International Carotid Stenting Study (ICSS) Dr. Rahi Kiran Senior Resident Department of Neurology GMC, Kota.

1. Dr. Rahi Kiran
Senior Resident
Department of Neurology
GMC, Kota.

2. This article was published in
Lancet Neurol. May 31, 2018

3. Introduction
 symptomatic carotid stenosis - with stroke or TIA in
the preceding 6 months
 For non vascular surgeries <0.5%

4. 2018 ESVS recommendations
symptomatic carotid artery disease –
 CEA recommended rather than CAS-
 symptoms <6 months,70%–99% carotid stenosis-I, A
 symptoms <6 months, 50%–69% carotid stenosis-IIa, A
 symptoms <6 months,age >70yrs, 50%–99% carotid
stenosis-I, A
 CAS may be considered an alternative to CEA,
symptoms <6 months, age <70yrs-IIb, A
 performed as soon as possible, preferably within 14 days
of symptom onset. Perform CEA, rather than CAS- I, A

5. 2018 ESVS (European Society for Vascular Surgery)
Guidelines
 clinical/Imaging features associated with an increased
risk of stroke in patients with asymptomatic carotid
stenosis treated medically
 Clinical History of contralateral TIA or stroke
 CT/MRI ipsilateral ‘silent’ infarction
 Ultrasound Stenosis progression>20%; large volume
plaques (>80 mm2)
 MRI Intraplaque haemorrhage

6.  In ‘average surgical risk’ patients with an
asymptomatic 60%–99% stenosis, CEA should be
considered in the presence of 1+ imaging
characteristics that may be associated with an
increased risk of late ipsilateral stroke, provided the
patient’s life expectancy exceeds 5 years and CAS may
be an alternative to CEA or if CEA is contraindicated
Class IIb Level B
2018 ESVS recommendations
asymptomatic carotid artery disease –

7. International Carotid Stenting Study (ICSS)
 Largest randomised trial reporting long-term
restenosis of various severity and subsequent risks of
stroke after stenting versus endarterectomy for
treatment of symptomatic carotid stenosis.

8. AIMS
 to quantify the long-term risk of at least moderate
(≥50%) restenosis up to 10 years after randomisation,
 to ascertain whether restenosis predisposed to a higher
risk of subsequent stroke after either procedure,
 To investigate the risk factors predisposing to
restenosis.

9. Inclusion criteria
 Symptomatic atheromatous carotid stenosis > 50% by
NASCET criteria, suitable for stenting and surgical
endarterectomy
 carotid stenosis associated with ipsilateral transient ischemic
attack or stroke symptoms within the 12 months before
inclusion.
 age greater than 40
 clinically stable
 Willing

10. Inclusion criteria – secondary analysis
 randomly allocated treatment was initiated and
completed
 in whom at least one post-procedural ultrasound
follow-up examination was done and available for
analysis.

11. Exclusion criteria
 had a major stroke with no useful recovery of function
within the territory of the treatable artery
 stenosis unsuitable for stenting prior to randomisation
because of one or more of:
 Tortuous anatomy proximal or distal to the stenosis
 Presence of visible thrombus
 Proximal common carotid artery stenotic disease
 not suitable for surgery due to anatomical factors e.g. high
stenosis, rigid neck

12.  Carotid stenosis caused by non-atherosclerotic disease e.g.
dissection, fibromuscular disease or neck radiotherapy.
 Previous carotid endarterectomy or stenting in the
randomised artery
 Patients who have a life expectancy of less than two years
due to a pre-existing condition, e.g. cancer.
Exclusion criteria

13. Exclusion criteria - secondary analysis
 who did not have revascularisation
 those who underwent aborted procedures
 who crossed over to receive the alternative procedure.

14. Trial Design
 Multicenter (50 tertiary care centres in Europe, Australia,
New Zealand, and Canada)
 Open label
 randomized,
 prospective

15. Trial profile.

16. Material and methods
 Randomisation by telephone or fax using a computerised
service
 stratified by sex, age, side of stenosis and occlusion of the
contralateral carotid artery.

17. Procedures
 Carotid imaging-CTA/MRA/DSA-confirm the
diagnosis of stenosis measuring 50% or more.
 stenting complete-when a stent was placed across
the stenosis,
 endarterectomy complete- when the plaque was
removed and the arteriotomy wound closed.

18.  The duration of follow-up was initially planned for 5
years but was extended to 10 years
 carotid duplex ultrasound was to be done at every
follow-up visit.
Procedures

19. Statistical analysis
 present analysis was done per protocol
 likelihood ratio test to calculate the treatment effect p
value.
 cumulative incidence of restenosis at 1 year and 5 years
after treatment was calculated using the Kaplan-Meier
method
 the association between occurrence of restenosis and
subsequent stroke during follow-up was calculated using
Cox proportional hazards model.

