So what does this all mean?
My suspicion that tPA isn’t all it’s cracked up to be is fleshed out in the previous 4 and a half parts.
If I bored the teeth off you let me try a snappy conclusion
The evidence for tPA for stroke is problematic because
1) significant heterogeneity in the trials in terms of:
- CT definitions and exclusions
- variations in severity of stroke
2) significant base line variations (favouring tPA) in the populations of the two +ve trials
3) a predominance of negative findings overall (2 postive trials and 9 negative trials)
4) every single trial is either funded directly by the manufacturers or the authors have significant conflicts of interest with writers and researchers working directly for the company. NINDS may be an exception to this as the drug was supplied by genentech but overall finding was via the NIH. The article doesn’t provide detailed conflict information
Where I work mostly, the stroke team deal with any potential lytic cases. For once I’m very glad that EM in Ireland is dysfunctional enough that we’re not taking the lead on this.
For example – i’m not entirely sure how to approach informed consent on this. How do you explain the complexities of this to a patient?
Having said that…
My suspicion is that thrombolysis is beneficical for certain people with certain strokes, I’m not convinced we know who those patients are yet.
I find the overwhelming support for such a controversial and potentially dangerous (approved on the basis of a 300 patient trial despite multiple negative trials) treatment to be premature.
I think the way forward from here is to replicate the findings of the NINDS trial with a substantial population (as was done repeatedly with lytics for STEMI) in a non-pharma sponsored trial.
I used to say that there wasn’t the slightest appetite for this to be done.
But it’s nice to be wrong.
It’ll have finished enrolling by the time this blog post is published.
Here’s a quick run-down of the trial
- 0-6 hrs with stroke
- no blood on imaging (i don’t see any mention of the subtle stroke signs in their protocol)
- randomised to tPA or placebo
- primary outcome is mRS 0-2 (remember in most trials it’s been 0-1) assessed by postal questionnaire or telephone interview at 6 months. It’s a bit disappointing that it’s follow-up by phone/post as that could cause problems if there’s a high lost to follow-up rate
- non-pharma funded and minimal conflicts in the authors (it’s very hard to have none!)
This is gonna be a 3000 patient trial. To put that in context, the cochrane systematic review of lytics in stroke has 2955 patients in it.
If any trial is gonna give us the answer then this one will.
So I look forward to having my mind changed! No doubt you’ll hear more from me when it gets published.