of Vascular Surgery University of Kentucky

2. Goals • Review history of carotid artery disease • Summarize evidence for surgical intervention • Summarize trials that compare stenting and carotid endarterectomy (CEA) • Review FDA approved indications for stenting

3. 1875 • First report linking stroke with extra cranial vascular disease by Sir William Richard Gowers. • Described a patient with right hemiplegia and blindness in the left eye. • He attributed this syndrome to an occlusion of the left carotid artery in the patient’s neck.

4. 1914 • James Ramsay Hunt emphasized extra cranial carotid artery occlusive disease as a cause of stroke. • Urged examination of the cervical portion of the carotid artery during autopsy. • Suggested that transient cerebral ischemia was equivalent to intermittent claudication of the brain and represented a prodrome to a major stroke.

5. 1937 • Egas Moniz reported that arteriography could be used to diagnose carotid artery occlusion.

6. What is a TIA? • What is a Stroke? • How are they related?

7. Transient Ischemic Attack (TIA) • Definition • Any transient neurologic deficit lasting from several seconds to many hours but not longer than 24 hours.

8. TIA • Two mechanisms • a brief vascular spasm in a partially blocked artery impedes blood flow to the brain temporarily • Small “mini” strokes where pieces of plaque dislodge and embolize • Not benign • Degree of cerebral atrophy and infarction linked to number of TIA’s

9. Amaurosis Fugax • Definition • temporary monocular blindness (shade coming down over the eye) caused by embolization to the ophthalmic artery (first branch off the internal carotid artery) • TIA • Ulcerated plaque at common carotid bifurcation usual source

10. Amaurosis Fugax • Fundoscopic exam shows plaque traversing the retina • First described by Robert W. Hollenhorst in 1961 • Hollenhorst bodies

11. Stroke • Definition • A sudden loss of brain function caused by an interruption in the supply of blood to the brain. A ruptured blood vessel or cerebral thrombosis may cause the stroke, which can occur in varying degrees of severity from temporary paralysis and slurred speech to permanent brain damage and death. • Neurologic deficit lasts longer than 24 hours

12. How are TIA and stroke related? • 35% of patients with a TIA will have a stroke in their lifetime • 50% of these will occur in the year following first TIA • After first year stroke risk is 5% per year

13. Stroke • 3rd leading cause of death in the united states • 2nd most common cause of cardiovascular death • #1 cause of death from a neurologic disorder

14. http://www.cdc.gov/

15. Stroke • Incidence of new stroke is 160/100,000 • Annual financial impact estimated to be $45.3 billion/year • Death • Disability • Long term care • Medical expenses • Inability to return to previous employment

16. Stroke • Prognosis • 80% survive initial event • 29% regain normal function • 36% return to work • 18% unable to work, but can take care of themselves • 4% require custodial care • Natural history • only 50% of stroke victims will be alive at five years.

17. Is TIA a risk factor for stroke? • 33% of TIA patients will suffer a stroke within 5 years, 17% within 1 year • What about asymptomatic carotid stenosis?

18. Outcome in patients with asymptomatic neck bruits 1986 • NEJM • prospectively followed 113 asymptomaticpatients with carotid stenosis ≥ 75% (Doppler) • 1 year 18% had ischemic cerebrovascular events over ¼ of these events strokes (5.5%) • At 2 years 22% had ischemic cerebrovascular events • In patients with less than 75% stenosis • 1 year 3% • 2 years 6% Chambers BR, Norris JW. Outcome in patients with asymptomatic neck bruits. N Engl J Med 1986;315:860-865

19. Outcome in patients with asymptomatic neck bruits 1986

20. What is the risk of stroke with asymptomatic carotid stenosis? • With ≥ 75% asymptomatic stenosis, 22% of patients will have an ischemic cerebrovascular event at 2 years • What can we do about it?

21. Medical Treatment • Both systolic and diastolic blood pressure independently related to stroke incidence • 6mm reduction in DBP produces 42% reduction in stroke rate • Tx of isolated systolic hypertension in patients over 60 reduces stroke incidence by 32% • Smoking cessation • Relative risk 1.5-2.2 • Serum lipid levels • have not been shown to affect stroke rate but low levels slow progression of atherosclerosis Biller J, Feinberg WM, Castaldo JE, et al. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a special writing group of the stroke council, american heart association. Circulation 1998;97:501-509

22. Medical Treatment • Alcohol consumption • Heavy alcohol use associated with excessive stroke risk • Moderate consumption may have no or a slightly protective effect • Antiplatelet therapy • 23% reduction in stroke with aspirin compared to placebo in patients with history of TIA/stroke • Also 22% reduction in MI/death Biller J, Feinberg WM, Castaldo JE, et al. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a special writing group of the stroke council, american heart association. Circulation 1998;97:501-509

23. CEA • Carotid Endarterectomy • Surgical removal of the inner layer of the carotid artery when narrowed by atheromatous intimal plaques

24. 1953 • KJ Strully attempted (unsuccessfully) to operate on an occluded carotid artery.

25. 1954 • First successful extra cranial carotid surgery preformed by Felix Eastcott. • Patient with episodes of hemispheric cerebral ischemic attacks and an atherosclerotic lesion at the carotid bifurcation. • Treated with resection and primary anastomosis. Eastcott HHG, Pickering GW, Rob CG. Reconstruction of internal carotid artery in a patient with intermittent attacks of hemiplegia. Lancet 1954;2:994-6.

