Table 3: Outline of interventional trials assessing treatment modalities for intracranial stenosis.

Studies/trialsInterventionsPopulationFollow upDegree of stenosisRecurrenceFatalitiesPrimary and secondary end point

WASID 2005 [49]Medical
Aspirin
569 patients (280 in Aspirin group and 289 in Warfarin group)1.8 yrs Mean50%–99% (in 50%–69% stenosis, 1 year stroke risk was 6% and in 70%–99% stenosis 19%)12% at 1 year and 19.7% at 2 years4.3%, 3.2%, 1.1%**, 3.2%®, 2.5%®®22.1%, 20.7%¥, 20.4%, 15%††, 8.9%, 23.6%***
Warfarin11% at 1 year and 17.2% at 2 years9.7%, 5.9%, 3.8%**, 8.3%®, 4.2%®®21.8%, 17.6%¥, 17%, 12.1%††, 6.2%, 24.6%***

TOSS 2005 [47] Cilostazol+Aspirin 135 (67 patients in cilostazol group and 68 patients in placebo group) 6 months 5 grades Normal Mild (signal reduction <50%)
Moderate (signal reduction >50%)
Severe (focal signal loss)
No strokes 1 subject Progression 6.7%μ
Regression 24.4%
Placebo+Aspirin1 subjectProgression 28.8%
Regression 15.4%

Marks et al. 2006 [79]Angioplasty120 patients42.3 months Mean50%–95% pre-angioplastyAnnual stroke rate 3% for territory of treatment 4.3% for any territoryDuring follow up no deaths attributable to ischemic or hemorrhagic stroke occurred3 peri-procedural strokes and 4 deaths: 5.8%
0%–90% postangioplasty Residual stenosis 59.3% had <50%, 32.4% had 50%–69% and 8.3% had >70% stenosisAt mean follow-up 2 0 . 5 ± 2 2 . 7 months 26.9% improvement in stenosis compared to post angioplasty angiogram, 49.3% unchanged, 23.9% displayed worsening stenosis

SSYLVIA 2004 [81]Bare metal stent (technical success rate 95%)61 (43 intra-cranial and 18 extracranial vertebral stenosis12 months>50%>50% stenosis at 6 months
32.4% in intracranial
42.9% in extracranial stents
None at 30 days30 day stroke rate 7.2%
1 year stroke rate 13.1% Diabetes, post procedure >30% stenosis and pretreatment vessel diameter can predict stenosis at 6 months

Wingspan (Humanitarian device exemption) study 2007 [82]Wingspan stent (flexible, self-expanding) technical success rate 97.7%45 (12 international centers)13 months50%–99%Baseline mean stenosis 74.9% post-stenting 31.9%
At 6 months 28% Restenosis rate 7.5% at 6 months
Cause mortality 2.3%30 day stroke or death rate 4.5%
Death or ipsilateral stroke rate 7.1% at 6 months
1 year rate of ipsilateral stroke and death 9.3%

National Institute of Health registry 2008 [83]Wingspan stent (post market study) technical success rate 97%129 (17 centers)5.4 months median70%–99%In-stent restenosis rate 25%Cumulative 6 month stroke death and delayed ipsilateral stroke rate 14%Periprocedural complication rates 7.5%

Bare metal balloon mounted stentsApolo stent (technical success rate 91.7%) 2007 [93]4623.9 months>50%28% at median 7.4 monthsCumulative probability of ischemic strokes in target artery territory, including any stroke and death within 30 days, was 8.8% at yrs 1-2. Among elective cases no procedure related deathsIschemic stroke rate was 4.3 per 100 patient years. 1 patient (2.2%, 1/46) developed minor ischemic stroke in the target-lesion artery territory at 6.7 months, which was related to angiographically verified restenosis
Pharos intracranial stent (technical success rate 85.75 among nonemergently treated 14 patients) 2008 [94]217.3 months median>50% with recurrent symptoms on antithrombotics
>70% poststent stenosis decreased from median 85% to 20%
No patients treated electively had recurrent symptomsMajor stroke (in-stent thrombosis 2 days after discontinuation of aspirin) in 4 patients in 30 days
Minor stroke (reversible dysarthria and paresis of the right leg) in 1 patient at discharge

International randomized trial 1985 [95]Medical therapy (Aspirin)1377 (714 assigned to best medical care and 663 with medical care+Bypass)55.8 months14% conversion from stenosis to occlusion of MCA7%–10%*30 day surgical mortality rate 0.6%Perioperative strokes in medical group 1.3%
Medical therapy+EC-IC BypassPostoperative bypass patency rate at median 32 days 96% Peri-operative
mortality rate 1.1%
4.5% in surgical group
30 day major stroke morbidity rate 2.5%

Primary end points: death, ischemic stroke, major hemorrhage, or death from vascular causes other than stroke. Secondary end points: ischemic stroke or brain hemorrhage, ischemic stroke, Ischemic stroke in territory of stenotic artery, disabling or fatal ischemic stroke, ischemic stroke, myocardial infarction, or death from vascular causes other than stroke.
Except in one case where 66% residual stenosis was left and ipsilateral stroke occurred after 7 months.
μProgression: worsening of stenosis by 1 or more grade on final MRA compared to the baseline MRA.
Regression: improvement of stenosis by 1 or more grade.
*Rate of stroke in patients with carotid siphon or MCA stenosis.
¥Ischemic stroke or brain hemorrhage.
Ischemic stroke.
††Ischemic stroke in the territory of stenotic artery.
Disabling or fatal ischemic stroke.
***Ischemic stroke, myocardial infarction, or death from vascular causes other than stroke.
Death from vascular causes.
**Death from nonvascular causes.
®Major hemorrhage.
®®Myocardial infarction.