20. Results
 Between May, 2001, and October, 2008, 1713 patients
were recruited to ICSS, of whom 855 were randomly
assigned to stenting and 858 to endarterectomy
 median duration of follow-up of 4·0 years and a
maximum follow-up of 10 years

21. Primary end points
 fatal or disabling stroke

22. secondary outcome
 stenosis - ≥50%- moderate , 70%-severe during follow-up

23. Baseline characteristics

24. Baseline characteristics

25.  At least moderate (=50%) restenosis occurred more
frequently in the stenting group (n=274 patients) than
in the endarterectomy
 No difference was noted between the two treatment
groups in long-term risk of severe (≥70%) carotid
restenosis or occlusion, which occurred in 10·6% of
patients in the stenting group and 8·5% of patients in
the endarterectomy
Results

26. Results
 In CAS group – no significant increase in stroke in
same or different arterial territory depending on the
presence or absence of restenosis
 In carotid endarterectomy group –increase in stroke in
same or different arterial territory in the presence
restenosis

27.  increasing the risk of restenosis (at randomisation)
 cholesterol at randomisation
 Older
 Age
 female sex,
 Current
 past smoking,
 non-insulin dependent diabetes,
 a history of angina,
 a greater extent of stenosis in the contralateral carotid artery
 raised systolic and diastolic blood pressures
 higher total serum
Results

29. Primary outcome
6.9 vs 2.5 % 5.8 vs 1.3 %7.8 vs 4.8 %

30. Discussion
 ICSS-risk of severe (≥70%) carotid restenosis, or
occlusion did not differ between treatment groups
 In this secondary analysis of ICSS, the long-term risk
of moderate (≥50%) restenosis, or occlusion of the
carotid artery, was significantly higher after stenting
 moderate (≥50%) restenosis had a significantly
increased risk of subsequent ipsilateral stroke
compared with those without restenosis.

31. Discussion
 Previous studies - stenting is associated with a greater risk
of non-disabling procedural stroke than is endarterectomy,
 The long-term efficacy at preventing recurrent stroke after
the procedural period is equivalent for each procedure.
 endovascular treatment vs endarterectomy-
 Carotid and Vertebral Artery Transluminal Angioplasty
Study (CAVATAS),
 Stent-Supported Percutaneous Angioplasty of the
Carotid Artery versus Endarterectomy (SPACE)

32. Discussion
 Independent predictors of restenosis at randomisation
 older age
 female sex (reason unknown)
 current or past smoking
 non-insulin dependent diabetes
 history of angina
 greater degree of stenosis in the contralateral carotid
artery
 higher systolic or diastolic blood pressure
 higher total serum cholesterol

33. Discussion
 the increase in stroke risk in patients with restenosis was
raised significantly after endarterectomy but not after
stenting- not significant (p>0·05)

34. Limitations
 Velocity measurements were analysed by local
investigators
 the true effect of restenosis on risk for recurrent stroke
could have been underestimated because restenosis might
only have been diagnosed after a stroke occurred or it
might only have been moderate at the time of the last
ultrasound scan and could have become severe before the
event occurred.
 No conclusions on the usefulness of regular ultrasound
follow-up after carotid revascularisation
 Did not justify repeat revascularisation in patients with
restenosis.

35. CONCLUSION
 moderate or higher (≥50%) restenosis occurred more
frequently after stenting than after endarterectomy.
 Restenosis after revascularisation of the carotid artery
increased significantly the risk for subsequent stroke.
 Risk of stroke after revascularisation with or without
restenosis is significant in CEA group and not significant in
CAS group

36. Thank You

37.  Restenosis occurring in the first 2 years after
 endarterectomy is attributed commonly to neointimal
 hyperplasia characterised by a proliferation of smooth
 muscle cells, which was thought to be associated with
 a low risk of thromboembolic events
 Restenosis
 occurring later is most likely caused by recurrent
 atherosclerosis.
In a meta-analysis of summary data from
several other
randomised trials,26 the risk of stroke was
increased
after a diagnosis of severe (≥70%) restenosis
after
endarterectomy, but not after stenting.

38. NASCET
 NASCET was established by angiographic calculation
of ICA stenosis percentage using the following
formula:
 % ICA stenosis = (1 - [narrowest ICA
diameter/diameter normal distal cervical ICA]) x 100

39.  To quantify
 the severity of stenosis, we used a cutoff for peak
systolic
 velocity in the internal carotid artery greater than
 1·3 m/s for at least moderate (=50%) stenosis and
 greater than 2·1 m/s for severe (=70%) stenosis