J A M E S T D E V R I E S , M D , F A C C , F S C A I A S S I S T A N T P R O F E S S O R O F M E D I C I N E

G E I S E L S C H O O L O F M E D I C I N E A T D A R T M O U T H D I R E C T O R , C A R D I A C C A T H E T E R I Z A T I O N L A B D A R T M O U T H - H I T C H C O C K M E D I C A L C E N T E R

Carotid Revascularization: Who, When, and How

DISCLOSURES

None of the planners or presenters of this session have disclosed any conflict or commercial interest

Carotid Revascularization: Who, When, and How

OBJECTIVES:

1. Describe symptomatic and asymptomatic carotid artery disease.

2. Review the research related to revascularization. 3. Explain which procedure is indicate depending on the

specific patient evaluation.

Outline

Background Part 1: Asymptomatic carotid disease Part 2: Symptomatic carotid disease Part 3: Stenting versus surgery Overall conclusions

PART 1: Asymptomatic Carotid Stenosis

Clinical Question #1

A 67 yo male is seen in clinic follow up. He has an asymptomatic left carotid bruit and a duplex demonstrates a 50-79% stenosis of the left internal carotid artery. He has known CAD and hyperlipidemia and is on aspirin and atorvastatin. He has a normal creatinine. The one year risk for an ipsilateral stroke is:

A. 1% B. 3% C. 5-7% D. >10%

Clinical Question #2

The patient in question #2 wants the best therapy possible for his carotid stenosis, telling you “I don’t want a stroke.” You recommend:

A. . Add clopodigrel (Plavix) to his medications and

monitor with serial duplex B. Referral for immediate carotid artery stent (CAS) with

embolic protection device C. Referral for immediate carotid endarterectomy (CEA) D. Continue current medical therapy with serial duplex

exams

Stroke: By the Numbers

800,000 strokes/year in the United States Approximately 80% are ischemic, 20% hemorrhagic 8-10% of ischemic strokes are attributed to carotid

stenosis; mechanism is plaque rupture and embolism In the year 2012, in the United States we performed:

~8,000 carotid artery stent (CAS) procedures 140,000 carotid endarterectomy (CEA) procedures

CEA is one of the most common procedures performed in vascular surgeons’ daily practice

Asymptomatic Carotid Stenosis

By age 75, about 7% of the population will have some degree of asymptomatic stenosis

In the Medicare population over age 65, 1-2% will have high grade asymptomatic carotid stenosis

Management of these patients is controversial, based in part on variable or small benefits for revascularization in randomized trials and improvements in medical therapy since pivotal trials have been published

What would NEJM readers do?

WHY THE CONTROVERSY?

Common problem; common procedure, so…..

ACAS and ACST: Pivotal Trials

ACAS and ACST Results: 5 year Outcomes

ACAS and ACST: Issues

Medical therapy arm had essentially no therapy: statins, BP control, antiplatelet therapy

Surgical sites were highly selected: best outcomes (3% stroke risk during surgery)

Population studied: Men!!

Sooooo- the best surgeons compared to the worst medical therapy had a very small benefit, maybe none in women?

Are we sure about this??

Annual Stroke Risk for Asymptomatic Disease

Medical Therapy: A Moving Target

Changes in Stroke Risk over Time

Statin Use in ACST

Lancet 2010;376:1074

Effect of Statin Use on Outcomes

The writing is on the board: Statins work!

Guidelines: 2011 Update for Asymptomatic

Class I

Class IIA

Guidelines: 2011 Update for Asymptomatic

Class IIb

How to Pick?

Management of Asymptomatic Stenosis

Clinical Question #1

A 67 yo male is seen in clinic follow up. He has an asymptomatic left carotid bruit and a duplex demonstrates a 50-79% stenosis of the left internal carotid artery. He has known CAD and hyperlipidemia and is on aspirin and atorvastatin. He has a normal creatinine. The one year risk for an ipsilateral stroke is:

A. 1% B. 3% C. 5-7% D. >10%

Clinical Question #2

The patient in question #2 wants the best therapy possible for his carotid stenosis, telling you “I don’t want a stroke.” You recommend:

A. . Add clopidogrel (Plavix) to his medications and

monitor with serial duplex B. Referral for immediate carotid artery stent (CAS) with

embolic protection device C. Referral for immediate carotid endarterectomy (CEA) D. Continue current medical therapy with serial duplex

exams

Part 2: Symptomatic Carotid Stenosis

Clinical Question

A 67 y.o. male presents with right eye amaurosis fugax lasting for 5 minutes three days ago. His symptoms resolved spontaneously and he underwent duplex scanning of the carotid arteries, revealing an 80% RICA stenosis with some “plaque ulceration.” He has known paroxsymal atrial fibrillation, hypertension, and lower extremity PAD. His medications include aspirin, lisinopril, atorvastatin, and coumadin. INR is 1.9. Best next therapy is: A. Add clopidogrel (Plavix) to medications and monitor B. Refer for immediate CEA C. Refer for immediate CAS D. TEE E. Double statin dose and repeat duplex in 3 months

Symptomatic Carotid disease

Clinical symptoms are related to hemispheric stroke/TIA from an unstable carotid plaque

Symptoms occurred within the previous 6 months Pivotal Trials which have shaped guidelines are: NASCET (North American Symptomatic Carotid

Endarterectomy Trial) published 1991 in NEJM ECST (European Carotid Surgery Trial) published in Lancet in

