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Stenting for Symptomatic Severe Intracranial Atherosclerotic Stenosis Does Not Improve Odds of Stroke, Death

Despite efforts to reduce perioperative complications rates by vetting of surgeons and sites, and refining patient selection, the findings nonetheless demonstrated no clinical benefit from the addition of stenting to medical therapy.

Findings from the multicenter, open-label, CASSISS clinical trial (NCT01763320) showed that the addition of percutaneous transluminal angioplasty plus stenting did not differentiate from standard care in the risk of stroke or death within 30 days in those with transient ischemic attack (TIA) or ischemic stroke because of symptomatic severe intracranial atherosclerotic stenosis (ICAS). The investigators concluded these data do not support the use of this approach in this patient population.1

Led by Peng Gao, MD, Capital Medical University, Beijing, China, the effort’s primary outcome, risk of stroke or death within 30 days of stroke in the qualifying artery territory beyond 30 days through 1 year, was not significantly different in the stenting group vs the standard medical therapy group (8.0% vs 7.2%; hazard ratio [HR], 1.10; 95% CI, 0.52-2.35; P = .82). At 3 years of follow-up, 4.4% (7 of 160) and 1.3% (2 of 159) of patients died in the stenting and medical therapy alone groups, respectively.

"Despite the efforts to improve patient selection and operator experience, the CASSISS trial redemonstrated that any potential benefit of stenting for ICAS in terms of long-term stroke prevention appears to be at least counterbalanced by the short-term procedural risk, which includes both ischemic and hemorrhagic events," Craig S. Anderson, MD, PhD, professor of neurology, UNSW Sydney, and colleagues wrote in a related editorial.2 "Although arguments can be made that the restrictive inclusion criteria inevitably led to a biased, stable, 'lower-risk’ patient group, the trial further highlights the importance of best medical management of cardiovascular risk factors, in particular, use of statins and blood pressure-lowering agents to achieve guideline recommended targets in this patient population."

The study recruited 380 patients with TIA or nondisabling, nonperforator territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset. Both groups received the same medical therapy immediately after the randomization, which included aspirin 100 mg plus clopidogrel 75 mg daily, for 90 days and control of stroke risk factors. Those randomized to stenting received the stenting with the Wingspan stent (Stryker Neurovascular) within 3 to 5 days after randomization, performed under general anesthesia.

At 2-year follow-up, findings on secondary outcomes showed no significant difference of stroke in the qualifying artery territory between the stenting and medical therapy alone groups (9.9% vs 9.0%; HR, 1.00; 95% CI, 0.56-2.10; P = .80). These findings remained consistent at 3 years for qualifying artery territory (11.3% vs 11.2%; HR, 1.00; 95% CI, 0.53-1.90; P >.99) and at 3 years for risk of disabling stroke or death (11.3% vs 9.0%; HR, 1.28; 95% CI, 0.65-2.52; P = .49). Additionally, there were no significant differences in the rate of 3-year risk of death (4.4% vs 1.3%; HR, 3.75; 95% CI, 0.77-18.13; P = .08) or cumulative 3-year risk of any stroke, TIA, or cardiovascular event (14.2% vs 18.0%; HR, 0.76; 95% CI, 0.45-1.30; P = .31) between the groups.

In post hoc analyses, the 30-day rate of stroke or death was 5.1% in the stenting group and 2.2% in the medical group alone. In the stenting group, there were 5 ischemic strokes within 30 days, all of which were considered ultimately disabling but not fatal, and 4 hemorrhagic strokes, 2 of which were fatal. In the medical therapy alone group, there were 4 ischemic strokes within 30 days, 2 of which were ultimately disabling, and no hemorrhagic strokes within 30 days. For patients qualified with TIA, the rate of primary outcome was 5.7% in the stenting group and 5.3% in the medical therapy alone group.

There have been several other attempts to try to find effective treatments for patients with ICAS. Recently, in a subanalysis of the RESCUE-BT trial, treatment with tirofiban prior to endovascular thrombectomy did not impact disability for those with acute ischemic stroke; however there was a more favorable point estimate among the large artery atherosclerosis subgroup.3

"Although the prognosis from ICAS will vary according to age, background risk factors, and the effectiveness of medical management, the evidence generated from these 2 trials are broadly generalizable," Anderson et al referenced.2 "Moreover, these studies demonstrate the substantial advances being made by investigators in China, with input from experts in the US, in the conduct of multicenter randomized clinical trials and strengthen the importance of such evidence in guiding health policy and practice in this vast country where stroke has an enormous health, economic, and social toll."

REFERENCES
1. Gao P, Wang T, Wang D, et al. 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 Neurol. 2022;328(6):534-542. doi:10.1001/jama.2022.12000.
2. Anderson CS, Song L, Liu J. Therapeutic strategies for intracranial atherosclerosis. JAMA Neurol. 2022;328(6):529-531. doi:10.1001/jama.2022.11525.
3. RESCUE-BT trial investigators. Effect of intravenous tirofiban vs placebo before endovascular thrombectomy on functional outcomes in large vessel occlusion stroke: the RESCUE-BT randomized clinical trial. JAMA Neurol. 2022;328(6):543-553. doi:10.1001/jama.2022.12584