As a medical community, we are clearly focused on trying to
do something to help those with acute ischemic stroke. There is no doubt that
this is a common and devastating disease but an effective up ED treatment to
benefit the majority of patients has met with failure.
This is not for lack of trying.
Thrombolysis clearly has mixed reviews and is only indicated
in a very small percentage of patients. Prior interventional trials published
in 2013 were negative. But times change and perhaps technology improves. So
along comes Mr Clean.
This was an RCT performed in 16 centres in the Netherlands
comparing interventional treatment to “usual care.” But to be clear from the
beginning, usual care meant tPA the vast majority of times. Patients were
enrolled within 6 hours of onset of symptoms and had to have a proximal clot
demonstrated by formal imaging.
90% of all the patients got tPA at a median time of about 90
minutes from stroke onset before they were randomized in to the study. In fact,
the median time to randomization was 200 minutes. Therefore this study really
was looking at interventional therapy as a rescue option after tPA. Do you
think they would have proceeded with interventional therapy if the patient was
demonstrating significant early improvement in the ED? Of course not. This was a sicker and highly selected group of patients that did quite poorly in the end.
The primary outcome measure was looking at the odds ratio in
an ordinal shift analysis of the modified Rankin score at 90 days. You got
that? This type of analysis has been all the rage in the stroke literature
recently as it provides some statistical efficiency to find differences. The
only challenge is most clinicians have no idea how to interpret this result.
How do we translate this outcome measure in to a meaningful one that we can use
when engaging in informed decision making? But to be fair, they did report
simpler secondary outcome measures.
The results? It seemed to work as in this highly selected
patient population in these motivated study centres. The odds ratio for the primary
outcome was 1.67 (95% CI 1.21 to 2.30). Who really knows what that means? There was an absolute difference of 13.5% in
the rate of functional independence (mRs 0 to 2) in favour of the intervention
32.6% vs. 19.1%. So, a number needed to treat of about 7.
What should we take home from this? Interventional therapy
might work in a few highly selected patients with proximal clots that fail
thrombolysis. Of course the patient must present to an experienced centre that
provides this high level of service. One might be tempted to extrapolate these
results to other patient populations. But caution should certainly be in order
as prior studies of less selected patients have not met with positive results. Beware
indication creep.
In the end, this really will not help many patients. On
average, this study enrolled about 10 patients per year per centre (500
patients over 3 years in 16 centres). Should we be focusing huge amounts of
time, effort and money to benefit so few patients? Should we be focusing
efforts elsewhere? Who knows?
Covering:
Berkhemer OA, Fransen PSS, Beumer D, et al. A Randomized
Trial of Intraarterial Treatment for Acute Ischemic Stroke. N Engl J Med
2015;372:11-20.
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