ICAD Endovascular management

1. ICAD: Recent advances on
endovascular management
Dr Ashwin Lathiya
SR Neurology
GMC Kota

2. Stroke. 2020;51:e49-e53. 2

3. Introduction
• Common etiology of cerebrovascular disease
• Responsible for at least 9% of all ischemic strokes (Sacco et al., 1995).
• Risk of recurrent stroke of approximately 15% per year without treatment.
• Risk factors for symptomatic and asymptomatic ICAD include age, Asian and
black race, hypertension, diabetes mellitus, hyperlipidemia, metabolic
syndrome, sedentary lifestyle, and smoking.
• Mechanisms of stroke in ICAD: artery-to-artery embolization, perforator
disease, and impaired distal perfusion.
Neurosurgery 86:755–762, 2020 3

4. Medical
Treatments
Intracranial Atherosclerosis Treatment
Past, Present, and Future. Flusty B at al.Stroke. 2020;51:e49–e53
4
Antithrombotic Therapy
Risk Factor Modification
Lipid-Lowering Treatments
Targeting the Inflammatory Cascade

5. Medical Treatments
• Antithrombotic Therapy
Intracranial Atherosclerosis Treatment
Past, Present, and Future. Flusty B at al.Stroke. 2020;51:e49–e5
5
Lipid-Lowering
Treatments
Risk Factor
Modification
Targeting the
Inflammatory
Cascade
• Aspirin
• WASID
• CHANCE 1) Smoking cessation,
2) Adequate physical
activity,
3) Implementation of
healthy dietary habits.
Blood pressure goal <140/90
mm Hg; <130/80 if diabetic
LDL <70 mg/dL
SPARCL trial (Stroke
Prevention by
Aggressive Reduction
in Cholesterol Levels),
atorvastatin 80 mg
daily vs placebo
• IL- 6
• CANTOS trial
• COLCOT

6. Stroke. 2021;52:e364–e467. 6

7. What next?
• Although unproven, therapies of last resort for patients who have recurrent
ischemic stroke due to ICAD despite maximal medical therapy include
endovascular stenting or submaximal angioplasty.
• Intracranial arterial stenting and other interventional procedures are not
recommended for patients with a first stroke or TIA attributable to severe
intracranial artery stenosis, since results from the SAMMPRIS and VISSIT
trials showed that medical management was superior to intracranial
stenting.
7

8. Three different mechanisms of ischemic stroke in intracranial
atherosclerosis.
Luo J, Wang T, Gao P, Krings T an Jiao L (2018) Endovascular Treatment of Intracranial Atherosclerotic Stenosis: Current Debates and Future
Prospects. Front Neurol. 9:666
8
(A) Artery to artery embolism,
(B) Local perforator
ischemia,
(C) Hemodynamic
hypoperfusion.

9. Infarct patterns for underlying stroke mechanisms
• Perforator pattern: infarct in the subcortical or perforator territory, i.e., in
the territory perfused by perforating vessels that originate at the site of
stenosis.
• Arterial embolic pattern: infarct in the downstream territory of the
stenotic vessel (cortical, subcortical, or both) and is limited to the territory
supplied by a single intracranial culprit artery.
• Border-zone or hemodynamic: one or more infarct lesions located in the
internal border-zone region in the corona radiata or centrum semiovale
and/or in the cortical border-zone region, between MCA and ACA or
between MCA and PCA.
Luo J, Wang T, Gao P, Krings T an Jiao L (2018) Endovascular Treatment of Intracranial Atherosclerotic Stenosis: Current Debates and Future Prospects.
Front Neurol. 9:666
9

10. What to choose?
Luo J, Wang T, Gao P, Krings T an Jiao L (2018) Endovascular Treatment of Intracranial Atherosclerotic Stenosis: Current Debates and Future Prospects.
Front Neurol. 9:666
10
Patients with hypoperfusion or poor collateral circulation
of the downstream territory at the stenotic arteries may
benefit more from endovascular treatment
Patients with perforator occlusion will have no benefit
(or may even be harmed) from angioplasty.
Patients with artery-artery embolism may benefit from
aggressive medical management.

