Is Carotid Stenting an Option for Treatment of Carotid Stenosis?

Joint Hospital Surgical Grand Round

WH WONG Queen Mary Hospital

Carotid stenosis- pathophysiology

Early degenerative plaque formation(cholesterol/ lipids/ inflammatory cells)

⇓ ulceration/ haemorrhage

Flow limiting stenosis

⇙ ⇘

Thrombosis Embolism

Spagnoli LG et al., JAMA 2004

Investigation modalities

Carotid duplex ultrasonography

diagnostic study of choice for screening

very accurate predictability for high grade lesion (70% stenosis)

CT/ MRI angiography

useful in collaboration with USG for further characterization of lesion producing >50% stenosis

Cerebral angiography

gold standard for accurate characterization of plaque and collateral circulation

Treatment modalities

Risk factors modification

Best medical therapy

Surgical treatment

Risk factors modification

Hypertension

OR of 2.11 for every 20mmHg increase in systolic pressure

Dyslipidaemia

OR of 1.1 for every 10mg/dL in cholesterol

Diabetes

Smoking

OR of 1.08 for every 5 pack-years of smoking

Stroke 1990N Engl J Med 1997

Circulation 2004

Best medical therapy: Antiplatelets

Antithrombotic Trialists’ collaboration (BMJ 2002)

Aspirin reduces the risk of TIA/ stroke/ death as monotherapy in high-risk patients

Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) (Circulation 2005)

Combination therapy reduces the incidence of asymptomatic embolization

Surgical treatment

Carotid endarterectomy (CEA)

?? Carotid angioplasty and stenting (CAS)

Superiority of CEA: Asymptomatic stenosis

Veterans Affairs Cooperative Trial (N Engl J Med 1993)

444 patients, asymptomatic stenosis >50%, Aspirin + CEA vs Aspirin

Lower incidence of ipsilateral stroke/ TIA (8.0% vs 20.6%, P< 0.001)

No difference in mortality in 30 days and 4 years

Asymptomatic Carotid Atherosclerosis Study (ACAS) (JAMA 1995)

1662 patients, asymptomatic stenosis > 60%, Aspirin +CEA vs Aspirin

Cerebral infarction decreased in surgery group (5.1% vs 11%)

Asymptomatic Carotid Surgery Trial (ACST) (Lancet 2004)

3120 patients, asymptomatic stenosis >60%

5 years risk reduction in stroke/ death in CEA group (6.4% vs 11%)

Superiority of CEA: Symptomatic stenosis

North American Symptomatic Carotid Endarterectomy Trial (NASCET) (N Engl J Med 1998)

randomised, prospective multicentre trial of 659 patients with symptomatic stenosis >70%

lower cumulative risk of any ipsilateral stroke at 2 years (9% vs 26%, P< 0.001)

reduction in rate of major/ fatal stroke in 2 years (2.5% vs 13.1%, P< 0.001)

European Carotid Surgery Trial (ECST) (Lancet 1998)

2518 patients

surgery benefits most to patients with severe stenosis >70%

Superiority of CEA

American Heart Association

American Stroke Association

Grade IA indication for CEA in carotid stenosis >70% regardless of symptom status

Grade IIA recommendation for CEA in asymptomatic men aged of 40-75 years with >60% stenosis

Surgery in only symptomatic women

Circulation, 2006

Any place for CAS?

Background of CAS

First successful carotid angioplasty by Klaus Mathias in 1980

Angioplasty without stent placement: poor results and complications

Primary adverse event in carotid atherosclerosis is embolization of plaque material

Stenting provides effective means of mechanical “plaque stabilization”

Carotid angioplasty with stenting readily replaces lone balloon angioplasty

CAS in symptomatic carotid stenosis

Stent-Protected Angioplasty vs Carotid Endarterectomy (SPACE) Trial

randomized multi-centre non-inferiority trial

1183 patients with severe symptomatic stenosis (>70%)

no significant difference between CAS and CEA in

30-day rate of stroke (6.84% vs 6.34%)

30-day rate of any stroke or death (7.7% vs 6.5%)

1 year rate of any stroke or death (9.6% vs 8.7%)

