CAROTID ARTERY DISEASE

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CAROTID ARTERY DISEASE

• Jehanzeb Bilal, MD
• PGY-3
• Elias A. Iliadis, MD
• Medical Director, Noninvasive Vascular
  Intervention
• Cooper Heart Institute

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Patient one

• 49 year old female presents to her primary care
  physician for a routine check up.
• PMH unremarkable.
• Social hx smoker (1PP-30yrs).
• Family History CAD, HTN, CVA

3

• VS.97 125/75 65 12
• Neurological exam normal.
• Cardiovascular right carotid bruit.
• The rest of the exam was unremarkable
• A carotid ultrasound was done.

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• The ultrasound revealed a 95 stenosis of the
  left carotid.

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• Would you screen for carotid disease in
  asymptomatic patients?
• What is the value of a carotid bruit on physical
  exam in an asymptomatic patient?
• What is a hemodynamically significant carotid
  stenosis?
• Would you further evaluate this patient ?
• How would you manage her carotid stenosis?

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The Framingham cohort

• Evaluation of carotid bruit in this cohort
• In eight years, a bruit appeared in 66 men and
• 105 women, all asymptomatic.
• The incidence increased with age equally in the
  two sexes from 3.5 at 44 to 54 years, to 7.0 at
  65 to 79 years.
• The eight-year incidence was greater in diabetes
  and hypertensive subjects.
• These patients had a stroke rate more than twice
  expected for age and sex.
• JAMA 1981 Apr
  10245(14)1442-5.

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• More often cerebral infarction occurred in a
  vascular territory different from that of the
  carotid bruit
• Ruptured aneurysm, embolism from the heart, and
  lacunar infarction was the mechanism of stroke in
  nearly half the cases.
• Incidence of myocardial infarction increased
  twofold .
• General mortality increased 1.7-fold with men,
  and 1.9-fold in women, with 79 of the deaths
  owing to cardiovascular disease, including
  stroke.

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Conclusion of the study

• Carotid bruit is clearly an indicator of
  increased stroke risk
• General and non-focal sign of advanced
  atherosclerotic disease
• Not necessarily an indicator of local arterial
  stenosis preceding cerebral infarction

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The natural history of asymptomatic carotid
artery occlusive lesions.

•  
• Follow up of 640 neurologically asymptomatic
  patients
• 292 had pressure-significant internal carotid
  artery stenosis
• 348 had a carotid bruit only without a
  pressure-significant lesion.
• Patients with asymptomatic pressure-significant
  carotid stenosis are at greater risk for stroke
  than a non significant occlusion (twofold) and a
  general population (sevenfold).
• 
  JAMA 1987Nov20258(19)2704-7

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The natural h/o carotid bruits in the elderly

• To determine the relative risk for
  cerebrovascular events in elderly patients with
  carotid bruits
• 241 NH residents were examined for carotid bruits
  and signs of previous stroke.
• Twelve percent of residents had asymptomatic
  carotid bruits.
• The 3-year cumulative incidence of strokes was
  10, vs. 9, yielding a relative risk of 1.1 (95
  CI, 0.45 to 2.7).
• In 60 of surviving residents, baseline carotid
  bruits were no longer present at the time of
  follow-up examination.
• The disappearance of these bruits was not
  associated with the occurrence of interval
  cerebrovascular events
• Ann Intern
  Med1990Mar12(5)340-3

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SHEP

• The Systolic Hypertension in the Elderly Program
• To determine the association between asymptomatic
  carotid bruits and the development of subsequent
  stroke in older adults with isolated systolic
  hypertension.
• 5-year randomized trial
• Average follow-up 4.2 years.
• Carotid bruits were found in (6.4) of the
  participants .
• Stroke developed in (7.4) of those with carotid
  bruits and in (5.0) of those without carotid
  bruits.
• J Gen Intern Med 1998
  Feb13(2)86-90

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• Relative risk of stroke with asymptomatic carotid
  bruits was 1.29 (95 CI 0.80, 2.06).
• Subjects aged 60 to 69 years, trend (p.08)
  toward increased risk (relative risk RR 2.05
  95 CI 0.92, 4.68) of subsequent stroke in
  persons with carotid bruits.
• Subjects aged 70 or over, no relation between
  carotid bruit and subsequent stroke (RR 0.98 95
  CI 0.55, 1.76).

