WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTIS STENOSIS

1. WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTIS STENOSIS ROBERTO GATTUSO Chair of Vascular Surgery – Sapienza University - Rome

2. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? Ischaemic stroke rapresents today a main problem in public health and is a major cause of long-term disabling in the general population ranging from sixty to ninety years. Mortality for stroke ranges from 10% to 30% and patients who survive remain at high annual risk for recurrent ischaemic stroke and mortality for myocardial infarction and fatal repeated stroke. The common caroitid bifurcation is a major condiotion that can cause a recurrent ischaemic stroke accounting for about 20% of all strokes. But in the remaining 80% this relationship is not clear so that a careful patients follow-up is mandatory.

3. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? The efficacy of carotid endarterectomy (CEA) in preventing stroke in patients with lesions of the internal carotid artery is well estabilished and up to date is the gold standard therapy. This approach needs to be compared and validated with the new emergent endovascular techniques . The routine use of new drugs like antiplatelets, that are able to reduce stroke incidence, and statins, that have shown to have a stabilising effect on atheromatous plaque, need a better complete evaluation in determining their role.

4. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? CEA CAS BEST MEDICAL TREATMENT

5. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? INDICATIONS FOR TREATMENT # NEUROLOGICAL SYMPTOMS # DEGREE OF CAROTID STENOSIS # MEDICAL COMORBIDITIES # VASCULAR AND LOCAL ANATOMY # CAROTID PLAQUE MORPHOLOGY - SYMPTOMATIC PATIENTS - ASYMPTOMATIC PATIENTS

6. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? European Carotid Surgery Trial (ECST) and North American Symptomatic Carotid Endarterectomy Trial (NASCET) HAVE CLEARLY SHOWED THAT: # CEA has increased the 5 yrs risk of ipsilateral ischaemic stroke in pts with less than 30% stenosis (p=0.05) # CEA has no effect in pts with 30-49% stenosis (p=0.6) # CEA has low benefit in pts with 50% to 69% stenosis (p=0.04) # CEA was highly beneficial in those with 70% or greater without preocclusive lesions (p=0.001) # the randomization within 2 weeks after the last ischaemic event increased the effectiveness of surgery (p= 0.009) # the associated incidence of death/stroke for CEA is </=1.9%

7. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? Asymptomatic Carotid Atherosclerosis Trial (ACAS) Have estimated that the cumulative 5 year risk of ipsilateral stroke and any perioperative stroke or death was 5.1% for the surgical group and 11.0% for patients treated medically (aggregate risk reduction of 53%). Asymptomatic Carotid Surgery Trial (ACST) In asymptomatic patients (age <75 yrs and 70% carotid stenosis),immediate CEA halved the net 5-years stroke risk from 12% to 6%. This benefit was demonstrated for fatal, disabling and non-disabling strokes. These data were not confirmed for women

8. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? European Society for Vascular Surgery GUIDELINES INVASIVE TREATMENT FOR CAROTID STENOSIS: INDICATIONS AND TECNIQUES # “CEA is absolutely indicated in symptomatic patients with 70% (NASCET) stenosis and probably with 50% to 70% (NASCET) stenosis (A). The perioperative stroke/death incidence should be<6% (A). CEA is controindicated for symptomatic patients with less tha 50% stenosis (A)” # “CEA should be performed within two weeks of the patient’s last symptoms (A)”

9. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? European Society for Vascular Surgery GUIDELINES INVASIVE TREATMENT FOR CAROTID STENOSIS: INDICATIONS AND TECNIQUES # “CEA can be recommended for asymptomatic men below 75 years with 70% to 99% stenosis if the risk associated with surgery is less than 3% (A)” # “The benefit from CEA in asymptomatic women with carotid stenosis is significantly less than in men (A). CEA should be therefore considered only in younger, fit women (A)”

10. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? NEURO-PROTECTION DEVICE EXPANDIBLE BALLOON STENT GUIDING CATHETER

11. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? Safety of endovascular treatment of carotid artery Stenosis compared with surgical treatment: a meta-analysis. JVS 2008; 47:350 Meta-analysis by Cochrane Collaboration on 2985 pts of 8 trials (CAVATAS, Kentucky, Leicester, Wallstent, SAPPHIRE, EVA-3S, SPACE and BACASS) in wich 89% were symptomatic six months before enrollement. “In contrast to previous analyses, this meta- analysis found a significant difference between the odds ratios of any stroke or death within 30 days after treatment with a disadvantage of endovascular treatment when analysing all trials: odds ratio 1.38”

12. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? Safety of endovascular treatment of carotid artery Stenosis compared with surgical treatment: a meta-analysis. JVS 2008; 47:350 Meta-analysis by Cochrane Collaboration on 2985 pts of 8 trials (CAVATAS, Kentucky, Leicester, Wallstent, SAPPHIRE, EVA-3S, SPACE and BACASS) in wich 89% were symptomatic six months before enrollement. “In contrast, in the same meta-analysis, no statistically significant differences were found or MI, or death and stroke during long term follow-up” .

13. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? EVA – 3S PERI-PROCEDURAL STROKE/DEATH INCIDENCE: CAS: 9.6%CEA: 3.9% STROKE/DEATH INCIDENCE AT 4 YEARS: CAS: 4.94%CEA: 4.49% SPACE PERI-PROCEDURAL STROKE/DEATH INCIDENCE + IPSILATERAL ISCHAEMIC STROKE AT 2 YRS: CAS: 9.5%CEA: 8.8%

14. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? EVA 3S SPACE RSTENOSIS INCIDENCE: 10.7% in CAS and 4.6% in CEA (in the intention to treat group) 11.1% in CAS and 4.6% in CEA (in the per-protocol population)

15. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? European Society for Vascular Surgery GUIDELINES INVASIVE TREATMENT FOR CAROTID STENOSIS: INDICATIONS AND TECNIQUES # The available level I evidence suggets that for symptomatic patients, surgery is currently the best option (A) # Mid-term stroke prevention after successful CAS is similar to CEA (A) # CAS should be offered to symptomatic, if they are at high risk for CEA, in high volume centres with documented low peri-procedural stroke and deaths rate or inside a RCT (C)

16. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? ASYMPTOMATIC PTS AND CAS In several centres if a patient is fit for surgery he could be also a candidate for CAS. SAPPHIRE Trial Study RCT in high risk patients - 2004 334 pts ( 167 CEA – 167 CAS ) 70.1% were asymptomatic Death/stroke/MI at 30 days 9.9% CEA versus 4.4% CAS – p=0.08 Death/stroke/MI at1 year 3.5% CEA versus 0% CAS – p=0.02

17. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? ASYMPTOMATIC PTS AND CAS In several centres if a patient is fit for surgery he could be also a candidate for CAS. # There is no available RCT data that prove the effectiveness of CAS over a specific cut-off point of the degree of carotid stenosis. # There is no available RCT data that compare the best medical treatement to CAS in symtomatic and asymptomatic patients

18. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? Asymptomatic Carotid Surgery Trial (ACST-2) Is a new randomized trial that compares CAS and CEA in asymtomatic patients BREAKING NEWS Transatlantic Asymptomatic Carotid Intervention Trial (TACIT) Is a multinational randomized trial that compare BMT to CAS and BMT to CEA in asymptomatic patients

19. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? European Society for Vascular Surgery GUIDELINES INVASIVE TREATMENT FOR CAROTID STENOSIS: INDICATIONS AND TECNIQUES Meanwhile, it is advisable to offer CAS in asymptomatic patients only in high-volume centres with documented low peri-procedural stroke and death rates or within well-conducted clinica trials. The assumption that a patient can be treated with CAS when he has an indication to CEA, has not yet been validated There is no randomized evidence on the specific threshold in the degree of stenosis over which there is an indication to CAS, neither in symptomatic nor asymptomatic patients.

20. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? HIGH RISK PATIENTS ? European Society for Vascular Surgery GUIDELINES INVASIVE TREATMENT FOR CAROTID STENOSIS: INDICATIONS AND TECNIQUES CEA can be performed in high risk patients with cardiac, stroke and death rate well within accepted standards (B) CAS is associated to higher embolization risk in octagenarians if compared to CEA (B) CAS shoulb be offered to asymptomatic high risk patients if the peri-procedural complication is < 3% (C) CAS is indicated in case of controlateral nerve palsy, previous radical neck dissection, cervical irradiation, restenosis, high bifurcation and extension of the plaque towards the skull base (C)

21. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? ONGOING QUESTIONS NEW TECHNOLOGY CERVICAL APPROACH PLAQUES MORPHOLOGY CEREBRAL EMBOLIZATION COGNITIVE TESTS ARCH AND CAROTID ANATOMY

22. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? 92 YEARS OLD SYMPTOMATIC WOMAN

23. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? CAROTID PLAQUE AFTER CEA

24. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ? CAS >< CEA WHAT’S THE BEST TREATEMENT….. FOR THE BRAIN ?

25. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ?

26. Chair of Vascular Surgery “Sapienza University” - Rome WHAT’S THE BEST TREATMENT FOR INTERNAL CAROTID STENOSIS ?