Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis

Abstract

Prior randomized trials have generally shown harm or no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis, but it remains uncertain as to whether refined patient selection and more experienced surgeons might result in improved outcomes.OBJECTIVE To compare stenting plus medical therapy vs medical therapy alone in patients with symptomatic severe intracranial atherosclerotic stenosis. DESIGN, SETTING, AND PARTICIPANTSMulticenter, open-label, randomized, outcome assessor-blinded trial conducted at 8 centers in China. A total of 380 patients with transient ischemic attack or nondisabling, nonperforator (defined as nonbrainstem or non-basal ganglia end artery) territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset were recruited between March 5, 2014, and November 10, 2016, and followed up for 3 years (final follow-up: November 10, 2019).INTERVENTIONS Medical therapy plus stenting (n = 176) or medical therapy alone (n = 182). Medical therapy included dual-antiplatelet therapy for 90 days (single antiplatelet therapy thereafter) and stroke risk factor control. MAIN OUTCOMES AND MEASURESThe primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. There were 5 secondary outcomes, including stroke in the qualifying artery territory at 2 years and 3 years as well as mortality at 3 years. RESULTS Among 380 patients who were randomized, 358 were confirmed eligible (mean age, 56.3 years; 263 male [73.5%]) and 343 (95.8%) completed the trial. For the stenting plus medical therapy group vs medical therapy alone, no significant difference was found for the primary outcome of risk of stroke or death (8.0% [14/176] vs 7.2% [13/181]; difference, 0.4% [95% CI, −5.0% to 5.9%]; hazard ratio, 1.10 [95% CI, 0.52-2.35]; P = .82). Of the 5 prespecified secondary end points, none showed a significant difference including stroke in the qualifying artery territory at 2 years (9.9% [17/171] vs 9.0% [16/178]; difference, 0.7% [95% CI, −5.4% to 6.7%]; hazard ratio, 1.10 [95% CI, 0.56-2.16]; P = .80) and 3 years (11.3% [19/168] vs 11.2% [19/170]; difference, −0.2% [95% CI, −7.0% to 6.5%]; hazard ratio, 1.00 [95% CI, 0.53-1.90]; P > .99). Mortality at 3 years was 4.4% (7/160) in the stenting plus medical therapy group vs 1.3% (2/159) in the medical therapy alone group (difference, 3.2% [95% CI, −0.5% to 6.9%]; hazard ratio, 3.75 [95% CI, 0.77-18.13]; P = .08).CONCLUSIONS AND RELEVANCE Among patients with transient ischemic attack or ischemic stroke due to symptomatic severe intracranial atherosclerotic stenosis, the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The find...

Comparative effect of stenting plus medical therapy vs medical therapy alone on the risk of stroke and death in patients with symptomatic intracranial stenosis: a systematic review and meta-analysis

“…Recently, an RCT reported Fig. 2 Forest plots for primary outcomes by Gao et al systematically compared stenting plus medical therapy with medical therapy alone [22]. Consistent with their findings, our meta-analysis results showed that the effect of stenting plus medical therapy on the risk of stroke and death was not inferior to that of medical therapy alone in the long term.…”

Recurrent stroke risk in intracranial atherosclerotic disease

“…These findings were challenged with the results of the SAMMPRIS and VISSIT trials which showed significantly higher rates of stroke with angioplasty and stenting compared to dual antiplatelet therapy, shaping national guidelines which endorse aggressive medical therapy and advise against endovascular treatment in this population (5,7,8). Furthermore, the more recent CASSISS trial showed no benefit of angioplasty and stenting compared to aggressive medical management, further validating current recommendations (9). None of these trials, however, riskstratified patients based on hemodynamics or thromboembolic potential, relying exclusively on luminal stenosis as major entry criteria.…”

“…The recently published CASSISS trial limited enrollment of patients to beyond 3 weeks after their index event and found no difference in stroke recurrence between endovascular and medically treated patients. Both groups, however, had significantly lower rates of stroke recurrence compared to historical controls (5, 7), likely in part due to later enrollment (9). In summary, both the risk of recurrent ischemic stroke and periprocedural stroke appears to be highest in the early period after an index stroke, and therefore the risks of each must be weighed carefully in real-world treatment decisions and in the design of future prospective studies.…”

Effects of stent shape on focal hemodynamics in intracranial atherosclerotic stenosis: A simulation study with computational fluid dynamics modeling

“…Stenting currently is not a first-line treatment for patients with symptomatic ICAS, with higher stroke and mortality rates compared with medical treatment alone in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial published in 2011 ( 25 ), and similar stroke and mortality rates with medical treatment in the most recent China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial ( 26 ). In addition to the concern over peri-procedural complications, which has been significantly reduced in recent studies with refined patient eligibility criteria and more experienced interventionalists, ISR is also a concern or a marker of treatment failure.…”