Current Acute Stroke Trials and the Therapeutic Time Window

Abstract and Introduction

Abstract

Several trials in acute stroke are underway or have been completed recently. Among the latter, ECASS 3 was a milestone regarding the extension of the rigid 3-h time window out to 4.5 h for intravenous thrombolysis with recombinant tissue plasminogen activator. Several other approaches are being tested for thrombolytic therapy, among them modern imaging-based patient selection of patients and interventional approaches. Other pharmaceutical strategies include neuroprotection, and restoration, biophysical approaches, such as near infrared laser therapy, hemodynamic augmentation, and sphenopalatine ganglion stimulation. This perspective will cover the recently completed and currently recruiting acute stroke trials with respect to their potential role in expanding the therapeutic time window for acute ischemic stroke.

Introduction

Stroke is among the top three ranking global burdens of disease, the third-leading cause of death and a leading cause of permanent disability worldwide. At present, the only approved therapy for acute ischemic stroke is intravenous tissue plasminogen activator (tPA), provided it is administered within 3 h, although a change of the European label is pending following the results of the ECASS 3 trial with an extension of the time window out to 4.5 h.^[1] This narrow time frame for therapeutic action has impeded effective treatment for the majority of ischemic stroke patients. Further extending the time window for acute stroke therapies is an important endeavor for increasing the number of stroke patients who might benefit from treatment.^[2] Several and varying strategies have been employed to treat ischemic stroke in later time windows – most of these have failed to date and none have at present been proven safe and efficacious, with the exception of decompressive hemicraniectomy in patients with malignant middle cerebral artery (MCA) stroke younger than 60 years of age.^[3] Some of these old and new strategies are still under investigation, whether aiming at clot removal, improving cerebral hemodynamics, or utilizing a presumably neuroprotective and neuroreparatory approach. This perspective aims to update and extend our previous work on the topic. We review these strategies with regard to their potential for extending acute stroke therapy beyond the 3–4.5 h time window.

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