Literature

Curbside Consults Podcast


Published November 26, 2019

Intravenous thrombolysis has been an essential component in the management of acute ischemic stroke. Current guidelines recommend that thrombolysis be administered within 3 hours of the onset of first neurologic symptoms. However, two recent trials published in NEJM challenge this time paradigm. In this episode of Curbside Consults, Dr. Steven Feske, Director of the Stroke Division at Brigham and Women’s Hospital and Associate Professor of Neurology at Harvard Medical School, takes a deeper dive into the evolution of acute stroke treatment since the original thrombolysis trials and discusses the results of the recent WAKE-UP and EXTEND trials. 

Introduction - 00:00
Introduction of expert: Dr. Steven Feske - 01:33
Definition and underlying causes of acute ischemic stroke - 01:48
What is thrombolysis? - 02:54
How does tPA work? - 03:28
NINDS rt-PA Stroke Study and FDA approval of a 3-hour window - 03:50
Where the 4.5-hour thrombolysis limit came from - 06:00 (ECASS I, ECASS II, ATLANTIS & ECASS III)
What proportion of patients meet the thrombolysis time cutoff? - 08:10
Advances in stroke management since the NINDS rt-PA trial and what we have learned about pathophysiology - 09:18
Basics of mechanical thrombectomy - 12:20
Shortcomings of “last seen well” timing - 13:26
WAKE-UP Trial - 15:12
EXTEND Trial - 18:00
Differences between WAKE-UP and EXTEND - 20:16
Validity of trial results given early termination of both trials - 23:20
How will these trials change practice? - 24:25
Take-home messages - 25:50

Additional Resources:

1. Tissue Plasminogen Activator for Acute Ischemic Stroke (NINDS rt-PA Stroke Study)
2. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS trial)
3. Thrombolysis with Alteplase 3 to 4.5 hours after Acute Ischemic Stroke (ECASS III trial)
4. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset (WAKE-UP trial)
5. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke (EXTEND trial)

The Curbside Consults series complements the foundational information in Rotation Prep by taking a deep dive into key clinical topics with expert clinicians and educators. These podcasts explore and critique the evidence behind clinical practice and break down statistical concepts for the busy clinical trainee.

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Steven Feske, MD is Director of the Stroke Division at Brigham and Women’s Hospital and Associate Professor of Neurology at Harvard Medical School.
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Angela Chen was a 2018-2019 NEJM editorial fellow. She is an endocrine fellow who trained at Flinders Medical Centre and the Royal Adelaide Hospital. Angela recieved her medical degree from the University of Adelaide, and masters of public health from the University of Sydney. Her clinical and research interests are in the areas of glucocorticoid and cardiovascular endocrinology and diabetes medicine.
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