Collateral lessons from recent acute ischemic stroke trials

Abstract

Numerous acute ischemic stroke trials have recently published detailed results, providing an opportunity to consider the role of collaterals in stroke pathophysiology and their influential effect on patient outcomes. Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS), the largest randomized controlled trial of device therapy to date, tested the potential augmentation of collateral perfusion. SYNTHESIS Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), and Interventional Management of Stroke (IMS) III chronicled the saga of endovascular therapy trialed against medical treatment for acute ischemic stroke. These recent randomized studies, however, largely neglect current device technology available for endovascular therapy as advanced by the TREVO2 and SOLITAIRE™^TM FR With the Intention For Thrombectomy (SWIFT) studies. Such exhaustive efforts in recent trials have failed to introduce a new treatment for stroke that unequivocally improves patient outcomes. Collateral perfusion is widely recognized to vary across individuals in any population and exerts a dramatic effect on baseline variables including the time course of ischemic injury, stroke severity, imaging findings, and therapeutic opportunities. Similarly, collaterals have been recognized to influence recanalization, reperfusion, hemorrhagic transformation, and subsequent neurological outcomes after stroke. Collateral lessons may be gleaned from these trials, to expand consideration of overall study results and perhaps most importantly, alter ongoing and new trials in development. Detailed analyses of available information on collaterals from these trials demonstrate that collaterals may be more influential than the choice of treatment modality or intervention.

Keywords:

• Stroke
• Ischemia
• Collateral
• Neuroprotection
• Reperfusion

Acknowledgements

This work has been supported by National Institutes of Health –National Institute of Neurological Disorders and Stroke awards (NIH/NINDS) P50NS044378, K24NS072272, R01NS077706, R13NS082049.