These times they are a-changing – goodbye time window for reperfusion?

Author: Giuseppe Reale, MD, Catholic University of the Sacred Heart, Department of Neurosciences, Institute of Neurology. University Hospital “Fondazione Policlinico A. Gemelli”- Rome, Italy.

The American Heart Association/American Stroke Association recently published new Guidelines for the management of acute ischemic stroke (link here)1.

Undoubtedly one of the most striking news is the extension of the “therapeutic window” for mechanical thrombectomy, namely the removal of the blood clot that is causing the stroke, up to 24 hours after the onset of symptoms.

Compared to the “classic” 4.5 hours for intravenous thrombolysis and the 6 hours for mechanical thrombectomy, the new Guidelines shed a revolutionary light on the stroke treatment paradigm. Indeed, two recent large trials (DEFUSE 3 and DAWN)2,3 have evaluated the efficacy of mechanical thrombectomy respectively within 16 hours and 24 hours after stroke onset. Both trials were addressed to those patients, otherwise out of time for thrombolysis or thrombectomy, whose clinical and radiological features suggested the presence of still savable brain tissue. In particular, the DEFUSE 3 trial considered the difference between the volumes of the “dead” and the “dying” brain areas (the “mismatch”), while the DAWN trial took in account the “mismatch” between the stroke clinical severity and the volume of the lesion.

Although the aforementioned new indications widen the possibilities of intervention in acute ischemic stroke, there is a risk that increased time window for thrombectomy may mislead patients and their relatives to think they do not have to urgently contact emergency services.

In fact, it must be specified that the aforementioned mechanical thrombectomy inclusion criteria are very strict; in general, patients must have an occlusion of a large vessel (internal carotid artery or the initial tract of the middle cerebral artery), a relatively small brain lesion at baseline CT or MRI and severe clinical deficits. In addition, only mechanical thrombectomy within 16 hours is strongly recommended (two trials confirm the efficacy), while mechanical thrombectomy within 24 hours has a less strong level of evidence (one trial confirms the efficacy). Moreover, the actual Guidelines state that DEFUSE 3 and DAWN eligibility should be strictly adhered to in clinical practice. Thus, as recently discussed for thrombectomy within 6 hours4, the strict adherence to trials eligibility criteria will probably limit the access to mechanical thrombectomy between 6 and 24 hours to a relatively small number of patients in the near future. It is reasonable to hypothesize that new trials will broaden the eligibility criteria for 6-24 hours treatment, as happened before for intravenous thrombolysis.

Put all this together, it is clear that, at the moment, having 24 hours after stroke onset does not mean having more time. Thus, the sentence “time is brain” and the FAST (Face, Arm weakness, Speech disturbances and Time) acronym remain the most important educational message to spread by implementing public education programs, as strongly recommended by the new Guidelines too. Reducing the delay in stroke symptoms recognition and emergency system activation is crucial in order to widen the number of patient eligible for reperfusion therapies. When that is said, we have to remember that stroke clinicians’ work actually begins much earlier, being crucial to remember our role in stroke primary prevention and patient education too.




  1. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018 Jan 24
  2. Albers GW, Marks MP, Kemp S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. NEJM. 2018 Jan 24
  3. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. 2018;378:11-21
  4. El Tawil S, Cheripelli B, Huang X, et al. How many stroke patients might be eligible for mechanical thrombectomy? ESJ. 2016;1:264–271