Failed to show non-inferiority of CAS in treatment of severe carotid stenosis

SPACE Collaborative Group, Lancet 2006

CAS in symptomatic carotid stenosis

Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) Trial

randomized multi-centre non-inferiority trial

527 symptomatic patients with severe stenosis (60-90%)

30-day rate of any stroke or death in CAS and CEA: 9.6% vs 3.9%

Failed to establish non-inferiority of CAS vs CEA

N Engl J Med 2006

CAS in symptomatic carotid stenosis

International Carotid Stenting Study (ICSS)

randomized controlled trial of 1713 patients

recently symptomatic carotid stenosis >50%

determine long-term survival free of disabling stroke

sufficient follow-up to be complete in 2011

30-day rate of stroke/ MI/ death of CEA and CAS: (5.1% vs 8.5%, hazard ratio 1.73, P=0.004)

Clear superiority of CEA over CAS

Cerebrovasc Dis 2009

CAS in asymptomatic carotid stenosis

Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) Trial

randomized multi-centre trial of 334 patients

68% patients asymptomatic with stenosis >80%

32% patients symptomatic with stenosis >50%

high risks: > 80 years/ significant heart or pulmonary disease/ contralateral carotid occlusion/ laryngeal nerve palsy/ prior radical neck surgery/ radiotherapy/ post-CEA restenosis

30-day MI/ stroke/ death rate for CAS/ CEA: 4.8% vs 9.8%, P= 0.09

1-year MI/ stroke/ death rate for CAS/ CEA: 12.2% vs 20.1%, P=0.048

CAS not inferior to CEA in treatment of high risk groupSAPPHIRE Investigators, N Engl J Med 2004

CAS in both asymptomatic and symptomatic carotid stenosis

Carotid Revascularization Endarterectomy vs Stent Trial (CREST)

prospective randomized multicentre trial of 2502 patients

108 centres in the USA

9 centres in Canada

both symptomatic (>50%) and asymptomatic (70%) carotid stenosis

exclusion criteria:

previous stroke severe enough to confound assessment of end-points

atrial fibrillation within 6 months/ necessitates anticoagulation

myocardial infarction within 30 days/ unstable angina

CREST Investigators, N Engl J Med 2010

During the periprocedure period, the incidence of the primary end-point was similar (5.2% vs 4.5%, hazard ratio for CAS, 1.18; P=0.01)

myocardial infarction more in CEA group (1.1% vs 2.3%, P=0.03)

stroke more in CAS group (4.1% vs 2.3%, P=0.01)

No significant difference from estimated 4-year rates of the primary end-point (7.2% vs 6.8%, hazard ratio for CAS, 1.11; P=0.51)

stroke rate in CAS still higher (6.4% vs 4.7%, P=0.03)

Findings from CREST

No modification of treatment effect by

symptomatic status (P=0.84)

gender (P=0.34)

Findings from CREST

Findings from CREST

Interaction between age and treatment effect (P=0.02)

vascular tortuosity

severe vascular calcification

Findings from CREST

CAS is associated with higher periprocedural risk of stroke, still significantly evident at 4 years

CEA is associated with higher periprocedural myocardial infarction and cranial palsies

Incidence of primary outcomes in both CAS and CEA is impressively low

• importance of training, credentialing & auditing of proceduralists

Selection for treatment requires attention to age

younger patients have better outcomes with CAS

older patients have better outcomes with CEA

Conclusion from CREST

Take home message

Strength of recommendationGrade 1: strong

Grade 2: weak

Quality of evidence

High: well conducted, large consistent RCTs

Moderate: inconsistent RCTs, observational studies

Low: observational studies, case series

Clinical guideline

Low grade stenosis (symptomatic <50%/ asymptomatic <60%)

optimal medical treatment (grade 1 recommendation; high quality evidence)

Symptomatic moderate to severe stenosis (>50%)

CEA + optimal medical treatment (grade 1 recommendation; high quality evidence)

Symptomatic moderate to severe stenosis (>50%) & high risk

CAS as an potential alternative to CEA (grade 2 recommendation; low quality evidence)

Asymptomatic moderate to severe stenosis (>60%)

CEA + optimal medical treatment (grade 1 recommendation; high quality evidence)

Against CAS except stenosis >80% or high anatomical risk for CEA (grade 1 recommendation; low quality evidence)

J Vasc Surg 2008

Thank you