title: Future directions for intra-arterial therapy for acute ischaemic stroke: is there life after three negative randomized controlled studies?
abstract: BACKGROUND
  The three randomised controlled trials, Interventional Management of Stroke III (IMS3), Mechanical Retrieval and Revascularization of Stroke Clots Using Embolectomy (MR RESCUE) and Synthesis Expanasion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischaemic Stroke (SYNTHESIS EXP) showed no significant difference in clinical outcomes comparing intra-arterial (IA) therapy with intravenous thrombolysis. This article will explore the reasons for failure to show superiority of IA therapy.
  
  
  CONCLUSIONS
  There are many reasons for the disappointing results of the three randomised controlled trials. Opposing views on IA therapy exist. Critics argue that only a small percentage of patients will be eligible for IA therapy and that it will never be cost-effective. Additionally, current trials have failed to address superior recanalization rates of new generation devices and lack of patient selection by advanced imaging. Time-to-treatment is longer in these randomised controlled trials and stroke outcomes were worse than anticipated. The current randomised controlled trials also took long periods to complete. There is emerging evidence that general anesthetic negatively influences outcome. Next generation trials will attempt to address these issues. Key Messages: There are disparate explanations for the disappointing results from the three IA therapy randomized controlled studies. Poor recanalisation rates with first generation endovascular devices, lack of advanced neuroimaging to aid in patient selection, lack of data surrounding the use of general anaesthesia, and prolonged time-to-treatment are potential contributors to negative results. The new generation of trials has the potential of addressing these pressing issues.
authors.affiliation: Melbourne Brain Centre, Department of Radiology, Royal Melbourne Hospital, Melbourne, Vic., Australia.
authors.forename: Julian
authors.initials: J
authors.lastname: Maingard
authors.affiliation: Melbourne Brain Centre, Department of Radiology, Royal Melbourne Hospital, Melbourne, Vic., Australia ; Neurointervention Service, Department of Radiology, Royal Melbourne Hospital, Melbourne, Vic., Australia.
authors.forename: Bernard
authors.initials: B
authors.lastname: Yan
keywords: Acute ischaemic stroke; Intra-arterial therapy; Intravenous thrombolysis; Recanalization success