11. Vessel wall imaging-HR MRI
Kim JS, Caplan LR, Wong KS (eds): Intracranial Atherosclerosis: Pathophysiology, Diagnosis and Treatment. Front Neurol Neurosci.
Basel, Karger, 2016, vol 40, pp 109–123
11

12. Endarterectomy
Barnard ZR, Alexander MJ Update in the treatment of intracranial
atherosclerotic disease Stroke and Vascular Neurology 2020 12
Early surgical therapy for ICAD
was pioneered by Sundt et al:
open surgical endarterectomy
of cerebral arteries.
Cerebral arteries amenable to
endarterectomy ranged from 2
to 4 mm, so technically this
was a challenging procedure.

13. Extracranial-intracranial (EC-IC) bypass
• Direct with
• superficial temporal artery (STA)
• radial artery graft
• saphenous vein graft
• The prospective randomised EC-IC bypass trial,
comparing direct bypass with the STA versus
medical therapy for patients with symptomatic
cerebral atherosclerotic disease with either
total occlusion or high-grade stenosis, failed to
show a benefit with surgery.
• COSS
• Indirect
• Encephaloduroarteriosynangiosis (EDAS),
transposing the STA adjacent to the
cortical middle cerebral artery branches
• ERSIAS (Surgical Indirect
Revascularization for Symptomatic
Intracranial Arterial Stenosis): gradual
neovascularisation of the ischemic
territory through angiogenesis from
the donor artery, undergoing.
Barnard ZR, Alexander MJ. Update in the treatment of intracranial atherosclerotic
disease. Stroke & Vascular Neurology 2020 13

14. Recommendations
Stroke. 2021;52:e364–e467 14

15. Surgical or
Endovascular
Treatments
• Balloon angioplasty alone
• Balloon-mounted stent (Pharos Vitesse)
• Self-expandable stents (Wingspan)
Luo J, Wang T, Gao P, Krings T and Jiao L (2018) Endovascular Treatment of Intracranial
Atherosclerotic Stenosis: Current Debates and Future Prospects. Front. Neurol. 9:666. 15

16. Endovascular therapy: balloon angioplasty

17. Endovascular therapy: balloon angioplasty
17
 Thin Muscularis layer
 Lack external elastic layer
 Angioplasty alone in cerebral arteries has often resulted in arterial recoil and restenosis,
requiring subsequent repetitive treatments.
 More recent use of drug-coated balloons for treatment of ICAD remains controversial.

18. Endovascular
therapy:
submaximal
angioplasty
Stapleton CJ, Chen YF, Shallwani H, et al. Submaximal Angioplasty for Symptomatic Intracranial Atherosclerotic Disease: A Meta-Analysis of Peri-Procedural
and Long-Term Risk. Neurosurgery. 2020;86(6):755-762.
18
 To qualify as
“submaximal,” the
angioplasty balloon had
to be undersized by at
least 0.5 mm or sized to
approximately 50% to
80% of the normal vessel
diameter.

19. Seyedsaadat SM, et al. J NeuroIntervent Surg 2019;0:1–6 19

20. Endovascular therapy: Intracranial stenting
First stent --balloon-expandable stent that was fairly successful in the SSYLVIA clinical
trial (Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries),
but was never manufactured and marketed subsequently.
The Wingspan stent was the first self-expanding stent: only (FDA)-approved stent for
the treatment of symptomatic intracranial ICAD.
Initial Humanitarian Device Exemption (HDE) approval trial treated 44 patients with
the stent and demonstrated excellent periprocedural safety results, with a 4.5%
complication rate, and this was subsequently marketed under the HDE application.
Luo J, Wang T, Gao P, Krings T and Jiao L (2018) Endovascular Treatment of
Intracranial Atherosclerotic Stenosis: Current Debates and Future Prospects. Front.
Neurol. 9:666.
20