26. 1953? • Michael DeBakey published a similar operative case preformed prior to Eastcott’s case. • However his report was published after Eastcott’s case and thus Eastcott is credited with bringing the possibility of carotid artery repair to medical attention.

27. 1966 • Drs. Stanley Crawford and Michael DeBakey credited with first describing carotid endarterectomy in 1966. (although DeBakey claimed to have preformed it in 1953)

28. Cooley • Dr. Denton Cooley is credited with being the first to use an intravascular shunt during carotid surgery • Professional rivalry with DeBakey that lasted 40 years, made public amends November 7, 2007 at ages 99 and 87

29. Cooley • When asked by a Lawyer if he considered himself the best heart surgeon in the world he answered in the affirmative. • The lawyer then asked if he thought he was being rather immodest? • Cooley replied, “Perhaps, but remember I am under oath.”

30. Does medical therapy decrease risk of stroke? • Smoking cessation, BP control, etoh in moderation and antiplatelet therapy all reduce stroke risk • What about CEA?

31. NASCET 1991 • North American Symptomatic Carotid Endarterectomy Trial (50 centers US and Canada) • TIA or non disabling stroke within 120 days with 30-99% stenosis • Patients randomized to medical or surgical therapy • Patients symptomatic with high grade lesions (70 - 99% stenosis), 659 patients, <80 years old • Results • 24% medically managed patients had stroke within 18 months • 7% surgical patients had a stroke • Rate of perioperative major stroke/death was 2.1% in this trial Nascet C. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991;325:445-53

32. NASCET 1991 • Study stopped early • Risk reduction at 2 years • 12% 70-79% stenosis • 18% 80-89% stenosis • 26% 90-99% stenosis • Conclusion • CEA highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or non disabling strokes and ipsilateral high-grade stenosis (70-99%) of the internal carotid artery.

34. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis 1991 • 189 symptomatic patients >50% ipsilateral stenosis at 16 VA hospitals • Randomized to CEA or medical management • At 1 year • 7.7% stroke/TIA rate in CEA group • 19.4% stroke/TIA rate in medical group Mayberg MR, Wilson SE, Yatsu F, et al. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. JAMA 1991;266:3289-3294.

36. NASCET 1998 • Does CEA benefit symptomatic pts with stenosis <70% • Any ipsilateral stroke at 5 years • 50-69% stenosis • 15.7% CEA • 22.2% medical • <50% stenosis • 14.9% CEA • 18.7% medical (not statistically significant)

38. NASCET 1998 • CEA in symptomatic patients with 50-69% yields only moderate reduction in risk of stroke and provided no benefit to patients with <50% stenosis. • Patients with ≥70% stenosis had durable benefit at eight years.

39. Can CEA reduce the stroke risk in symptomatic patients? • CEA reduces the risk of any stroke from 25% to 10% at two years in patients with symptomatic stenosis of ≥ 70% (NASCET) • Can CEA reduce the stroke risk in asymptomatic patients?

40. Veterans Affairs Trial, 1993 • Asymptomatic Carotid Stenosis Veterans Administration Study • 11 centers, 1983-1991 • 444 men with asymptomatic carotid stenosis • 50% stenosis or more (angiogram) • Evaluated combined incidence of TIA, Amaurosis Fugax, and stroke • Randomized to optimal medical treatment alone vs. optimal medical treatment plus carotid endarterectomy Hobson RW 2nd, Weiss DG, Fields WS, Goldstone J, Moore WS, Towne JB, Wright CB. Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. The Veterans Affairs Cooperative Study Group. N Engl J Med. 1993 Jan 28;328(4):221-7.

41. Veterans Affairs Trial, 1993 • All patients followed for an average of 48 months • Incidence of ipsilateral neurologic events • 8% CEA • 20.6% medical group • Stroke/death rate within 30 days not different between groups

42. Veterans Affairs Trial, 1993 Incidence of Neurologic End Points for Ipsilateral Events.

43. Veterans Affairs Trial, 1993 Kaplan-Meier Curves for Event-free Rates of First Ipsilateral Stroke and Transient Ischemic Attack Including Transient Monocular Blindness.

44. ACAS, 1995 • Asymptomatic Carotid Artery Study • Prospective randomized trial • 39 sites in the US and Canada • 1987-1993, 1662 patients with asymptomatic carotid artery stenosis 60% or greater • Daily aspirin administration and medical risk factor management for all patients • Medical vs. carotid endarterectomy Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for Asymptomatic Carotid Artery Stenosis. JAMA, 273(18), 10 May 1995, pp 1421-1428

45. ACAS, 1995 • Outcomes • Cerebral infarction occurring in the distribution of the study artery, any stroke or death • Perioperative risk • 30 days post op 2.3% in the surgery group • 42 days post randomization 0.4% in the medical group • Median follow-up 2.7 years • Combined risk of outcomes • 5.1% CEA • 11% medical management

47. ACAS, 1995

48. ACAS, 1995

49. ACAS, 1995

50. Can CEA reduce the stroke risk in asymptomatic patients? • CEA reduces the risk of any stroke or death from 11% to 5% at five years in patients with asymptomatic stenosis of ≥ 60% (ACAS) • What about stenting?