Vascular
General information
- Atherosclerotic plaques begin to form in the carotid artery at 20 yrs of age.
- In the extracranial cerebral circulation, plaques typically start on the back wall of the common carotid artery (CCA).
- As they enlarge, they encroach on the lumen of the ICA.
- Calcified hard plaques may not change with time.
- The risk of stroke correlates with
- Degree of stenosis
- Certain types of plaque morphology
- “Vulnerable” plaques:
- Atherosclerotic plaques likely to cause thrombotic complications, or those that tend to progress rapidly.
- Criteria for vulnerable plaques include: (Some of these features can be identified with high-resolution MRI)
- Intimal thickening
- Plaque fissure
- Lipid/necrotic core with thin fibrous cap
- Calcification
- Thrombus
- Intraplaque haemorrhage
- Outward remodelling
- Hypercoagulable states
- Blood viscosity
- Many patients with carotid stenosis face a greater risk of death due to MI than to stroke
Numbers
- Risk of stroke after TIA (NASCENT data)
- 26% over 2 years→carotid endarterectomy reduce risk 9%
- The estimated 30-day risk of stroke recurrence after first stroke is
- 3% at 30 days
- 26% at 5 years
- Stroke and death rate depending degree of carotid stenosis (five-year cummulative)
Near occlusion | 22 per 100 |
70% to 99% carotid stenosis | 29 per 100 |
50% to 69% carotid stenosis | 23 per 100 |
30% to 49% carotid stenosis | 21 per 100 |
<30% carotid stenosis | 14 per 100 |
- The rate of ipsilateral stroke in patients with asymptomatic carotid stenosis is much lower: possibly < 0.5% per year in patients with ≥ 50% stenosis treated with best medical therapy.
Presentation
- Carotid artery lesions are considered
- If there are one or more lateralizing ischemic episodes appropriate to the distribution of the lesion.
- Numbers
- If no CEA: 26% risk of stroke over 2 years for stenosis >50%
- 13% rate of stroke per year
- May present as
- TIA
- Stroke which lasts less than 24 hours
- RIND (Reversible ischemic neurologic deficit):
- Stroke which lasts more than 24 hours and settles within a week.
- Stroke with any of the following findings;
- Retinal insufficiency/infarction (central retinal artery is a branch of the ophthalmic artery): ipsilateral monocular blindness
- May be temporary:
- Amaurosis fugax, AKA transient monocular blindness (TMB).
- Four types:
- Type I: Embolic.
- Described “like a black curtain coming down” in one eye. Complete loss of vision, usually lasts 1–2 minutes
- Type II: flow related.
- Retinal hypoperfusion → desaturation of colour, usually described as a graying of vision
- Type III: vasospastic.
- May occur with migraines
- Type IV: miscellaneous.
- May occur with anticardiolipin antibodies
- Blindness may be permanent
- Middle cerebral artery symptoms:
- Contralateral motor or sensory TIA (arm and face worse than leg) with hyperreflexia and upgoing toe
- Language deficits if dominant hemisphere involved
- If the patient only has non-specific visual complaints, dizziness, or syncope not associated with TIA or stroke.
- The majority (80%) of carotid atherothrombotic strokes occur without warning symptoms.
- Usually discovered as a carotid bruit.
- Prevalence increases with age (2.3% in ages 45–54 yrs, 8.2% at ≥ 75).
- Accuracy of a bruit in predicting ICA stenosis: 50–83% (depending on cohort, criteria for stenosis…).
- Sensitivity is as low as 24%.
- Natural history
- Rare: Prevalence of carotid stenosis >50% in men and women> 65 years of age is 5–10%,
- With 1% having stenosis > 80%.
- Stroke risk of
- 0.5-1%/year for all degrees of stenosis
- 1.0-3.4% (2%)/2-3 year for 50–99% stenosis .
- Cumulative rates of ipsilateral stroke over
- 10 years (9.3%, or 0.9%/year)
- 15 years (16.6%, or 1.1%
- Higher risk with
- Progressing stenosis
- More severe stenosis.
- Asymptomatic carotid stenosis is an important marker of concomitant ischemic cardiac disease.
- In the REACH Study, patients with asymptomatic carotid stenosis (n = 3164) had statistically significantly higher age- and sex adjusted 1-year rates of transient ischemic attack, non-fatal stroke, fatal stroke, and cardiovascular death compared to patients without asymptomatic carotid stenosis (n = 30329).
Symptomatic:
Asymptomatic:
Evaluation of the extent of carotid disease
- Symptomatic patients will usually be assessed as part of a stroke/TIA protocol.
- Blds
- CBC with platelet count, fibrinogen, PT/PTT/INR (to R/O hypercoagulable state).
