Lytics in Stroke Study Reanalysis
Salim Rezaie, MD and Anand Swaminathan, MD
- The use of thrombolytic drugs in the management of acute ischemic stroke continues to be
- Some recent articles reanalyze the results of NINDS and ECASS III.
- There are 13 randomized controlled trials that look at the use of thrombolytics.
- Eleven trials are negative. They did not show benefit for thrombolysis.
- Two studies showed a benefit for alteplase
- NINDS (1995): NNT = 8-9 for benefit within 3 hours of stroke onset. NNH (ICH) = 16
- ECASS III (1998): NNT = 20 for benefit within 3 - 4.5 hours of stroke onset. NNH = 11
- The NINDS Trial had some limitations.
- Fragility index = 3 (ie, if the outcomes of 3 patients were changed from benefit to no benefit, the study would lose statistical significance).
- A re-analysis by Jerry Hoffman (2009) controlled for a number of factors including stroke severity (in NINDS, the placebo group had more severe strokes) and pre-existing disability.
- It found no benefit to thrombolytic therapy and an increased rate of ICH in groups randomized to thrombolytics.
- ECASS III Reanalysis (Alper 2020)
- Fragility Index = 1 in original ECASS III
- The re-analysis controlled for baseline imbalances in stroke severity between groups that may have biased the ECASS III results.
- It found no benefit to thrombolytics in ischemic stroke presenting between 3 - 4.5 hours and an increased rate of ICH in groups randomized to thrombolytics.
PERSPECTIVES
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- Bottom Line: there are no trials supporting the use of thrombolytics in the 3 - 4.5 hour acute ischemic stroke window.
Related content:
EM:RAP 2021 June Rick’s Rants: Thrombolytics in Stroke
PCMA Archive - December 2009 A Graphic Reanalysis Of The Ninds Trial
EMA 2020 September 2020 Abstract 10: Thrombolysis 3-4.5 hours after stroke: trial reanalysis
https://ebm.bmj.com/content/25/5/168
Adan A. - October 11, 2021 8:11 PM
Great review, simple and to the point. Thank you Salim & Swami.
There is just one thing I would like to know...
What does Salim say to his patients when he is discussing the option for tPA. I mean, what are the words patients hear, including numbers.
I have my own verbiage that so far, seems to work. But I am sure I can improve it with some words from the master.
Thanks guys ✌🏼
Ian L. - October 14, 2021 6:06 PM
The Cochrane 2014 mega analysis concluded that IV Thrombolytics if given within 3 hours of stroke onset derived benefit at 90 days but there was doubly increased mortality at 48 hours due mainly to intracranial bleeding .
This is devastating for a patient family and treating doctor .
Crushes the psyche .
But there are studies that show that 2/3 Dose reduces the intracranial bleeding by half and the results at 90 days are “non- inferior “. A .patient ought have the knowledge and the option .
This plus the option of Mechanical Thrombectomy for Large Vessel occlusion .
Byron F. - November 1, 2021 4:32 AM
neurologists at our hospital use "30% of patients who receive this medication do better compared to no treatment". This is lying with statistics, since it is a relative rather than an absolute difference.