1998

Outcomes: ECST and NASCET

Determining Stenosis Severity in Trials

ECST and NASCET had different stenosis determination

ECST 80%= NASCET 60%

Relationship Between % Stenosis and Stroke

70-95% stenosis

95-99%

Relationship between % Stenosis, Age, Stroke

Relationship between Plaque Ulceration and Stroke

Timing of Surgery

CEA in Symptomatic Disease

In trials, surgical stroke risk with CEA is ~6% in experienced hands

Most data supports early revascularization (within 2-4 weeks of index event) owing to high risk of recurrent TIA/stroke with waiting, particularly in those with higher grade lesions

Women (again) underrepresented but did have benefit, although not as great as men

Elderly benefit

Guidelines

Clinical Question

A 67 y.o. male presents with right eye amaurosis fugax lasting for 5 minutes three days ago. His symptoms resolved spontaneously and he underwent duplex scanning of the carotid arteries, revealing an 80% RICA stenosis with some “plaque ulceration.” He has known paroxsymal atrial fibrillation, hypertension, and lower extremity PAD. His medications include aspirin, lisinopril, atorvastatin, and coumadin. INR is 1.9. Best next therapy is: A. Add clopidogrel (Plavix) to medications and monitor B. Refer for immediate CEA C. Refer for immediate CAS D. TEE E. Double statin dose and repeat duplex in 3 months

STENTING (CAS) OR SURGERY (CEA)FOR CAROTID

REVASCULARIZATION

Part 3

The Data: CAS and CEA

CREST Trial

Methods

Randomized, controlled trial with blinded end-point

117 centers in US and Canada (108 US) Proceduralists in study were certified to enroll

patients if: >12 procedures/year Rates of complications and death < 3% among

asymptomatic pts and <6% among symptomatic pts.

Methods - Patient Selection

Symptomatic = TIA, amaurosis fugax, or minor disabling stroke involving study carotid w/in 180 days before randomization.

Eligibility: 50%+ on angiography 70%+ on u/s, CTA, MRA In 2005, included asymptomatic pts with:

60+% on angiography 70+% on u/s 80+% on CTA or MRI if u/s showed 50-69%.

Methods - Patient Selection

Exclusion criteria: Previous CVA Atrial fibrillation w/in preceding 6 months MI within previous 30 days UA Anatomical reasons

CAS & CEA

CAS Involved RX Acculink stent, when feasible RX Accunet

embolic protection device Pretreatment with ASA 325mg BID, Clopidogrel 75mg

QD, at least 48 hrs prior to CAS If CAS scheduled within 48hrs of randomization, ASA

650mg and Clopidogrel 450mg given 4 or more hours before procedure

Post-CAS: ASA 325mg or 650mg dail + Clopidogrel 75 or Ticlopidine 250mg BID x 4 weeks.+

CAS & CEA

CEA 48+ hrs prior, ASA 325mg daily for 1 year or more (or

ticlopidine 250mg BID or Clopidogrel 75mg daily, ASA 81mg daily, Dipyridamole BID)

F/U Assessment of End-Points

Neuro evaluation at baseline, 18-54 hrs post-procedure, 1 month, q6 months thereafter.

Cardiac biomarkers measured pre-procedure, 6-8 hrs after, 1 month.

ECG before CAS/CEA, 6-48hrs after, 1 month after.

Carotid u/s before CAS/CEA, 1, 6, and 12 months, and annually thereafter

Phone f/u at 3 months and 6 months thereafter

Endpoints

Primary end-point: CVA, MI, or death during periprocedural period or ipsilateral CVA within 4 years after randomization.

N=2502

Results - Primary End Point

Results

Stroke more common after CAS MI more common after CEA Overall composite endpoint showed no statistical

difference

Primary End Point (4yr)

Primary End Point by Age

Results

Primary end point did NOT differ among symptomatic or asymptomatic pts.

Peri-procedural cranial-nerve palsies less frequent among CAS patients.

4-yr CVA or death 6.4% (CAS) vs 4.7% in CEA (p=0.03). Symptomatic pts: 8% vs 6.4% (p=0.14) Asymptomatic pts: 4.5% vs 2.7% (p=0.07)

Post-hoc Analyses

Major/minor CVA found to have effect on physical health at 1 year; periprocedural MI less clear.

Minor CVA had significant effect on mental health at 1 year

Likelihood of primary end point not significantly affected by the specialty of the interventionist performing CAS (p=0.51).

CREST 10 Year Data (published 2016)

Brott et al. Long term results of stenting versus endarterectomy for

carotid stenosis. NEJM, 374(11), 2016.

ACT 1

Limitations

Overall, a very well conducted study!

Highly trained proceduralists - may be more than the average in practice.

One stent platform used. Medical Rx not specifically tested.

Summary - CREST

CAS and CEA associated with similar combined rates of periprocedural CVA, MI, or death and subsequent ipsilateral CVA (symptomatic and asymptomatic men and women).

Incidence of periprocedural stroke lower in CEA cohort; incidence of MI lower in CAS cohort.

Younger pts had slightly fewer events after CAS; older pts had fewer events after CEA.

Medical therapy similar in both groups

( T I M E T O W A K E U P )

Overall Conclusions

Conclusions and Summary

Asymptomatic carotid stenosis is common, and for many patients medical therapy is all that is needed

Selected patients with good life expectancy and moderately high grade stenosis (in the hands of good surgeons) may be appropriate for CEA

Controversy exists over how to select the best asymptomatic patients for carotid revascularization.

Conclusions and Summary

Symptomatic patients with high grade stenosis should be considered for CEA or CAS

CAS and CEA should be considered as similar procedures, with the choice of procedure dependent on patient factors and local expertise

Medical therapy is crucial in the management of any carotid stenosis, regardless of symptoms

Unknown how modern medical therapy fares against revascularization for symptomatic patients- stayed tuned!

Hopefully not too vague!!

T H A N K Y O U

J A M E S . D E V R I E S @ H I T C H C O C K . O R G