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Intracranial angioplasty again failed for less severe intracranial atherosclerotic stenosis (ICAS) strokes in a Chinese trial. However, a separate analysis did leave a glimmer of hope that IV antiplatelet therapy prior to thrombectomy helped eligible candidates with ICAS.

Echoing the results of prior trials, patients in the CASSISS trial presenting with transient ischemic attack (TIA) or nondisabling stroke gained no benefit in terms of prevention of future events, reported Liqun Jiao, MD, of China's Xuanwu Hospital and Capital Medical University in Beijing, and colleagues.

Adding stenting to medical therapy didn't reduce the primary outcome of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year (8.0% vs 7.2% after medical therapy alone, HR 1.10, 95% CI 0.52-2.35).

ICAS is a major cause of stroke that disproportionately affects Black, Asian, and Hispanic people at relatively younger ages. Stroke survivors with ICAS are at greater risk of recurrent events, so the 380-person , published in JAMA, had been designed to improve stenting's chances of succeeding in this population.

"Despite efforts to reduce perioperative complication 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 for the treatment of patients with symptomatic severe intracranial atherosclerotic stenosis," Jiao's group concluded.

This conclusion was bolstered by similarly neutral findings in secondary endpoints, including stroke in the qualifying artery territory at 2 years and 3 years. What's more, mortality rates at 3 years even put the stenting group at a numerical disadvantage, albeit not statistically significant (4.4% vs 1.3%, HR 3.75, 95% CI 0.77-18.13).

Negative results also came from the trial of IV tirofiban (Aggrastat) given right before endovascular therapy for large vessel occlusion, according to findings previously presented at the International Stroke Conference and now published in JAMA as well.

In the trial, also from China, tirofiban didn't reduce disability at 90 days by modified Rankin Scale score compared with placebo. Nor was there any advantage for the highly selective nonpeptide platelet glycoprotein IIb/IIIa inhibitor on any secondary endpoints after thrombectomy, reported Qingwu Yang, MD, PhD, of Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University of Chongqing, China, and colleagues.

The investigators said their findings do not support IV tirofiban before endovascular thrombectomy for acute ischemic stroke with one possible exception.

"In subgroup analyses, the point estimates for tirofiban vs placebo raise the possibility that tirofiban might be associated with lower disability level among patients with stroke due to large artery atherosclerosis, although the test for interaction did not reach statistical significance," according to Yang and colleagues. They said a confirmatory trial is merited in this population.

An led by Craig Anderson, MD, PhD, of The George Institute for Global Health in Sydney, Australia, observed that most of the RESCUE BT cohort with large artery atherosclerosis had ICAS.

"[A]ny further investigation of targeted approaches with tirofiban, or other potent antiplatelet agent(s), in ICAS would benefit from a better understanding of the interactions between atherosclerosis and thrombosis, the importance of thrombus composition ... and the relation of blood flow to vascular occlusion in the progression of large vessel occlusion in acute ischemic stroke," Anderson's group wrote.

Tirofiban is currently only for the treatment of acute coronary syndrome. In stroke, the antiplatelet has a mixed body of evidence. Yang's team noted that yet another Chinese trial, the ongoing , is investigating the outcomes of tirofiban in non-large-vessel occlusive stroke.

Both Jiao and Yang's groups cautioned that their respective studies may have limited generalizability to populations outside China.

Yet the editorialists suggested this may not be the case.

"Despite relatively long workflow times and low use of intravenous thrombolysis, outcomes from endovascular procedures in China are comparable to Western countries. Although the prognosis from ICAS will vary according to age, background risk factors, and the effectiveness of medical management, the evidence generated from these two trials are broadly generalizable," Anderson and colleagues argued.

CASSISS had 358 people eligible for the main analysis (mean age 56.3 years, 73.5% men). Eligible people had TIA or nondisabling, nonperforator territory ischemic stroke attributed to severe intracranial stenosis (70%-99% occlusion). Excluded were patients with ischemic symptoms within 3 weeks of study enrollment. Randomization resulted in well-balanced stenting and control group characteristics.

RESCUE BT included 948 thrombectomy candidates randomized after presenting within 24 hours of time last known well (mean age 67 years, 41.2% women). Tirofiban and placebo recipient characteristics were well balanced. The tirofiban group received the study drug as a bolus dose of 10 μg/kg, followed by continuous infusion of 0.15 μg/kg/min for up to 24 hours.