- Funduscopic exam may show Hollenhorst plaques (cholesterol crystal emboli) in the retina.
- Classification of patients based on the hemodynamics and also the embolic propensity of carotid lesions has thus far been too complex to be utilized in large studies.
- The tests described below place a great deal of emphasis on the greatest degree of stenosis, which is probably an oversimplification. Plaque composition and morphology is probably important.
Screening for asymptomatic carotid stenosis
- Recommendation
- US preventive services task force
- Do not screen for carotid stenosis in general
- Screen only for
- ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline 2011 USS duplex for
- Asymptomatic patients without clinical evidence of atherosclerosis who have 2 or more of the following risk factors
- HTN
- Diabetes
- Smoking
- FMHx
- 1st degree relative of atherosclerosis is before the age of 60
- Family history of ischaemic stroke
- Hypercholesterolemia
- Known cardiovascular disease
- Peripheral vascular disease
- Coronary artery disease
- Atherosclerotic aortic aneurysm
- Asymptomatic patient with carotid bruit
Test
Catheter arteriogram
- Gold standard test
- Cannot be justified as a screening test because
- Invasive
- Stroke risk 1%
- Costly
- Risky
- Recent data show<1% risk of transient or permanent deficit (risk is 2–3 times higher in symptomatic patients than in asymptomatic) in good hands.
- Unlike duplex Doppler and MRA, it does not provide any information about the thickness of the plaque.
- Different definitions of the degree of stenosis are employed;
- North American Symptomatic Carotid Endarterectomy Trial (NASCET) study vs European Carotid Surgery Trial (ECST)
- The studies differ in the denominator
- N: linear diameter of the carotid artery at the site of greatest narrowing.
- D: diameter of the normal artery distal to the carotid bulb, taken at the first point at which the arterial walls become parallel), whereas the ECST uses
- B: the estimated carotid bulb diameter. For example, using the NASCET definition, the degree of stenosis is shown in Equation.
- The relationship between the degree of narrowing based on the NASCET definition vs. that of the ECST has also been estimated by equation as shown in Equation.
- Angiography also affords the opportunity to perform endovascular intervention if indicated
Duplex Doppler ultrasound
- Velocity criteria (cm/s)
- Peak systolic velocity (PSV)
- End diastolic velocity (EDV)
- Doppler velocity ratios for ICA/CCA are 0.4 to 0.7 for normal vessels
Stenosis | PSV | EDV | IC/CC |
<50% | <125 | <40 | <2.0 |
50-69% | 125-230 | 40-100 | 2.0-4.0 |
≥70% | >230 | >100 | >4.0 |
- B-mode image evaluates the artery in cross-sectional plane, and spectrum analysis shows blood flow.
- Performs poorly with a “string sign.”
- Pros
- Low cost
- Non invasive
- Cons
- User dependent
- Limited anatomic information
- Cannot scan above the angle of the mandible.
- Lower frequencies give greater depth of penetration, but signal definition is sacrificed (used in transcranial Doppler).
- Sensitivity: 88%, specificity: 76%.
Magnetic resonance angiography (MRA)
- May obviate the need for angiography in some cases of carotid stenosis, specifically in symptomatic patients with a focal “gap” of signal intensity loss with distal reappearance of signal.
- Sometimes overestimates the degree of stenosis.
- Sensitivity: 91%, specificity: 88% for extracranial carotid disease.
- 2D TOF-MRA is adequate
- Contrast-MRA shows more, but is not necessary for surgical lesions.
- Pros
- Less operator dependent than Doppler
- Can be performed at the time as MRI with stroke protocol in TIA/stroke patients, and also detects thrombus or dissection.
- Cons
- More expensive
- Time-consuming
- Like Doppler, has difficulties distinguishing very severe stenosis from occlusion.
- MRA is more difficult to perform if the patient is critically ill, unable to lie supine, or has claustrophobia, a pacemaker or ferromagnetic implants.
- High-resolution MRI may also detect vulnerable plaques.
Computed tomography angiography (CTA)
- Pros
- CTA can be performed within a few seconds and yields high-resolution images of all vessels from the aortic arch through the intracranial/extracranial vessels as well as the surrounding soft tissues
- Ability to obtain CT-perfusion studies at the same time.
- Results are comparable to MRA and Doppler
- Cons
- Ionizing radiation (X-rays)
- IV iodinated contrast, limiting its use in patients with dye allergies and renal dysfunction.
- Sensitivity and specificity for detection of a 70% to 99% stenosis were 85% and 93%, respectively.
- CTA is still evolving and may help detect vulnerable plaques (p.1337).