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The causes and risk of stroke in patient with
internal carotid artery stenosis

• patients with unilateral symptomatic
  carotid-artery stenosis
• Patients with asymptomatic contralateral stenosis
• The risk of stroke at five years after study
  entry in a total of 1820 patients increased with
  the severity of stenosis.
• N Engl J Med 2000 3431420-1421,
  Nov 9, 2000.

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

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EVALUATION OF CAROTID DISEASE
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Conventional angiography

• Gold standard
• Visualize the entire cerebrovascular system
• Invasive test
• Expensive test
• Neurological morbidity/mortality

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Non invasive carotid artery testing. A
meta-analytic review.

• Carotid angiography as the reference standard for
  comparison.
• Carotid duplex ultrasonography, carotid Doppler
  ultrasonography, and magnetic resonance
  angiography are all similarly successful at
  predicting
• -100 carotid artery occlusion (SN 82 to 86,SP
  98)
• -70 stenosis (SN 83 to 86,SP 89 TO 94 )
• Other factors, such as cost, availability, and
  local experience may influence the decision to
  use these tests to screen for carotid artery
  atherosclerosis that may respond to surgery
• Ann Intern Med 1995 Mar
  1122(5)360-7.

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Ann Int Med 1995,122,P360.
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Duplex ultrasound and magnetic resonance
angiography compared with digital subtraction
angiography in carotid artery stenosis a
systematic review

• 64 studies reviewed.
• MRA has a better discriminatory power compared
  with DUS in diagnosing 70 to 99
  stenosis(SN95vs86/SP90vs87)
• A sensitive and specific test compared with DSA
  in the evaluation of carotid artery stenosis.
• For detecting occlusion, both DUS and MRA are
  very accurate.(SN 98 vs. 96/SP 100VS 100)
• Stroke
  2003 May34(5)1324-32.  

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Non-invasive imaging compared with intra-arterial
angiography in the diagnosis of symptomatic
carotid stenosis a meta-analysis

• CEMRA is superior to US,MRA and CTA, with SN 94
  versus 89, 88, and 76 percent, respectively
  specificities 93 versus 84, 84, and 94 percent,
  respectively
• Lancet. 2006 May
  6367(9521)1503-12

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Carotid US

• Least expensive
• Easy to perform
• Defines the plaque
• -The sensitivity and specificity are lower in
  asymptomatic patients
• -It can overestimate the stenosis unnecessary
  surgery
• -Less precise in less than 50 stenosis, and
  total occlusion
• -It only defines cervical disease

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MRA

• May be more Sensitive and Specific than US (esp.
  CEMRA)
• Disadvantage
• -Cannot be done if patient is critically ill , or
  has a pacemaker
• -Expensive

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CTA

• Used when US is not reliable
• -Severe calcific artery
• -Severe kinking of the vessels
• -Short neck
• -High bifurcation
• -Overview of surgical field

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Can we bypass invasive angiography?

• Separate and combined test results of DUS and MRA
  were compared with the reference standard DSA.
  Only the stenosis measurements of the arteries on
  the symptomatic side were included in the
  analyses.
• When MRA and DUS were combined , agreement
  between these 2 modalities (84 of patients) gave
  a sensitivity of 96.3 (95 CI, 90.8 to 99.0)
  and a specificity of 80.2 (95 CI, 73.1 to
  87.3) for identifying severe stenosis(gt70)
• This combination may obviate the need of an
  invasive angiography ,if the results of both
  tests were similar.
• Stroke
  2002 Aug33(8)2003-8.

