Medstar Washington Hospital Center Carotid Artery Disease Past, Present & Future Who should have an intervention in 2017? Rajesh Malik M.D., FACS Vascular Surgery Medstar Washington Hospital Center

Disclosure Statement of Financial Interest I, Rajesh Malik, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

Overview Stroke 2nd leading cause of death U.S. 500,000 strokes/year 3 million stroke survivors 35% of carotid origin

Carotid Stenosis History Fisher 1951 Ischemic stroke & “occlusion of the internal carotid artery”

Earliest Reported Case Resection, anastomosis Eastcott and Rob St. Mary’s Hospital, May 19th, 1954

Carotid Artery Pathology Atherosclerosis Fibromuscular Dysplasia Coils/Kinks Aneurysms Takayasu's Arteritis Radiation

Carotid Stenosis Clinical syndromes Asymptomatic Symptomatic TIA - brief episode of focal loss of brain function < 24 hrs, 2-15 minutes RIND - >24hrs, <1 week. Stroke

Imaging Duplex sonography Accurate Non-invasive Plaque characteristics Screening Intraop, postop

Imaging MRA Non-invasive Non-nephrotoxic Assess cerebral circulation May overestimate degree of occlusion

Imaging Angiography Gold standard Plaque characteristics Invasive Risk of stroke Iodinated contrast

Copyright © 2015 American Medical Association. All rights reserved. From: Management of Asymptomatic Internal Carotid Artery Stenosis JAMA. 2013;310(15):1612-1618. doi:10.1001/jama.2013.280039 Table Title: Level 1 Studies in Revascularization of Asymptomatic Carotid Artery Stenosis Disease Date of download: 5/4/2015 Copyright © 2015 American Medical Association. All rights reserved.

Randomized Trials Asymptomatic Surgical + Medical Medical ACAS 5 year > 60% stenosis death/stroke/TIA 5.1 % 11 % * Highly sig 30 day actual study halted death /stroke 1.5 % angio death/stroke 1.2 %

The benefit of surgery was greater for men than women (reduction in risk, 66% vs. 17%) The rate of perioperative complications was higher among women than men (3.6% vs. 1.7%).

Randomized Trials Symptomatic surgical + medical medical NASCET 2 year 9 % 26 % 70-99% death/stroke (p=0.001) 30 day 5.5 % 3.3 % death/stroke NASCET 5 year 16 % 22 % 50-69% death/stroke (p=0.045) ECST 3 year 70-99% death/stroke/ 12% 22% (p=0.001) 30 day death /stroke 7.5 %

NASCET

Carotid Endarterectomy Surgical complications 7.6 % cranial nerve injury 5.5 % wound hematoma 3.4 % wound infection 3.9 % cardiovascular (MI, CHF, PVCs) 81% considered to be minor NASCET New Engl J Med 1991

Carotid Endarterectomy Indications - Asymptomatic Proven stenosis > 60% Uncertain high risk patient surgeon morbidity-mortality >3% combined carotid coronary operation non-stenotic ulcerative lesions Inappropriate Morbidity-mortality rate >5% Ad hoc committee, Stroke council, AHA, 1995

Carotid Endarterectomy Indications - Symptomatic Proven stenosis > 70% Acceptable stenosis 50-69% Uncertain symptomatic acute thrombosis Inappropriate stenosis <50%, not on aspirin Ad hoc committee, Stroke council, AHA, 1995

Carotid Endarterectomy Technical controversies Anesthesia Shunting Patch angioplasty

Carotid Endarterectomy Anesthesia Local patient monitoring avoid general anesthesia General compliance decrease cerebral metabolism increase cerebral blood flow

Shunting Pitfalls Dissection Embolization Flap

Carotid Endarterectomy Patch angioplasty Recurrent stenosis more likely in: women smokers small ICA Prospective randomized trials - patch  recurrent stenosis

CAS vs. CEA CAS CEA

Carotid Stenting The goal

Carotid Stenting The problem

Quantification of emboli Transcranial Doppler 202±119 52±64 Number of hits CAS CEA Procedure Crawley F, Clifton A, Buckenham T, et al. Comparison of hemodynamic cerebral ischemia and microembolic signals detected during CEA and CAS. Stroke 1997

Cerebral Protection Devices The Solution? Distal balloon occlusion Distal filters Proximal balloon occlusion

Distal Filter Angioguard

Distal Filter MedNova

Carotid Stenting Early Results 30 day Study No. TIA Stroke Death Death/Stroke Wholey 2001 472 3.1 % 2.9 % 1.3 % 4.2 % Dangas 2001 39 2.6 % 2.6 % 0 % 2.6 % Roubin 2001 604 5.8 % 1.6 % 7.4 % Parodi 2000 46 4.3 % 0 % 4.3 % Henry2000 315 1.3 % 2.9 % 0.3 % 3.2 % Wholey 2000 4757 2.8 % 4.2 % 0.8 % 5.0 %

