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tPA… That’ll Kill You

December 5, 2016

Short Attention Span Summary

Nothing like a little tPA!
People get fired up over tPA in stroke.  Some are believers.  Some are vehemently not.  The Australian authors present an excellent meta-analysis that comes to the conclusion that thrombolysis improves functional outcome in acute ischemic stroke but comes at the cost of increased intracranial hemorrhage and early mortality.  Thanks to Dr. Kendall Bein for making me aware of this article!

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I agree with the authors’ conclusion.  “The available data are unlikely to resolve the controversy…”  I am not opposed to tPA, but I think the patient and family deserve true informed consent.


Emerg Med Australas. 2016 Oct;28(5):496-510. doi: 10.1111/1742-6723.12653. Epub 2016 Aug 25.

Review article: Why is there still a debate regarding the safety and efficacy of intravenous thrombolysis in the management of presumed acute ischaemic stroke? A systematic review and meta-analysis.

Donaldson L1, Fitzgerald E2,3, Flower O2,4, Delaney A2,4,5.

Author information:

1Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia. lachlandonaldson@gmail.com.

2Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia.

3Faculty of Health, University of Technology Sydney, Sydney, New South Wales, Australia.

4Northern Clinical School, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.

5ANZIC Research Centre, Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Victoria, Australia.



The objective of the present study is to independently and systematically assess the harms and benefits of intravenous thrombolysis for patients with presumed acute schaemic stroke.


We performed a systematic review and meta-analysis of randomised clinical trials of intravenous thrombolysis compared with control in patients with presumed acute ischaemic stroke. The effectiveness of thrombolysis on functional outcome, symptomatic intracranial haemorrhage, early mortality and mortality at final follow up was assessed using a fixed-effect meta-analysis.


A total of 26 studies that randomised 10 431 participants were included. The use of thrombolysis was associated with an increased odds of good functional outcome, estimated odds ratio (OR) 1.14 (95% confidence interval [CI] 1.04-1.25, P = 0.004), and also a significantly increased risk of symptomatic intracranial haemorrhage, estimated OR 4.28 (95% CI 3.34-5.48, P < 0.0005) and an increased risk of early mortality, estimated OR 1.51 (95% CI 1.27-1.78, P < 0.0005). There was no statistically significant evidence that the effect of recombinant tissue plasminogen activator (rt-PA) was different from that of other thrombolytic agents. There was also an increase in mortality at final follow up associated with treatment with thrombolysis, estimated OR 1.17 (95% CI 1.06-1.30, P = 0.003), although this result was not consistent when limited to studies of rt-PA, estimated OR 1.04 (95% CI 0.92-1.18, P = 0.49).


There is clear evidence of increased early mortality, increased rates of symptomatic intracranial haemorrhage and also of improved functional outcomes for patients with presumed acute ischaemic stroke treated with thrombolysis. The available data are unlikely to resolve the controversy regarding the use of intravenous thrombolysis in this population, and further randomised controlled trials are urgently required.

© 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

PMID: 27561375 [PubMed – in process]

What are your thoughts?