21. Endovascular therapy
Balloon-mounted stent (Pharos Vitesse)
• Coronary stents
• Not designed for intracranial vasculature & difficult to deliver through
the tortuous cervical and intracranial vasculature.
• led to traumatic injury
• INTRASTENT registry study: balloon-mounted stents vs self-expandable
stents
 No statistically significant difference in complication rates
 Balloon-expandable stent-Prone to a higher risk of perforator strokes
 Self-expandable stent -tended to result in more thromboembolic events
Luo J, Wang T, Gao P, Krings T and Jiao L (2018) Endovascular Treatment of Intracranial Atherosclerotic Stenosis: Current
Debates and Future Prospects. Front. Neurol. 9:666.
21

22. Stroke. 2007;38:881-887 22

23. PHAROS Vitesse balloon-expandable neurovascular stent system.
Zaidat OO, Castonguay AC, Fitzsimmons BF, et al. Design of the Vitesse Intracranial Stent Study for Ischemic Therapy (VISSIT) trial in
symptomatic intracranial stenosis. J Stroke Cerebrovasc Dis. 2013;22(7):1131-1139. 23

24. Self-Expandable Stent (Wingspan stent)
 More flexible and passes the tortuous intracranial
vasculature more easily than balloon-mounted
systems
 Higher technical success rate
 Lower risk of perforator infarctions, bcz the
angioplasty can be undersized
• Disadvantage:
 Two-step maneuver may lengthen procedure
duration, which potentially increases the risk of
embolic stroke
 Exchange wire maneuver may increase the risk of
subarachnoid hemorrhage due to inadvertent
and uncontrolled movement of guide-wire tip
Luo J, Wang T, Gao P, Krings T and Jiao L (2018) Endovascular Treatment of Intracranial
Atherosclerotic Stenosis: Current Debates and Future Prospects. Front. Neurol. 9:666.
24

25. Early stenting trial
• Two subsequent registries, each enrolling over 150
patients with the delivery of Wingspan stents, US
Wingspan stent registry and the NIH Wingspan stent
registry: demonstrated approximately 6%
periprocedural complication rate.
25

26. SAMMPRIS trial
• Multicenter, prospective, RCT of intracranial stenting for ICAD
• Aim: compare the efficiency of recurrent stroke prevention b/w percutaneous
transluminal angioplasty and stenting (PTAS) with aggressive medical management vs.
aggressive medical management alone.
• Included: symptomatic patients with recent (i.e., within 30 days) TIA or non-disabling
stroke + having 70–99% stenosis of a major intracranial artery.
• Initial design was to recruit 764 patients
• Trial was halted early because of the unexpected result of a 30 days death or stroke rate
of 14.7% (10.2% ischemic and 4.5% hemorrhagic) in the PTAS group, compared with 5.8%
in the medical management group
Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J
Med. 2011;365(11):993-1003. 26

27. SAMMPRIS trial
results
Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical
therapy for intracranial arterial stenosis. N Engl J Med. 2011;365(11):993-1003. 27
Short-term safety of medical management was superior
to PTAS in the patients treated in this trial.
long-term efficacy of medical management in the
SAMMPRIS trial was also superior to PTAS, with 1, 2, and
3 years rates of mortality or stroke of 12.6, 14.1, and
14.9% in the medical management group compared to
19.7, 20.6, and 23.9% in the PTAS group, respectively.
FDA subsequently mandated a postmarketing
surveillance study of the Wingspan stent, following the
poor SAMMPRIS results.

28. The WEAVE trial
• The WEAVE trial (Wingspan Stent System Post Market Surveillance) was
designed to determine the safety of the stent when used strictly
on-label by experienced interventionalists.
• Enrolled 152 on-label patients, which was the largest on-label trial performed in
the USA to date, and excellent results were seen. The periprocedural
complication rate of 2.6% was also the lowest complication rate obtained in prior
trials.
Alexander MJ, Zauner A, Chaloupka JC, et al. WEAVE
Trial: Final Results in 152 On-Label Patients. Stroke.
2019;50(4):889-894.
28

