SGEM Xtra: Are tPA Stroke Trials Really Fragile?

Date: August 18th, 2022 Reference: Munn et al. Fragility Index Meta-Analysis of Randomized Controlled Trials Shows Highly Robust Evidential Strength for Benefit of <3 Hour Intravenous Alteplase. Stroke 2022 Dr. Jeff Saver Guest: Dr. Jeff Saver is a Professor and SA Vice Chair for Clinical Research, Carol and James Collins Chair, Department of Neurology, Director of the UCLA Comprehensive Stroke and Vascular Neurology Program at the David Geffen School of Medicine at UCLA. This is an SGEM Xtra. Jeff and I have an interesting back story to how we met. I knew about Jeff from his multiple publications in the stroke literature. I did not know he knew about me until an EM physician sent me a video of a presentation that was given at an international stroke meeting. On one of the slides, Professor Daniel Fantovich and I were referred to as "Non-Expert EM Contrarians". I reached out to Jeff and we had a very good conversation. He clarified what he meant by “non-experts”: that we were not stroke neurologists or emergency physicians with subspecialty neuro expertise, such as having completed fellowship training in neurologic critical care. He did acknowledge that both Dr. Fatovich and I had expertise on critical appraisal of the medical literature. The conversation ended well with Jeff requesting one of the t-shirts I planned to make with the title of non-expert ER contrarian on the chest. Jeff recently reached out to me with his new publication called Fragility Index Meta-Analysis of Randomized Controlled Trials Shows Highly Robust Evidential Strength for Benefit of <3 Hour Intravenous Alteplase asking about my thoughts.  I thought this would be a great opportunity to dig deeper into the fragility index and have another expert in stroke neurology on the SGEM. Dr. Eddy Lang We have had a couple of individuals previously on the SGEM who strongly support the use of tPA in acute ischemic stroke (AIS). One was Dr. Eddy Lang who is a well-known Canadian researcher and emergency physician in Calgary, Alberta. Eddy appeared on the SGEM Xtra episode called the Walk of Life discussing AIS.  We had a debate on the issue of tPA for stroke published in CJEM 2020 as part of their debate series. Eddy is also the senior author on the CJEM article summarizing the Canadian Stroke Best Practice (CSBP) 2018 Guidelines. This Canadian guideline gives a level “A” recommendation for the use of tPA in AIS in patients last seen normal within 4.5 hours. “All eligible patients with disabling ischemic stroke should be offered intravenous alteplase (tPA). Eligible patients are those who can receive intravenous alteplase (tPA) within 4.5 hours” of symptom onset time or last seen normal (Evidence Level A; Section 5.3.i). We also had a neurology resident on to critically appraise a systematic review and meta-analysis of endovascular therapy plus/minus tPA as a bridging therapy (SGEM#349). A few more publications have come out since that podcast and the European Stroke Organization (ESO) recommends intravenous thrombolysis before mechanical thrombectomy in patients with acute ischemic stroke and anterior circulation large vessel occlusion. There have been several tPA skeptics on the SGEM including Dr. Hoffman, Dr. Fatovich, and Dr. Morgenstern. However, not until now have we had a stroke neurologist who is very much in support of using tPA in AIS. I think it is very important to try and mitigate against echo chambers, our own biases and listen carefully to other points views. Fragility Index Meta-Analysis of Randomized Controlled Trials Shows Highly Robust Evidential Strength for Benefit of <3 Hour Intravenous Alteplase. Jeff was asked a number of questions about his new publication. Some of the answers are listed as bullet points, but most of his responses can be heard in full by listening to the SGEM podcast: Who were your co-authors on this publication? Why did you decide to write this article?