WH WONG Queen Mary Hospital

1. Is Carotid Stenting an Option for Treatment of Carotid Stenosis?Joint Hospital Surgical Grand Round • WH WONG • Queen Mary Hospital

2. Carotid stenosis- pathophysiology Spagnoli LG et al., JAMA 2004

3. 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

4. Treatment modalities • Risk factors modification • Best medical therapy • Surgical treatment

5. 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 1990 N Engl J Med 1997 Circulation 2004

6. 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

7. Surgical treatment • Carotid endarterectomy (CEA) • ?? Carotid angioplasty and stenting (CAS)

8. Superiority of CEA: Asymptomatic stenosis • Veterans Affairs Cooperative Trial (N Engl J Med1993) • 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%)

9. Superiority of CEA: Symptomatic stenosis • North American Symptomatic Carotid Endarterectomy Trial (NASCET) (N Engl J Med1998) • 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%

10. 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

11. Any place for CAS?

12. 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

13. 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

14. 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

15. 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

16. 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 group SAPPHIRE Investigators, N Engl J Med 2004

17. 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

22. Findings from CREST • 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)

23. Findings from CREST • No modification of treatment effect by • symptomatic status (P=0.84) • gender (P=0.34)

24. Findings from CREST • Interaction between age and treatment effect (P=0.02) • vascular tortuosity • severe vascular calcification

25. Findings from CREST

26. Conclusion 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

27. Take home message

28. 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

29. Thank you