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Guidelines

• The United States Preventive Services Task Force
  (USPSTF) recommends against screening for
  asymptomatic carotid artery stenosis in the
  general population .
• The American Heart Association and American
  Stroke Association acknowledge that "screening of
  general populations for asymptomatic carotid
  stenosis is unlikely to be cost-effective" .
• The American Society of Neuroimaging suggests
  that, while screening for the general population
  is not recommended, screening might be considered
  for patients 65 years with significant risk
  factors for cardiovascular disease .

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PREVENTION OF STROKES IN ASYMPTOMATIC BUT
HEMODYNAMICALLY SIGNIFICANT CAROTID ARTERY
STENOSIS.
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VA STUDY

• Multicenter clinical trial
• 444 men with asymptomatic carotid stenosis shown
  arteriographically (50 percent or more).
• Randomly assigned to optimal medical treatment
  including ASPIRIN plus carotid endarterectomy (
  211 patients) or optimal medical treatment alone
  (233 patients)
• The incidence of ipsilateral neurologic events
  was 8.0 percent in the surgical group and 20.6
  percent in the medical group (P 0.001), RR of
  0.38 (95 confidence interval,( 0.22 to 0.67).
• N Engl J Med 1993
  Jan 28328(4)221-7

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ACAS(asymptomatic carotid atherosclerosis study)

• Randomized, multicenter trial
• Total of 1662 patients with asymptomatic carotid
  artery stenosis of 60 or greater
• medical risk factor management for all patients
  carotid endarterectomy for patients randomized to
  receive surgery.
• After a median follow-up of 2.7 years, the
  incidence of ipsilateral stroke and any
  perioperative stroke or death rate was
  significantly lower in the surgical group than
  with aspirin alone (5 versus 11 percent) for a
  relative risk reduction of 0.53 (95 CI
  0.22-0.72).
• Men had an absolute risk reduction of 8 percent
  the absolute risk reduction in women was only 1.4
  percent.
• 
  JAMA 1995 May 10273(18)1421-8

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ACST (asymptomatic carotid surgery trial)

• 3120 asymptomatic patients with 60 stenosis(US)
• randomized between immediate CEA and indefinite
  deferral of any CEA (4 per year)and were
  followed for up to 5 years.
• The net five-year risk for all strokes or
  perioperative death in the CEA group was reduced
  by nearly half.
• The absolute risk reduction over five years was
  greater for men than for women 8.2 percent
  versus 4.08
• Lancet
  2004 May 8363(9420)1491-502.

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COCHRANE REVIEW

• All completed randomized trials comparing CEA to
  medical treatment in patients with asymptomatic
  carotid stenosis
• 5223 patients were included.
• Despite about a 3 perioperative stroke or death
  rate, CEA for asymptomatic carotid stenosis
  reduces the risk of ipsilateral stroke, and any
  stroke, by approximately 30 over three years.
• The absolute risk reduction is small
  (approximately 1 per year over the first few
  years of follow up in the two largest and most
  recent trials) but it could be higher with longer
  follow up.
• Cochrane Database Syst Rev
  2005(4)CD001923

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Factors to consider in assessing risk and
benefit of CEA

• Exclusion criteria (life expectancy of lt five
  years)
• The severity of stenosis.
• The presence of newer drugs.
• The frequency of TIA in carotid disease.

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• The differentiation between the nature of
  stroke(cardioembolic and lacunar).
• The controlateral carotid artery.
• The Late benefit of CEA.
• The gender.
• Postoperative complications.

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Guidelines

• For asymptomatic patient with a stenosis of 60
  to 99 ,CEA is recommended only for patients
  aged between 45 and 75 with a life expectance of
  at least five years. NNT 33
• The benefit of CEA appears only after couple of
  year.
• ASA should be used pre and postoperatively.

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Patient two

• 69 y old female was found to have b/l carotid
  bruit on physical exam. She has no history of
  strokes or transient ischemic attack.
• PMH CAD with triple vessel disease , CHF with
  diastolic dysfunction, DM, HTN, dyslipidemia.
• She is a past smoker(40 p/year)
• Meds coreg, simvastatin, lisinopril, insulin,
  asa, lasix.

