Discussion
death, sICH, intracranial hemorrhage, stroke, cardioembolic, hemorrhagic transformation, infarcts, ischemic stroke, hemorrhage, LAA stroke, artery atherosclerotic disease, acute ischemic stroke
INTRACRANIAL HEMORRHAGE, STROKE, ISCHEMIC STROKE, HEMORRHAGE, SECONDARY
This study focused on the population of patients with acute ischemic stroke due to intracranial large artery atherosclerotic disease, which is a main cause of stroke in Asian patients and a determinant of poor outcome. Randomized studies evaluating the outcome of EVT in patients with intracranial LAA were sparse. Among intracranial LAA patients with successful reperfusion (eTICI 2b50‐3), periprocedural intravenous tirofiban treatment was associated with improved functional outcome at 90 days, and rates of death and sICH were comparable between the two groups. The magnitude of treatment effect was sizable, with the number needed to treat for one more functional independent outcome at 90 days of 9.7. Due to the post hoc secondary analysis design and limited size of successful population, all of the results were exploratory.In the overall RESCUE BT trial, mechanisms of qualifying ischemic stroke were LAA in 45.9%, cardioembolic in 42.8%, other in 2.3%, and unknown in 8.1% and tirofiban was associated with improved outcomes only in the LAA patients.Intriguingly, among LAA patients there was evidence of heterogeneity of treatment effect across different eTICI reperfusion levels. Tirofiban was associated with improved outcomes among patients with substantial reperfusion (eTICI 2b50), but no statistically significant effect was seen for patients with excellent (eTICI 2c) or complete (eTICI 3) reperfusion. This observation supports a role for tirofiban in resolving or stabilizing residual microcirculatory obstructions angiographically visible in distal fields at the end of the thrombectomy procedure. Conversely, this finding suggests that an effect of tirofiban upon microcirculatory reperfusion is less marked or absent.Among LAA patients with successful reperfusion, intravenous tirofiban was associated with an increased rate of any radiologic intracranial hemorrhage but not symptomatic intracranial hemorrhage or mortality. This finding suggests that the antiplatelet effect of intravenous tirofiban may increase rates of any hemorrhagic transformation of bland infarcts but may not predispose to major hemorrhage to the same degree. In addition, the extended EVT treatment time window may have contributed to increased rates of intracranial hemorrhage in both treatment groups in the current study.The strengths of our study included the large‐scale, double‐blind, and placebo‐controlled design. This study also has several limitations. First, it was a post hoc analysis, multiple testing may increase the risk of Type I errors. All the results should be interpreted with caution. Second, only Chinese patients with LAA stroke were enrolled in the trial, which may reduce the generalizability of study findings. Third, the selection for patients in the extended therapeutic window was based on ASPECTS score according to non‐contrast CT scan rather than CT perfusion assessment, as automated CT perfusion analysis software was not available in many of participating hospitals due to high cost. Fourth, end‐of‐procedure reperfusion grade is an early post‐randomizing rather than baseline patient characteristics, necessitating caution regarding subgroup findings. However, study treatment on average was started coincident with, not before, arterial puncture and only a small fraction of treatment agent was administered before reperfusion grade was assessed. Fifth, analyses are generally more statistically powerful when continuous measures are used rather than dichotomies in the subgroup analysis. Interpretation of the results should be more cautious.