Posted by: Chris Cole | April 5, 2013

Fibrinolysis and delayed angioplasty not as flash as the PR blurb would have you believe

Published in the NEJM last month was a study titled “Fibrinolysis or Primary PCI in ST-Elevation Myocardial Infarction”… or “the STREAM trial” to its friends. This is a largish (n = 939 + 943) and fairly well-designed randomised interventional trial comparing two treatment strategies for all-comers with STEMI who presented within 3 hours of symptom onset but could not get to primary PCI within one hour. The treatment arm was given tPA (tenecteplase) as soon as possible and then had delayed (6-24 hrs) PCI. The control arm got no tPA but got to primary PCI as soon as possible. The primary outcome was a composite of death, shock, CCF, or re-infarction at/within 30 days.

Interestingly, 36% of the tPA group required urgent rescue angioplasty due to failure of reperfusion with fibrinolysis (median time to PCI = 2.2 hrs). The patients who were given tPA and did reperfuse had a median time to PCI = 17 hrs. The primary PCI group had a median time to PCI = 178 mins, or close enough to 3 hrs.

They found no significant difference in primary outcome between the two groups. Rates of intracerebral haemorrhage were 1.0% vs 0.2% for the tPA and primary PCI groups respectively, and the need for CABG was 4.7% vs 2.1% for tPA vs PCI as well. Both differences were statistically significant given the power of the study.

This trial was funded by Boehringer Ingelheim, the manufacturer of tenecteplase, and while maintaining quite rigorous objectivity, the authors summary conclusion was that:

“…a strategic alignment of prehospital or early fibrinolysis and contemporary antithrombotic cotherapy coupled with timely coronary angiography resulted in effective reperfusion in patients with STEMI who presented within 3 hours after symptom onset and who could not undergo PCI within 1 hour after the first medical contact. However, early fibrinolysis was associated with a slightly increased risk of intracranial bleeding”.


Not an entirely unreasonable precis of the results, but I think I would probably portray the findings a little differently in light of the spectre of the “discussions” with my cardiologically inclined colleagues that will undoubtedly ensue when decisions have to be made about urgent transfer for PCI for a 3am STEMI patient versus early tPA at a smaller centre and delayed PCI.

A couple of points are worth noting before everyone jumps on the “tPAyyy and de-layyy” bandwagon (complete with satisfied smiles and holding of hands):

– There was no difference in primary (cardiac) outcome for the punters in each group.

– 36% of the tPA/delay group required urgent rescue PCI to achieve this equality.

– The tPA/delay group had a 5-fold increased risk of ICH.

– The tPA/delay group had a 2-fold increased requirement for CABG.

For me, the practical upshot of all of this is:

My remote STEMI patient has a 74% chance of the optimal outcome (minimum cardiac badness at 30 days), 5 times the risk of ICH, and twice the risk of needing a CABG if I choose to give then tPA and transfer them in a leisurely manner for PCI, rather than having them haul arse to the cath. lab. as soon as possible.

I am but a simple emergency doctor, a wandering vagrant, an illegal alien, if you will, in the ivory, monitored-bed-lined  tower of academic cardiology. But given the information above, call me demanding, but I’m going to be advocating transfer for primary PCI every time.

Interestingly, the median time to urgent primary PCI in this trial was 178 minutes, suggesting that the current consensus international guidelines for choosing early tPA over transport for PCI if the delay to PCI is > 90 minutes might be a little too conservative; the subjects in the urgent PCI arm of this trial had equivalent cardiac outcomes and a lesser adverse event rate (ICH, need for CABG) with a median PCI delay of 3 hours. The tricky question is still what to do with the STEMI patient who is 1-2 hours from your cath. lab… do you give them tPA pre-hospital (or pre-transfer from a smaller centre) aiming for a chance (significantly < 100%) at earlier reperfusion at the expense of a higher risk of bleeding, or transfer them urgently without thrombolysis, as this study suggests that we can expect equivalent benefit from just scooping and running to the cath. lab at least out to 3 hours.

In summary, one can still debate the merits of tPA vs no tPA if you can get to PCI in under 2-3 hours, but in light of the STREAM trial results, I think it is reasonably clear that even if you do opt for tPA, there is no evidential basis for intentionally delaying transfer for PCI as soon as possible.

The full text of the paper can be found here:



  1. […] (who manufacture and sell tenecteplase) sponsored the STREAM trial, which I have previously discussed in detail here. Recapping the greatest […]

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