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Asymptomatic Carotid StenosisAsymptomatic Carotid Stenosis

Munier Nazzal, MD, FRCS, FACS, FACCWSProfessor, General Surgery Program Director

Chief Division, Vascular &Endovascular SurgeryUniversity of Toledo, OH, USA

Stroke , 2014, Toledo, Ohio

Dislcosure Investigator in SAPPHIRE

Speaker for Medtronic, argon

PI in CREST, and Oxford.

Case  65 year , male patient.

DM, HTN, CAD

Bilateral carotid stenosis :  left (60%) symptomatic : CEA.  Right side has 65% asymptomatic : Conservative therapy

Discharge home after surgery and followed up in the clinic for three months/ During this time he was always asking to do CEA for the right side:  convinced not to.

2 months later admitted with right hemispheric stroke and then rehab

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Prevalence of ACAS

Carotid disease : Facts 87% of all CEA are in asymptomatic patients.

Carotid stenosis is a a marker for CVS and for cardiac death.

Women do not benefit as much as men from CEA or CAS.

Both CEA and CAS are  not as safe in older patients.

More than 60% of the cases or CEA are done in patients older than 70 years.

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Asymptomatic CAS studies

Schneider etal., 2010

Randomized Trials

Asymptomatic Carotid StenosisAsymptomatic Carotid Stenosis

5 Year Risk of Cerebral Events

ACAS ACST

BMT CEA ARR BMT CEA ARR

Ipsilat Stroke 11.0% 5.1% 5.9% 5.1% 4.4% 1.1%

Any Stroke 17.5% 12.4% 5.1% 11.8% 6.4% 5.4%

Major Stroke 9.1% 6.4% 2.7% 6.1% 3.5% 2.6%

Naylor A R et alEJVES 2009.01.026 (epub 4/09)

Cutlip et al, circulation 2012

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Asymptomatic Carotid DiseaseAsymptomatic Carotid Disease

procedural risk - 2.3%

Prevent almost 60 stroke (ipsilateral ) in 1000 patients compared to Medical therapy done in the 

80’s  and 90’s

procedural risk - 2.3%

Prevent almost 60 stroke (ipsilateral ) in 1000 patients compared to Medical therapy done in the 

80’s  and 90’s

ACASJAMA 1995; 273:1421

Asymptomatic Carotid Disease

Asymptomatic Carotid Disease

…To operate on all patients with more than 60% stenosis will prevent about 5% of all strokes according to the literature

…To operate on all patients with more than 60% stenosis will prevent about 5% of all strokes according to the literature

Naylor A RSurgeon 2007; 5:23

Hankey G JMed J Aust 1995; 163:197

Stroke 2013

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293 (6.8%) patients with ACAS 50% to 99%, of whom 193 had 70% to 99% stenosis. mean follow‐up was 6.2 and 6.0 years, respectively. 

Any territory annual ischemic stroke risk was 0.4% in 50% to 99% ACAS and 0.5% per year for 70% to 99% ACAS patients. 

The risk of ischemic stroke was not significantly increased in patients with ACAS 70% to 99% 0.5–4.2 and hazard ratio, 1.7; 95% confidence interval, 0.5–5.6).

Challenges

Medical care ????  Best medical therapy not well defined.

Statins

Antiplatelets.

Hypertension control

Smoking cessation

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Asymptomatic  Not all asymptomatic behave the same.

Age : is a factor

Comorbidities

Asymptomatic Carotid Disease

The best results for asymptomatic carotid stenosis came from the following two studies

Asymptomatic Carotid Atherosclerosis Study (ACAS) 

Asymptomatic Carotid Surgery Trial (ACST)

Most feared:Stroke

Most frequent : Myocardial infarction

death

only one third to one half of these strokes were ischemic and ipsilateral and could be attributed to the carotid stenosis, others have other reasons

Forty‐five percent of strokes in patients with asymptomatic stenosis of 60 to 99 percent are attributable to lacunes or cardioembolism

Inzitari et al, NEJM 2000

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Carotid Endarterectomy in the USA

Procedural Risk (Stroke/Death) ‐ 3.8%

“? Real‐World Results”

• 44 ipsilateral strokes prevented per 1000 procedures at 5 years

• 5,411 strokes prevented from 122,986 procedures

• $428,510 per stroke prevented

Procedural Risk (Stroke/Death) ‐ 3.8%

“? Real‐World Results”