Choice of imaging test/management decisions
- Doppler, CTA, or MRA are acceptable initial screening tests.
- If abnormal a second confirmatory noninvasive test to evaluate (doppler, CTA or MRA)
- If 2 noninvasive tests are discordant, catheter angiography should be considered before intervention
Treatment
Guidelines for the Primary Prevention of Stroke (A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association)
- Prescribed daily aspirin and statin
- Reasonable to consider CEA in asymptomatic patients with >70% stenosis if risk of perioperative stroke/MI/death is low (<3%), however, its effectiveness compared to BMT is not well established.
- Prophylactic CAS might be considered in highly selected patients, but its effectiveness compared to BMT is not well established.
- In patients at high risk of complication by either CEA/CAS, effectiveness of revascularization versus medical therapy alone is not well established.
Best medical management (BMT):
- General
- Unsure yet what is best medical management, always changing
- Some or all of the following are utilized:
- Anti-platelet therapy:
- Use one agent unless has had recent cardiac ischaemia or vascular stenting then use two agents
- Aspirin (ASA) (Main)
- Mech
- Irreversibly inhibits cyclooxygenase, preventing synthesis of
- Vascular prostacyclin (a vasodilator and platelet inhibitor) AND
- Platelet thromboxane A2 (a vasoconstrictor and platelet activator).
- Platelets, lacking cellular organelles, cannot resynthesize cyclooxygenase, whereas the vascular tissues do so rapidly --> end of day it is mainly a platelet inhibitor
- General:
- < 1000mg ASA per day probably does not help with high grade stenosis where there is perfusion failure or flow failure.
- Probably less effective in women
- No large study has shown that ASA prevents a second stroke in patients that have already had one
- Dose
- Cerebrovascular ischemia
- Optimal dose still debated.
- 325mg PO q d reduces risk of stroke following TIA by 25–30%.
- Post carotid endarectomy dose
- PO OD 81 or 325mg ASA has lower rate of stroke, MI, and death (6.2% vs. 8.4%) vs high doses
- Clopidogrel
- General:
- A thienopyridine.
- Side effects
- Incidence of severe neutropenia (0.04%) is close to that of ASA (≈ 0.02%).
- Mech
- Interferes with platelet membrane function by
- Inhibiting ADP-induced platelet fibrinogen binding
- Release of platelet granule contents
- Subsequent platelet-platelet interactions.
- Produces a time- and dose-dependent irreversible inhibition of platelet aggregation → prolongation of bleeding time.
- Indication
- Replace ASA if intolerance or resistance.
- Used in combination with ASA for some endovascular procedures and acute coronary syndromes, the MATCH results do not suggest a similar benefit for stroke and TIA.
- Combination therapy significantly increased risk of hemorrhage.
- Pharmacokinetics
- Dosed once daily.
- Requires several days to reach maximal effect
- ∴ a loading dose may be used, e.g. after an acute event such as an MI, or before stenting
- Takes ≈ 5 days off the drug for platelet inhibition to reverse.
- Dose
- 75mg PO qds
- Loading dose: 225mg (3 pills) the first day of therapy.
- Combination of extended release dipyridamole and ASA
- General
- More effective than ASA alone for prevention of TIA, stroke, and myocardial infarction
- No benefit from dipyridamole alone
- Combination was not superior to clopidogrel, with increased haemorrhage in the combination drug
- Dose
- 1 capsule PO BD
- 1 capsule: aspirin 25 mg + extended-release with dipyridamole 200mg
- Anti-hypertensive therapy
- Anti-diabetes therapy
- Anti-arrhythmic: asymptomatic A-fib should treatment with anticoagulation
- Cardiogenic brain embolism
- Antilipid therapy (statins)
- Anti smoking
Carotid endarterectomy
- Indication
- Based on degree of stenosis on angiography
- Yes for surgery
- >70% stenosis (not near occlusion), ARR of 16% (over 5 years), NNT = 6.3.
- Barnett et al 1998: 50 to 69% stenosis, ARR of 4.6% (over 5 years), NNT = 22.