29. The WOVEN trial: Wingspan One-year Vascular Events and neurologic
outcomes
Alexander MJ, Zauner A, Gupta R, et al The WOVEN trial: Wingspan One-year Vascular Events and Neurologic Outcomes Journal of NeuroInterventional
Surgery 2021;13:307-310. 29
 WEAVE trial assessed 152 patients stented
with the Wingspan stent strictly by its current
on-label indication and found a 2.6%
periprocedural stroke and death rate.
 WOVEN study assesses the 1-year
follow-up from this cohort

30. On-label criteria for Wingspan stent
Age 22 to 80 years,
Symptomatic intracranial atherosclerotic stenosis of 70% to 99%,
Baseline modified Rankin Scale score ≤3,
≥2 strokes in the vascular territory of the stenotic lesion with at least 1 stroke while
on medical therapy,
Stenting of the lesion ≥8 days after the last stroke.
Alexander MJ, Zauner A, Chaloupka JC, et al. WEAVE Trial: Final Results in 152 On-Label Patients. Stroke. 2019;50(4):889-894. 30

31. Mori
classification
for types of
stenoses
Luo J, Wang T, Gao P, Krings T an Jiao L (2018) Endovascular Treatment of Intracranial Atherosclerotic Stenosis:
Current Debates and Future Prospects. Front Neurol. 9:666 31
Mori A, a short and concentric
lesion with a short length (<5 mm)
Mori B, a tubular or extreme
eccentric lesion with intermediate
length (between 5 and 10 mm)
Mori C, a diffuse lesion with a long
length (>10 mm)

32. Choice according to Mori class
Balloon-mounted stents are suitable for patients with smooth arterial
access and Mori A lesions, mid basilar artery, and distal M1 segment
lesions
Self-expanding stents may be suitable for patients with tortuous
arterial access and Mori B or C lesions
Balloon angioplasty alone is suitable for patients with tortuous arterial
access with Mori A lesions and a small target-vessel diameter of <2.5
mm
Luo J, Wang T, Gao P, Krings T an Jiao L (2018) Endovascular Treatment of Intracranial Atherosclerotic Stenosis: Current Debates and
Future Prospects. Front Neurol. 9:666

33. Major Wingspan stent trials with mean time to treatment and
complication rates
33
Barnard ZR, Alexander MJ. Update in the treatment of intracranial atherosclerotic disease. Stroke & Vascular Neurology 2020;5: e000279

34. Stroke. 2021;52:e364–e467 34

35. Stroke. 2021;52:e364–e467 35

36. Take home
message
• Endovascular treatment in
carefully selected patients,
individualized choice of
endovascular treatment
subtypes, and an experienced
multidisciplinary team managing
the patient in the pre-, peri- and
post-procedural period have the
potential to provide safe an
efficacious treatment of patients
with symptomatic ICAD.
36

37. References
Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy
for intracranial arterial stenosis. N Engl J Med. 2011;365(11):993-1003.
Alexander MJ, Zauner A, Chaloupka JC, et al. WEAVE Trial: Final Results in 152 On-
Label Patients. Stroke. 2019;50(4):889-894.
Luo J, Wang T, Gao P, Krings T an Jiao L (2018) Endovascular Treatment of Intracranial
Atherosclerotic Stenosis: Current Debates and Future Prospects. Front Neurol. 9:666.
Barnard ZR, Alexander MJ.Update in the treatment of intracranial atherosclerotic disease.Stroke
and Vascular Neurology 2020.
Stapleton CJ, Chen YF, Shallwani H, et al. Submaximal Angioplasty for Symptomatic Intracranial
Atherosclerotic Disease: A Meta-Analysis of Peri-Procedural and Long-Term Risk. Neurosurgery.
2020;86(6):755-762.
Intracranial Atherosclerosis Treatment Past, Present, and Future. Flusty B at al.Stroke.
2020;51:e49–e5.
Jafari M, Nguyen TN, Ortega-Gutierrez S, et al. Current Advances in Endovascular
Treatment of Intracranial Atherosclerotic Disease and Future Prospective. J Stroke
Cerebrovasc Dis. 2021;30(3):105556
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38. Thank you
38