• 44 ipsilateral strokes prevented per 1000 procedures at 5 years

• 5,411 strokes prevented from 122,986 procedures

• $428,510 per stroke prevented

Kresowik T FJ Vasc Surg 2004; 39:372

1. Calhoun HMLancet 2004; 364: 685

2. MRC/BHF HPS Investigators,Lancet 2002; 360:7

1. Calhoun HMLancet 2004; 364: 685

2. MRC/BHF HPS Investigators,Lancet 2002; 360:7

25%25%5.0 yrs 5.0 yrs High Risk2High Risk2

46%46%3.9 yrs 3.9 yrs Diabetics1Diabetics1

RRRRRRF/UF/UPatientsPatients

Statins vs. Placebo

Statins and Risk of StrokeStatins and Risk of Stroke

Results at 4.9 yearsResults at 4.9 years

SPARCL InvestigatorsNEJM 2006;355:549

EndpointEndpoint RRRRRR P‐valueP‐value

• 4731 stroke / TIA patients

• Randomized: atorvastatin 80mg vs. placebo

• 4731 stroke / TIA patients

• Randomized: atorvastatin 80mg vs. placebo

Stroke (any)Stroke (any)

Stroke/TIAStroke/TIA

Any CV eventAny CV event

Major CV eventMajor CV event

16%16%

35%35%

26%26%

23%23%

.03.03

<.001<.001

<.001<.001

<.001<.001

Risk Reduction with StatinSPARCL TrialSPARCL Trial

SPARCL study

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• Prospective

• 2684 consecutive patients– Clinical manifestations of arterial disease, or– Type II diabetes

• No history of cerebral ischemia

• Carotid duplex

• 221 (8%) ≥50% carotid stenosis

• Follow‐up to 5 years (mean 3.6 years)

• Evaluated for ischemic events

• Prospective

• 2684 consecutive patients– Clinical manifestations of arterial disease, or– Type II diabetes

• No history of cerebral ischemia

• Carotid duplex

• 221 (8%) ≥50% carotid stenosis

• Follow‐up to 5 years (mean 3.6 years)

• Evaluated for ischemic events

Second Manifestation of ARTerial DiseaseSecond Manifestation of ARTerial Disease

The SMART Study(2007)

The SMART Study(2007)

Bertine M B et alStroke 2007; 38:1470

Annual risk of “ipsilateral” or “any” stroke from 

50 ‐ 99% stenosis was <1%

Annual risk of “ipsilateral” or “any” stroke from 

50 ‐ 99% stenosis was <1%

SMART Study

Asymptomatic Carotid DiseaseAsymptomatic Carotid Disease

Goessens B M B et alStroke 2007; 38:1470

Annual risk of “ipsilateral” or “any” stroke from 

50 ‐ 99% stenosis was <1%

Can Medical Therapy Control ACAS

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Medically managed patients with ASCAS develop INS early, especially in patients with VSS. Medical therapy with aspirin and statins failed to control ASCAS, thus validating the role of CEA in these patients as promulgated in multiple current treatment guidelines.

JVS 2014

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JVS, 2010

Factors evaluated:Age, gender, BMI, SBP, DBP, smokingMedications: antiplatelets, HTN, lipids.HTN, CAD, DM, stroke/TIA of other carotid side.ECG of a‐fib, MI, ischemic LVHFibrinogen, lipids levels, S‐creat, Hct,

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In press, JVS

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Conclusions of the Study Progressive asymptomatic carotid stenosis identified a 

subgroup with about twice the risk of ipsilateral stroke compared with those without progression. 

The clinical value of screening for progression simply for selecting patients for carotid procedures is limited because of the low frequency of progression and its relatively low associated stroke rate. 

The cost effectiveness of screening for change in stenosis severity to better direct current optimal medical treatment needs testing.

Kakkos et al, JVS 2014

Characteristic Asymptomatic (n = 1181)

Symptomatic (n = 1321) P

Age, years (mean ± SD) 69.3 ± 8.1 68.8 ± 9.5 <0.17

Male, % 65.6 64.7 0.64

Hypertension, % 88.0 84.0 0.004

Diabetes, % 33.2 28.1 0.006

Dyslipidemia, % 90.4 79.0 <0.0001

Current smoker, % 24.1 28.2 0.02

Stroke. 2011;42:875-880

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4 year event rate for stroke, MI, and death (%)

Stroke. 2011;42:875-880

Lancet. 2014;383:333-341

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High Grade Stenosis

Look for ContraindicationsFor Surgery

Randomize

Surgeon OR Interventionist

Look for ContraindicationsFor Stenting

Decide Type of Revasc best for patient

• Preoperative• Aspirin + statin load (CEA) and• Dual antiplatelets + statin load (CAS)

• Patients in both trials will take aspirin 325 mg/day for the entire follow-up period

• CAS patients will also take clopidogrel per protocol

• Primary risk factor control managed by the study physician. Focused on:• Target systolic blood pressure <140 mmHg• Target LDL <70 mg/dl

• Is the change of cognitive function from

baseline to 48 months no worse among those

in the MEDICAL cohort compared to the

CEA/CAS cohorts? (Cognitive function may be a

surrogate for TIA and/or asymptomatic brain injury).

• Computer-aided telephonic assessment by

team at University of Alabama at Birmingham.

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Asymptomatic carotid stenosis

Degree of stenosis

Age

Condition of Patients

Experience of the Operator