Authors: Christine Tunkl, MD

Twitter: @ChrissiTunkl

Neurology Department, University Hospital Heidelberg

Atherosclerotic stenosis accounts for a high proportion of ischemic stroke and can challenge us as treating physicians. Strokes caused by intracranial stenosis have a high risk of recurrence, so we might be tempted to treat those patients with percutaneous transluminal angioplasty and stenting (PTAS). Of course, every patient with intracranial atherosclerotic stenosis receives best medical treatment (BMT) – consisting of (dual) antiplatelet therapy, blood pressure management and lipid-lowering therapy1. But should patients with symptomatic intracranial stenosis also be treated with stenting or not?

None of the previous trials (VISSIT2, SAMMPRIS3) could prove a benefit of additional stenting compared to BMT. SAMMPRIS3 was even terminated earlier because stenting proved harmful in terms of a higher 30-day rate of stroke or death (14.7%) in the intervention group compared to in the medical-management group (5.8%). Still, it seems we were not convinced about the superiority of BMT and it was time for another randomized, controlled trial4 to prove what other trials and guidelines had suggested before:  that there doesn’t seem to be a benefit in adding percutaneous transluminal angioplasty and stenting to BMT in patients with symptomatic intracranial atherosclerotic stenosis.

The recently published CASSISS Trial4 enrolled a total of 380 patients and randomized them 1:1 either into the best medical treatment arm versus best medical treatment combined with stenting. Recruited were patients with TIA or nondisabling ischemic stroke (modified Rankin Scale score, 0-2) and severe stenosis (degree of stenosis: 70%-99%) of a major intracranial artery supplying the territory of the ischemic event. The primary outcome, risk of stroke or death within 30 days or stroke in the respective vascular territory within one year, was not significantly different (stenting 8.0% vs medical 7.2%; HR, 1.10 [95% CI, 0.52-2.35]; P = 0.82). In addition, the investigators did not observe a significant difference in the risk of recurrent stroke or death within three years. Why is that? The authors of the trial discuss that periprocedural complications caused by guidewire perforation of arteries and disturbances of vulnerable, atherosclerotic plaque may lead to the lack of superiority of stenting. It goes without saying that this technically challenging procedure requires a high level of experience.

The CASSISS Trial together with previous trials is highly relevant, as we are faced with symptomatic intracranial atherosclerotic stenosis often in our clinical practice.

The CASSISS trial will now further strengthen the ESO’s recommendation that best medical treatment should be favored over stenting for patients with symptomatic intracranial atherosclerotic stenosis4.


1 – Psychogios M, Brehm A, López-Cancio E, Marco De Marchis G, Meseguer E, Katsanos AH, Kremer C, Sporns P, Zedde M, Kobayashi A, Caroff J, Bos D, Lémeret S, Lal A, Arenillas JF. European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease. Eur Stroke J. 2022 Sep;7(3):III-IV.

2 – Zaidat OO, Fitzsimmons BF, WoodwardBK, et al; VISSIT Trial Investigators. Effect of a balloon-expandable intracranial stent vs medical therapy on risk of stroke in patients with symptomatic intracranial stenosis. JAMA. 2015;313 (12):1240-1248. doi:10.1001/jama.2015.1693

3 – Chimowitz MI, Lynn MJ, Derdeyn CP, et al; SAMMPRIS Trial Investigators. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365(11):993-1003.

4- Gao P, Wang T, Wang D, Liebeskind DS, Shi H, Li T, Zhao Z, Cai Y, Wu W, He W, Yu J, Zheng B, Wang H, Wu Y, Dmytriw AA, Krings T, Derdeyn CP, Jiao L; CASSISS Trial Investigators. Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis: The CASSISS Randomized Clinical Trial. JAMA. 2022 Aug 9;328(6):534-542.