CEA vs. CAS Alberts, et al. Stroke 2001 First multicenter, randomized prospective study Wallstent, no protection CAS vs. CEA: 30 day complication - 12.1% vs. 4.5% ipsi stroke/ death (1 year) - 12.1% vs. 3.6% any major stroke (1 year) - 3.7% vs. 0.9% Study terminated early based on futility analysis

CAS Trials CREST (NIH) – symptomatic, mimic NASCET ICAROS – Imaging: CAS & risk of stroke Cordis – Angioguard & Smart MedNova – MedNova stent&filter CAFÉ USA (phase 2): Wallstent & Percusurge Many more to come: CAVATAS II, EVA, … Databanks: EUROCAST,….

The CREST Trial (2010) Methods: Randomized trial comparing CEA and CAS in 2502 patients with CA stenosis (both symptomatic and asymptomatic) Composite end point- stroke, MI or death from any cause during 30 days post-op or any ipsilateral stroke within 4 yrs of treatment Results: No significant difference in composite primary end point after 4 yrs No difference for symptom status or sex 4 year rate of stroke or death in asymptomatic patients 4.5% in CAS and 2.7% in CEA Higher rates of MI in CEA group (1.1% CAS vs. 2.3% CEA) Higher rates of stroke in CAS group (4.1% CAS vs. 2.3% CEA) Higher rates of Cranial Nerve Palsies in CEA (0.3% CAS vs. 4.7% CEA)

CREST Results Cont. Differential effects of Age: Outcomes were slightly better after CAS for patients aged <70 years and better after CEA for patients aged >70 years. Quality of Life Survey: At 1 year, periprocedural stroke had an effect on the physical component summary scale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) Periprocedural MI had no effect Rates of Restenosis: Similar rates of restenosis/occlusion (6.0% CAS vs. 6.3% CEA) Note: smoking predicted increased restenosis rate after CEA only

Brott TG et al. N Engl J Med 2010;363:11-23. Primary End Point, According to Treatment Group. Figure 2. Primary End Point, According to Treatment Group. The primary end point was a composite of stroke, myocardial infarction, or death from any cause during the periprocedural period or ipsilateral stroke within 4 years after randomization. Panel A shows the Kaplan–Meier curves for patients undergoing carotid-artery stenting (CAS) and those undergoing carotid endarterectomy (CEA) in whom the primary end point did not occur, according to year of follow-up. Panel B shows the hazard ratios for the primary end point, as calculated for the CAS group versus the CEA group, according to age at the time of the procedure. The hazard ratios were estimated from the proportional-hazards model with adjustment for sex and symptomatic status. Dashed lines indicate the 95% confidence intervals. Panel C shows the numbers of patients in each age group. Brott TG et al. N Engl J Med 2010;363:11-23.

In what groups might we consider CAS? SAPPHIRE Trial (NEJM 2006) – non-inferiority study Patients (asymptomatic and symptomatic) with carotid stenosis and other co-morbidities placing them at high risk for surgery. At least one of the following criteria were required Clinically significant heart disease Severe pulmonary disease Contralateral carotid occlusion Contralateral laryngeal nerve palsy Previous radical neck surgery or radiation therapy Recurrent stenosis after endarterectomy Age >80 yrs

Relative Contraindications for CEA History of prior neck irradiation Concurrent tracheostomy Prior radical neck dissection with or without radiation Contralateral vocal cord paralysis from prior endarterectomy Atypical lesion location, either high or low that is surgically inaccessible Severe recurrent carotid stenosis Unacceptably high medical risk

SVS guidelines The committee recommends CEA as the first-line treatment for most symptomatic patients with stenosis of 50% to 99% and asymptomatic patients with stenosis of 60% to 99%. CAS should be reserved for symptomatic patients with stenosis of 50% to 99% at high risk for CEA for anatomic or medical reasons. CAS is not recommended for asymptomatic patients at this time Asymptomatic patients at high risk for intervention or with <3 years life expectancy should be considered for medical management as the first-line therapy

Future The Carotid Revascularization Endarterectomy Stenting Trial 2 (CREST 2) is currently recruiting subjects with asymptomatic carotid artery stenosis and ≥70% stenosis. The study will compare either OMT alone versus OMT plus CEA or OMT alone versus OMT plus CAS. The Stent-Protected Angioplasty in Asymptomatic Carotid Artery Stenosis versus Endarterectomy (SPACE-2) study aims to recruit about 3,500 patients and randomly assign them to OMT alone or CEA or CAS.

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