- No for surgery
- 3-49% stenosis
- Harmful for < 30
- Timing of surgery
- Rothwell 2004
- Data combined from NASCET + MRC ECST
- The 5-year cumulative rate of ipsilateral ischemic stroke and any stroke or death within 30 days of CEA (vs. medical therapy) was reduced by
- >60% stenosis
Symptomatic (based on NASCET and MRC ECST) - set in stone
Timing to surgery | 5-year cumulative rate of ipsilateral ischemic stroke and any stroke or death within 30 days of CEA |
within 2 week | 18.5% |
2-4 weeks | 9.8% |
4-12 weeks | 5.5% |
12 weeks | 0.8% |
Asymptomatic
- High risk patients for CEA
- Prior head/neck surgery or irradiation
- Spinal immobility
- Restenosis post CEA
- Surgically inaccessible lesion
- Laryngeal palsy
- Laryngectomy
- Permanent contralateral cranial nerve injury
- Contralateral occlusion
- Severe tandem lesions
- Bilateral stenosis requiring treatment
- Age >75
- Congestive Heart Failure
- Left Ventricular Ejection Fraction <35%
- >2 diseased coronaries with >70% stenosis
- Unstable angina
- Myocardial infarction within 6 weeks
- Abnormal stress test
- Need for open heart surgery
- Need for major surgery (including vascular)
- Uncontrolled diabetes
- Severe pulmonary disease
Anatomical
Physiological
- Complication
- Postoperative stroke/death/MI
- AHA guidelines: 30 day stroke/death (<3% ASX; 6% SX)
- The overall rate of peri-operative stroke or death for all surgical patients within 30 days of trial surgery was 7.1%,
- Number needed to harm (NNH) of 14.
- Exploration for bleeding (1-4%);
- Wound infection (<1%)
- Cranial nerve injury (palsy vs permanent)
- Vagus, hypoglossal, facial nerves
- Significantly decreased from 8% to <2%
- Fewer than 1/7 are permanent
- Hyperperfusion syndrome (BP control)
- Recurrent stenosis (6% in 2 years)
- Outcome
- Restenosis risk after carotid endarterectomy
- 10% in first year
- 3% in second year
- 2% in third year
- 1% per year thereafter
Carotid angioplasty/stenting
- General
- 2007 Cochrane review concluded that available data on carotid angioplasty/stenting are difficult to interpret and does not support a change in clinical practice away from recommending CEA as the treatment of choice for suitable carotid artery stenosis
- SAPPHIRE study
- Comparing CEA with stenting (using a distal embolic protection device) for moderate to severe carotid stenosis with comorbidities that might increase the risk of CEA (high-risk patients),
- Finding
- Angioplasty/stenting was not inferior (risk within 3%, P= 0.004) to CEA (based on a composite primary end point of stroke, death, or MI within 30 days, or death from neurologic causes or ipsilateral stroke between 31 days and 1 year)
- SAPPHIRE's study method has been criticized
There are no well-designed studies that convincingly show superiority of angioplasty/stenting over CEA in average risk symptomatic patients, and the recommendation in these patients is to continue with the time-tested technique of CEA
Carotid angioplasty/stenting is as safe over the short term or as efficacious over the long term as CEA in average-risk symptomatic patients are lacking.
- Indications for angioplasty/stenting
- Severe vascular and cardiac comorbidities:
- Congestive heart failure (New York Heart Association class III/IV) and/or known severe left ventricular dysfunction
- Open heart surgery needed within 6 weeks
- Recent myocardial infarction (< 24 hours and > 4 weeks)
- Unstable angina (Canadian Cardiovascular Society class III/IV)
- Contralateral carotid occlusion
- Specific conditions:
- Contralateral laryngeal nerve palsy
- Radiation therapy to the neck
- Previous CEA with recurrent restenosis
- High cervical internal carotid/below the clavicle common carotid lesions
- Severe tandem lesions
- Age > 80 years
- Severe pulmonary disease
- Contralateral laryngeal nerve palsy,
- Previous radical neck dissection or cervical XRT,
- Prior CEA (re-stenosis),
- High bifurcation or intracranial extension of a carotid lesion,
- Provided that the peri-interventional stroke or death rate is not higher than that accepted for CEA (Class C recommendation).
- However, they stress that it remains uncertain whether this group of patients should have either procedure.
Carotid stenting performed with adequate procedural quality levels, should be considered instead of CEA in the presence of:
The 2009 European Society for Vascular Surgery (ESVS) Guidelines' indication
AHA Guidelines state that angioplasty/stenting might be a reasonable alternative to CEA in Asymptomatic high risk patients.