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• A carotid ultrasound and a conventional
  angiography showed a severe stenosis(more than
  95) of her right ICA ,
• Is she a candidate for a CEA? What is the current
  data on Carotid Artery Stenting?

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SAPHIRE(stenting and angioplasty with protection
in patients at high risk of endarterectomy

• A randomized trial comparing carotid-artery
  stenting with the use of an emboli-protection
  device to endarterectomy
• 334 patients with coexisting conditions that
  potentially increased the risk posed by
  endarterectomy and who had either a symptomatic
  carotid-artery stenosis of at least 50 percent of
  the luminal diameter or an asymptomatic stenosis
  of at least 80 percent.
• More than seventy percent of patients had
  asymptomatic disease.
• Twenty percent had a restenosis after CEA.
• N Engl J Med 2004 Oct
  7351(15)1493-501.  

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• The primary end point was a combined incidence
  of death, stroke and MI in the first thirty days
  postoperatively or death/ipsilateral stroke from
  day 31 up to one year.
• The study was designed to test the
  non-inferiority of CAS to CEA in this population.

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• The primary end point occurred in 20 patients
  randomly assigned to undergo carotid artery
  stenting and in 32 patients randomly assigned
  to undergo endarterectomy (P0.004 for
  noninferiority, and P0.053 for superiority).
• At one year, carotid revascularization was
  repeated in fewer patients who had received
  stents than in those who had undergone
  endarterectomy (P0.04).
• CAS is non inferior to CEA in patient with
  carotid artery disease and high risk for surgery.

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• The FDA approved the stent used in this trial for
  high risk patients with carotid disease.

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Guidelines

• CAS should be considered in patients with severe
  carotid stenosis(gt70) and one of the following
  conditions
• -Severe medical comorbidities(cardiopulmonary).
• -Difficult neck access for CEA.
• -Stenosis after irradiation.
• -Restenosis after CEA.
• -Contralateral laryngeal palsy.

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Patient three

• 57 year old male presents to the ER with acute
  weakness of his right arm and leg .The symptoms
  started 12 hour ago.
• He has a h/o of HTN and dyslipidemia, currently
  on lisinopril and simvastatin.
• Physical exam97 170/100 85 15
• -He had a 4/5 weakness of his right arm and leg
• -Cardiovascular exam was unremarkable

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• CT scan of the brain without contrast showed
  chronic small vessel disease.
• MRI brain revealed an acute infarct of left
  middle cerebral artery territory.
• MRA showed an 90 stenosis of his left carotid
  artery.
• He was admitted to the stroke unit.

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Is the management of carotid disease different
in symptomatic patients?
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NASCET TRIAL(North American Symptomatic Carotid
Endarterectomy Trial)

• 659 patients with a h/o of stroke in the past 120
  days
• had 70-90 stenosis of the ipsilateral carotid
  artery.
• Patients were randomized to medical management
  vs. medical management with CEA.
• The primary outcome was any stroke or death.
• The study was prematurely terminated by the NIH
  because of the clear evidence of benefit from
  surgery .
• At the time of study termination, patients had
  been followed for a mean of 18 months.
• N Engl J Med 1991 Aug
  15325(7)445-53

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• The risk of stroke and death was higher at 30
  days in the patients treated with CEA (5.8 versus
  3.3 percent with medical therapy)
• longer follow-up revealed a lower cumulative
  risk at two years of any ipsilateral stroke (9
  versus 26 percent, plt0.001)
• A lower risk of major or fatal ipsilateral stroke
  (2.5 versus 13.1 percent, plt0.001)

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• CEA was highly beneficial (9 vs. 26 ,plt0.001)for
  patients with recent TIAs or nondisabling strokes
  with ipsilateral stenosis of 70 to 99
• moderate degree of benefit for patients with 50
  to 69 percent symptomatic ipsilateral stenosis (
  15.7 versus 22.2) percent (p 0.045)
• Patients with stenosis of less than 50 percent
  did not benefit from surgery.
• Elderly patients with 50 to 99 percent stenosis
  benefited more from CEA than younger patients
• These findings suggest that CEA should not be
  withheld from appropriately selected, fit
  patients over the age of 75.

