Intracranial Atherosclerotic Disease

Table 3

Outline of interventional trials assessing treatment modalities for intracranial stenosis.

Studies/trials	Interventions	Population	Follow up	Degree of stenosis	Recurrence	Fatalities	Primary and secondary end point
WASID 2005 [49]	Medical; Aspirin	569 patients (280 in Aspirin group and 289 in Warfarin group)	1.8 yrs Mean	50%–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 years	4.3%, 3.2%^∞, 1.1%**, 3.2%^®, 2.5%^®®	22.1%^†, 20.7%^¥, 20.4%^∧, 15%^††, 8.9%^¶, 23.6%***
	Warfarin				11% at 1 year and 17.2% at 2 years	9.7%, 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+Aspirin					1 subject	Progression 28.8%; Regression 15.4%
Marks et al. 2006 [79]	Angioplasty	120 patients	42.3 months Mean	50%–95% pre-angioplasty	Annual stroke rate 3% for territory of treatment 4.3% for any territory	During follow up no deaths attributable to ischemic or hemorrhagic stroke occurred	3 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% stenosis			At mean follow-up 20.5±22.7 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 stenosis	12 months	>50%	>50% stenosis at 6 months; 32.4% in intracranial; 42.9% in extracranial stents	None at 30 days	30 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 months	50%–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 median	70%–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 stents	Apolo stent (technical success rate 91.7%) 2007 [93]	46	23.9 months	>50%	28% at median 7.4 months	Cumulative 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 deaths	Ischemic 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]	21	7.3 months median	>50% with recurrent symptoms on antithrombotics; >70% poststent stenosis decreased from median 85% to 20%	^‡No patients treated electively had recurrent symptoms		Major 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 months	14% conversion from stenosis to occlusion of MCA	7%–10%*	30 day surgical mortality rate 0.6%	Perioperative strokes in medical group 1.3%
	Medical therapy+EC-IC Bypass			Postoperative 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.