- Endovascular techniques: combined angioplasty and stenting (± distal embolus protection)
- Indicated
- High risk patient with asymptomatic carotid artery stenosis
- Catheterization
- Passage of aortic arch
- Catheterize target vessel
- Introduction of sheath
- “Unprotected” crossing of lesion
- Placement of embolic protection device (EPD)
- Intervention
- Balloon angioplasty
- Stent deployment
- Recovery of EPD
Causes of stroke during TF-CAS
Three Procedural Phases
- TransCarotid Artery Revascularization (TCAR)
- Newer Endovascular procedure
- Using blood flow reversal to reduce strokes
- ROADSTER trial
- N 208
- All high risk patients
- All-stroke rate in the group was 1.4% (This is for all patients with high surgical risk)
- Vs
- CREST CAS: 4.1% (standard surgical risk)
- CREST CEA: 2.3% (standard surgical risk
- ROADSTER 2 trial
- N 692
- All operators were TCAR Naïve operators
- All high risk patients
- 0.6% strokes
- 0.2% death
- 0.9% MI
Symptomatic
- General
- Benefit almost immediately from CEA due to their higher short-term stroke risk. However, even symptomatic patients with dense hemispheric neurological deficits, significant dementia, or severely limited functional status attributable to poor cardiac, renal, or pulmonary reserve are unlikely to benefit from any form of carotid revascularization.
- The degree of benefit individual symptomatic patients gained from carotid endarterectomy was directly proportional to the risk they faced without surgery
Symptomatic | Annual ipsilateral stroke rate | Any Mortality |
NASCENT | Surg 4.5% Med 13% | S 4.6% @ 2 yrs M 6.3% @ 2 yrs |
MRC ETC (>70% stenosis) | Surg 0.9% Med 5.6% | S 4.8% @ 3 yrs M 8.4% @ 3 yrs |
- CEA vs Best medical treatment
- N=659 (both males and females)
- Location
- US
- Canada
- Inclusion
- >70% stenosis on
- Symptomatic
- Hemispheric or retinal TIA
- Non disabling stroke
- Centres that did this operation well
- Less than 6% mortality or stroke, in more than >50 consecutive cases
- Surgical timing
- Exclusion
- >80 yrs
- Cant give consent
- Had organ failure
- Had cancer with < 5yrs of life left
- Had cerebral infarction that affected any function (disabling stroke)
- Non atherosclerotic disease (fibromuscular dyusplasia, aneurysm, tumour)
- Cardioembolic symptoms
- Previous ipsilateral carotid endarterectomy
- Randomisation
- Optimal medical care VS
- Antiplatelet therapy (1300mg aspirin per day)
- Surgical treatment
- Carotid endarterectomy
- Results
- Trial stopped early due to surgical benefits for severe stenosis
- Data here is for all grades of stenosis (show significant benefit from surgery in patients with ≥50% stenosis)
- Severe stenosis (70-99%)
- Medium-grade (moderate) stenosis (30-69%).
- Cumulative risk of any ipsilateral stroke at 2 yrs
- Surgical: 9%
- Medical: 26%
- Cumulative risk for fatal and major ipsilateral stroke at 2 yrs (6x)
- Surgical: 2.5%
- Medical: 13.1%
- Mortality
- Surgery: 4.6%
- Medical: 6.3%
- N=2200
- Mild stenosis (0-29%)
- 379 pt
- Very few had stroke in the absence of surgery
- 3 yr benefit of surgery is outweigh by risk --> no point doing surgery
- Moderate stenosis (30-69%)
- Uncertain benefit of surgery
- Severe stenosis (>70%)
- 778 pt
- Risk of surgery < benefit of surgery
- Risks of ipsilateral ischaemic stroke at 3 yrs were (8x)
- Surgical 2.8%
- Medical 16.8%
- Total risk of surgical death, surgical stroke, ipsilateral ischaemic stroke, or any other stroke at 3 yrs
- Surgical 12.3%
- Medical 21.9%
- Risk of disabling or fatal events at 3 yrs
- Surgical 4.8%
- Medical 8.4%
- Total 3-year risk of any disabling or fatal stroke (or surgical death)
- Surgical 6.0%
- Medical 11.0%
- 3 yrs follow up
- N=189
- Men only
- Results
- 1 yr risk of stroke and TIA
- Surgical: 7.7%
- Medical: 19.4%
- Benefit greatest when stenosis is > 70% u/s duplex
North American Symptomatic Carotid Endarterectomy Trial (NASCET): Barnett 1991 Mendeley
MRC European Carotid Surgery Trial 1991:
Carotid Endarterectomy and Prevention of Cerebral Ischemia in Symptomatic Carotid Stenosis: Mayberg 1991 Mendeley
Asymptomatic
- General
- Best medical therapy alone may be preferred for asymptomatic carotid occlusion if
- Patient life expectancy is less than the time to achieve stroke reduction benefit from revascularization (i.e. 2-3 years for CEA, and 5 years for CAS),
- Established periprocedure risk of death/stroke is small enough (< 3%) and/or high future stroke risk factors (e.g. plaque ulceration, contralateral ICA occlusion, male, intraluminal thrombus, young age) to ensure benefit despite small absolute risk reduction seen in studies (6% at 5 years in ACAS).