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ECST(European carotid surgery trial)

•  A multicentre trial of 3024 patients
• randomized to carotid endarterectomy and
  medical management vs. medical management alone
• All patients had a recent stroke or TIA in a
  carotid artery distribution, and some degree of
  carotid stenosis.
• Median follow up was for six years.
• Lancet 1998 May
  9351(9113)1379-87

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• The risk of major ischemic stroke ipsilateral to
  the unoperated symptomatic carotid artery
  increased with severity of stenosis, particularly
  above about 70-80 of the original luminal
  diameter, but only for 2-3 years after
  randomization.
• On average, the immediate risk of surgery
  (7)was worth trading off against the long-term
  risk of stroke without surgery when the stenosis
  was greater than about 80 diameter.
• For disabling or fatal stroke the control risks
  seemed to diminish after the first year, so delay
  of surgery by just a few months after clinical
  presentation might make this overall difference
  non-significant.  

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SPACE TRIAL(stent-protected angioplasty versus
carotid endarterectomy )

• 1200 patients with symptomatic carotid-artery
  stenosis within 180 days of enrollment
• Patients were randomly assigned carotid-artery
  stenting (n605) or carotid endarterectomy
  (n595).
• The primary endpoint was ipsilateral ischemic
  stroke or death from time of randomization to 30
  days after the procedure.
• Non inferiority study.
• Lancet. 2006 Oct
  7368(9543)1239-47

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• The trial was stopped after the second interim
  analysis, mainly due to recruitment and funding
  problems.
• SPACE failed to prove the non-inferiority of
  carotid-artery stenting compared with carotid
  endarterectomy
• expressed as the rate of ipsilateral stroke or
  death within 30 days after treatment in
  symptomatic patients with moderate to severe
  stenosis of the carotid artery.
• The use of embolic protection devices with
  stenting was optional, and were used in only 27
  percent of patients treated with CAS.

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EVA-S trial(Endarterectomy vs. angioplasty with
stenting)

• Multicenter, randomized, noninferiority trial to
  compare stenting with endarterectomy in patients
  with a symptomatic carotid stenosis of at least
  60.
• The primary end point was the incidence of any
  stroke or death within 30 days and six months
  after therapy .
• N Engl J Med. 2006 Oct
  19355(16)1660-71

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• The trial was stopped prematurely after the
  inclusion of 527 patient because of worse outcome
  with the CAS branch.
• The 30-day incidence of any stroke or death was
  3.9 after endarterectomy (95 confidence
  interval CI, 2.0 to 7.2) and 9.6 after
  stenting (95 CI, 6.4 to 14.0)
• At 6 months, the incidence of any stroke or death
  was 6.1 after endarterectomy and 11.7 after
  stenting (P 0.02).

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• Critics
• Lack of experience by many of the
  interventionalists doing the CAS.
• Five different stents and seven different
  cerebral protection devices were used in EVA-3S
• interventional clinicians were required to have
  performed only two stenting procedures with any
  new device before its use in the trial.
• Embolic protection for patients assigned to CAS
  was optional early in the trial, and the 30-day
  outcome of any stroke or death was significantly
  lower in patients treated with (n 277) than in
  those treated without (n 20) embolic protection
  (7.9 and 25 percent, respectively).

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Guidelines

• For symptomatic carotid artery stenosis of 70 to
  99 with no severe co-morbidities CEA .NNT of
  6.3.
• For symptomatic stenosis of 50 to 69CEA. NNT of
  22.
• ASA should be started before surgery and
  continued postoperatively.

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Conditions associated with less or no benefit
from CEA

• Severe disabling strokes
• Transient monocular ischemia VS hemispheric TIA
• Younger population
• Total carotid stenosis
• Controlateral carotid stenosis increase
  perioperative risk

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Complication of Carotid artery stenting

• Stroke.
• Periprocedural bradycardia and hypotension
• Technical difficulty.
• Restenosis(early 0.5 to 2,late 0.6 to 6)
• Hyperperfusion syndrome.

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Thank you