- CEA vs Best medical treatment
- 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. However, the absolute risk reduction is small (approximately 1% per annum 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
- The largest multicenter randomized trial to date
- Moderate benefit for immediate CEA vs. medical management in patients age < 75 with asymptomatic stenosis ≥ 60%.
- N=3,120 patients
- Inclusion criteria
- ≥60% stenosis on duplex ultrasound
- Surgeons were required to have a perioperative morbidity and mortality rate of< 6%.
- Exclusion criteria:
- Poor surgical risk
- Prior ipsilateral CEA
- Probable cardiac emboli
- Randomized: at the discretion of the treating physician
- Immediate CEA (50% had CEA within 1 month, 88% within 1 year) or
- Medical therapy
- Using USS to determind stenosis
- Follow-up: 3.4 years.
- Results
- Net 5-year risk for all stroke or perioperative stroke or death: (p < 0.0001)
- CEA group: 6.4% vs.
- Medical group: 11.8%
- Fatal or disabling (mRS>2) stroke:
- CEA group: 3.5 % vs.
- Medical group 6.1%.
- Fatal stroke alone:
- CEA group: 2.1 % vs.
- Medical group 4.2 %.
- Although men and women benefited, men benefited more.
- CEA did not demonstrate a statistically significant benefit for patients over the age of 75.
- Statistical benefit was not seen in the immediate CEA group until nearly two years after surgery despite a relatively low perioperative morbidity and mortality rate of 3.1%
- (In contrast to patients with symptomatic stenosis (NASCET) where benefit was seen much earlier).
- Large trial that randomized patients in good health with asymptomatic stenosis (calculated in the same manner as the NASCET study)
- N=1659
- Randomisation
- CEA plus aspirin (325mg)
- Within 2 wks of randomisation
- Aspirin
- Using USS (medical) and angiography (surgical) to determined stenosis
- Inclusion
- 60% stenosis on arteriogram
- 40-79 yrs
- Exclusion
- Age > 79 yrs
- Unstable CAD
- Uncontrolled HTN
- Cerebrovascular events in the distribution of the study carotid artery or in the vertebrobasilar arterial system
- Results
- The study group was 95% Caucasian, and 66% were male.
- NNT 17
- 5 year risk of ipsilateral stroke
- Medical: 11%
- Surgical: 5.1%
- 5 year major ipsilateral stroke
- Medical 6%
- Surgical 3.4%
- Surgery
- Perioperative stroke rate 2.3% (NNH: 43)
- Did not significantly protect against major stroke or death (P = 0.16) (half of the strokes were not disabling),
- Was somewhat protective against any stroke or death (P = 0.08).
- Total mortality risk in 5 yrs
- Surgical
- 3.5%
- Medical
- 3.8%
- Combined stroke and death rates in community hospitals, while improved over the last 20 yrs, remains higher at ≈ 6.3% than at centers used in this study.
- Note
- Surgeons were carefully selected
- Surgical morbidity (1.5%) and mortality (0.1%) was very low.
- Half of the total morbidity (1.2%) was related to angiography.
- Conclusion
- For a generally healthy white male with ACAS > 60%, management with CEA (when performed by a surgeon with a low complication rate, as described) reduces his annual risk of all strokes from 0.5% to 0.17% (the reduction of risk for severe stroke is less).
- The benefit from CEA is realized within less than one year after the CEA.
- This is in contrast to the ACST trial (see above) and is most likely due to the lower perioperative event rate.
- N=444
- Only Men no women included
- >50% stenosis
- Randomisation
- Optimal medical tx (antiplatelet)
- Surgery
- Optimal medical tx (antiplatelet)
- Carotid endarterectomy
- Results
- Incidence of ipsilateral neurologiucal events
- Surgical
- 8.0%
- Medical
- 20.6%
- Incidence of ipsilateral stroke
- Surgical 4.7%
- Medical 9.4%
- All strokes and deaths: similar between two
- Surgical 41.2%
- Medical: 44.2%
- N=410
- Inclusion
- Stenosis: 50-90% angiography/doppler
- Exclusion
- >90% stenosis
- <50% stenosis
- Previous carotid surgery
- 3 yrs follow up
- Randomisation into two groups
- A
- Were operated on unilaterally if they had a unilateral stenosis or bilaterally if they had bilateral stenosis of the ICA.
- B
- Patients in group B were not operated on in case of unilateral stenosis
- Treatment: odd protocol
- Surgical
- Medical +
- Carotid enterectomy
- Medical
- 330 mg acetylsalicylic acid and 75 mg dipyridamole three times daily
- No difference in outcome between CEA vs. aspirin (new stroke or death), but an unusual protocol lessened its statistical validity
- Surgically treated patients were not given aspirin
- Trial was terminated early because of a significantly higher number of myocardial infarctions and transient cerebral ischemic events in the surgical group than in the medical group
- Results
- No major strokes or deaths in either the medical or the endarterectomy group.
- Risk of MI
- Surgical: 26%
- Medical: 9%
- This study shows you need to give aspirin regardless of treatment arm
Asymptomatic carotid endarterectomy
Studies
Asymptomatic Carotid Surgery Trial (ACST) 2004:
Asymptomatic Carotid Atherosclerosis Study (ACAS) 1995:
Efficacy of carotid endarterectomy for asymptomatic carotid stenosis 1993: Hobson mendeley
Carotid Artery Stenosis with Asymptomatic Narrowing: Operation Versus Aspirin (CASANOVA)
Mayo Clinic Asymptomatic Carotid Endarterectomy (MACE) Study
CEA vs CAS
Symptomatic
- International Carotid Stenting Study (ICSS) randomised trial
- No difference in CEA or CAS in terms of functional outcome and debilitating stroke.
- Any stroke was higher with CAStent
Asymptomatic
- Kakkos et al 2017 meta analysis
- For asymptomatic stenosis undergoing carotid intervention, CEA had significantly lower 30-day stroke and also stroke or death rates compared with CAS at the cost of higher CNI and non-significantly higher MI rates.
- Stroke or death rate at 30 days: CAS (2.94%) vs CEA (1.89%) OR, 1.57
- Reasons why carotid stenting might result in a lower rate of MI:
- Less Invasive: reduces the overall stress the heart.
- Shorter Recovery Time
- Wang et al 2022 Meta analysis
- Forest plots of long time outcomes of composite outcome among any perioperative stroke, death, or myocardial infarction (MI) and long-term stroke, death, or MI in randomized controlled trials comparing carotid artery stenting (CAS) vs carotid artery endarterectomy (CEA) in patients with asymptomatic carotid stenosis.
Stenting and Angioplasty with Protection in Patients at High Risk
- Major Eligibility Criteria
- General criteria
- Age ≥18 yr
- Unilateral or bilateral atherosclerotic or restenotic lesions in native carotid arteries
- Symptoms plus stenosis of more than 50 percent of the luminal diameter
- No symptoms plus stenosis of more than 80 percent of the luminal diameter
- Criteria for high risk (at least one factor required)
- Clinically significant cardiac disease (congestive heart failure, abnormal stress test, or need for open-heart surgery)
- Severe pulmonary disease
- Contralateral carotid occlusion
- Contralateral laryngeal-nerve palsy
- Previous radical neck surgery or radiation therapy to the neck
- Recurrent stenosis after endarterectomy
- Age >80 yr
- Ischemic stroke within previous 48 hr
- Presence of intraluminal thrombus
- Total occlusion of target vessel
- Vascular disease precluding use of catheter-based techniques
- Intracranial aneurysm >9 mm in diameter
- Need for more than two stents
- History of bleeding disorder
- Percutaneous or surgical intervention planned within next 30 days
- Life expectancy <1 yr
- Ostial lesion of common carotid artery or brachiocephalic artery
Inclusion criteria
Exclusion criteria
- Among patients with severe carotid-artery stenosis and coexisting conditions, carotid stenting with the use of an emboli-protection device is not inferior to carotid endarterectomy
- But not well powered to say CAS is better than CES
The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)
- CAS and CEA had similar short- and longer-term outcomes. During the periprocedural period, there was higher risk of stroke with CAS and higher risk of myocardial infarction with CEA.
Second asymptomatic carotid surgery trial (ACST-2) Halliday 2021 Mendeley
- International multicentre randomised trial
- Procedural stroke: stroke with 30 days of procedure
- 130 centres
- Vascular surgeon, an interventionalist (perhaps the same person), and a neurologist (or stroke doctor).
- The risks of any stroke or death had to be 6% or lower for symptomatic patients and 3% or lower for asymptomatic patients.
- 5 yrs follow up
- Inclusion
- If they had severe unilateral or bilateral carotid artery stenosis (generally 60% or higher on ultrasound);
- Carotid artery stenosis assessed duplex Doppler
- This had not caused any relevant neurological symptoms in the preceding 6 months;
- There was CT or MRI confirmation of suitability for CAS and for CEA (which would also have been used to exclude from trial entry any patient without sufficient stenosis to justify intervention);
- The doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain whether this should be CAS or CEA;
- The patient had no known circumstance or condition likely to preclude long-term follow-up
- Exclusion
- Previous ipsilateral intervention,
- Unsuitability for CAS (eg, due to calcification or tortuosity) or CEA,
- High procedural risk (eg, because of recent acute myocardial infarction),
- High risk of cardiac emboli, or any major life-threatening condition.
- Patients likely to require other surgery could not enter the trial until at least 1 month after it
- Crossover
- CAS --> CEA
- Stenosis was highly calcified
- Carotid artery was more tortuous than anticipated.
- CEA --> CAS (3%)
- Patient’s or doctor’s preference, or reluctance to undergo general anaesthesia.
- Only about half the CAS procedures were done by a radiologist; most of the others were done by vascular surgeons.
Features | Carotid Artery Stenting (CAS) | Carotid Endarterectomy (CEA) | Overall |
N | 1811 | 1814 | 3625 |
Disabling stroke or death procedurally (<30 days) | 1% | 0.9% | 0.7% |
Non-disabling procedural stroke (<30 days) | 2.7% | 1.8% | 2.2% |
5-year non-procedural fatal or disabling stroke, | 2·5% | 2·5% | 2.5% |
5-year non-procedural any stroke | 5.2% | 4.5% | 4.8% |
- Outcome:
- Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable.
- THERE IS NO DIFFERENCE BETWEEN CAS vs CES
Patient Selection in Carotid Endarterectomy vs Stenting
Factors | Carotid Endarterectomy (CEA) plus BMT | Carotid Artery Stent (CAS) plus BMT |
Age | Safer than CAS in patients ≥70 years of age. | Significantly increased risk of periprocedural stroke or death in CAS-treated patients ≥70 years of age. |
Life expectancy to see stroke reduction relative to BMT alone | At least 3 years | At least 5 years |
Stroke risk factors present | Ipsilateral neurology in last 6 months High grade (70-99%) stenosis High risk plaque (ulcer, hemorrhage etc.) Contralateral carotid occlusion increases risk of CEA (inadequate collateral circulation) | Not suitable for lesions at high risk of periprocedural embolization (e.g. intraluminal thrombus) |
Neck anatomy | Challenging if hostile neck anatomy Unclear if preferable to CAS for recurrent carotid artery stenosis | Preferred for patients with hostile neck (previous neck surgery/radiotherapy, contralateral laryngeal nerve palsy, tracheostomy) |
Carotid/aortic arch anatomy | Better outcomes than CAS if: ICA-CCA angulation >60 deg., ICA lesion >10-15 mm long, ostial involvement of lesion, excessive calcification | Preferred if hostile carotid: lesion distal to C2 vertebral body or proximal to clavicle Increased risk of periprocedural stroke if aortic arch challenging configuration, tortuous, calcified. |
Stroke risk reduction and outcome | 16% absolute risk reduction at 2 years compared to BMT alone in symptomatic patients in NASCET (overall 10% risk reduction once 6% perioperative risk considered) | Conflicting evidence as to whether non-inferior to CEA. Worse outcomes in symptomatic patient and >70. Non-inferior to CEA in high risk patients |
Complications | Greater risk of MI and cranial nerve injury compared to CAS Lower risk of periprocedural stroke risk than CAS | Higher stroke risk and death Lower risk of MI |
CEA
Randomized trials of CEA vs Medical Therapy for Carotid Artery Stenosis:
- Carotid endarectctomy better than best medical treatment for both symptomatic and asymptomatic disease
- Pooled analysis of 6,092 symptomatic patients with 35,000 patient-years of follow-up (NASCET, ECST, VA 309) revealed a 1.1% mortality and a 7.1% incidence of stroke or death at 30 days after CEA. After 5 years, CEA was associated with:
- 48% relative risk reduction in ipsilateral stroke in patients with stenosis 70% to 99%,
- 28% relative risk reduction in ipsilateral stroke in patients with stenosis 50% to 69%,
- And no benefit in patients with stenosis less than 50%
- If patients survive for more than 2 yrs is beneficial to have CEA.
- Pooled analysis of 5,223 asymptomatic patients with 17,037 patient years follow-up (Veterans Affairs Cooperative Study, ACAS, and ACST), revealed at 30 days, the risk of stroke or death after CEA was 2.9%.
- In comparison with aspirin alone, CEA was associated with a 31% relative risk reduction in stroke or perioperative death during the study period, but the absolute risk reduction was only 1% per year.
- Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) is a randomized, controlled trial with blinded end-point adjudication.
- The primary aim was to compare the outcomes of carotid-artery stenting with those of carotid endarterectomy among patients with symptomatic or asymptomatic extracranial carotid stenosis.
- Secondary aims included estimating the modification of the treatment effect by symptomatic status, sex, and age, which were assessed through inclusion of the interaction terms in the proportional-hazards models.
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