|MR CLEAN||ESCAPE||EXTEND-IA||SWIFT PRIME||REVASCAT|
|Age Range||≥ 18||≥ 18||≥ 18||18 - 80||18 - 85|
|NIHSS Range||≥ 2||> 5||None stated||8 - 29||≥ 6|
|Time Window||6 hours||12 hours||6 hours||6 hours||8 hours|
|IV tPA Treatment||89%||76%||100%||100%||73%|
|Vascular Lesions||Distal ICA, M1, M2, A1, or A2||Carotid T, Carotid L, M1, or all M2s||ICA, M1, or M2||Intracranial ICA, carotid terminus, or M1||ICA or M1|
|Penumbral Assessment||None||ASPECTS ≥6|
on Multiphase CTA
|CT or MR perfusion mismatch|
(see paper for definition)
|Hypodensity or DWI |
< 1/3 of MCA territory
ASPECTS ≥ 6
|ASPECTS ≥ 7|
|Primary Outcome(s)||Shift in mRS at 90 days||Shift in mRS at 90 days||Reduction in perfusion lesion volume|
NIHSS reduction ≥ 8 points
or to score of 0-1 at day 3
|Distribution of mRS at 90 days|
% mRS 0-2 at 90 days
|Shift in mRS at 90 days|
|Primary Result(s)||Odds ratio 1.67||Odds ratio 2.6||100% vs. 37% reperfusion|
80% vs. 37% NIHSS
|Cochran-Mantel-Haenszel p-value = 0.0002||Odds ratio 1.7|
|mRS 0-2 at 90 days||33% vs. 19%||53% vs. 29%||71% vs. 40%||60% vs. 36%|
|44% vs. 28%|
|sICH Risk||7.7% vs. 6.4%||3.6% vs. 2.7%||5.7% vs. 5.7%|
|1% vs. 3.1%|
|4.9% vs. 1.9%|
|Mortality||18.9% vs. 18.4%||10.4% vs. 19.0%||8.6% vs. 20%|
|Absolute values not reported|
3.7% absolute difference in favor
|18.4% vs. 15.5%
Lots of exciting news coming from Nashville, as expected. In addition to MR CLEAN, we now have positive results from ESCAPE, EXTEND-IA, and SWIFT PRIME. I thought it might be useful to line up the key clinical and radiographic inclusion criteria and outcomes in a table. I’m new to table-making, so I’ll try to adjust the column widths if I get time later; I think the basic idea comes through. Update: Here’s a link to a full-screen picture of the table.
A few observations: First, all three of the published papers (the SWIFT PRIME study isn’t published yet–the link above is to the slides from the oral abstract session) included links to their protocols and supplementary data sets. Kudos!
Next, I thought it interesting that MR CLEAN included subjects with NIHSS down to 2. Looking through the paper and the supplementary information, I found subgroup analyses at the higher NIHSS ranges, but nothing about the very low range (e.g., how many subjects actually had NIHSS of 2, or 2-5? Was endovascular treatment beneficial for them?) This is important because from time to time we do see patients with seemingly minor strokes and large vessel occlusions. We’re then faced with the difficult decision whether to offer them revascularization right away, or wait to see if they deteriorate. Note that struggling with this second order question is quite a luxury, born of the fact that the basic principles of endovascular treatment are quickly becoming established.
I think the most heterogenous (and therefore interesting) aspect of these studies is their assessment of tissue viability (penumbra). As far as I can tell, MR CLEAN didn’t require such. However, the manuscript does state that they employed the uncertainty principle, meaning that the local investigators enrolled subjects if they felt uncertain as to whether endovascular treatment would benefit them. Presumably, these investigators would have excluded potential subjects who had low ASPECT scores, or who had perfusion imaging suggesting large infarct cores. Employing the uncertainty principle is not ideal, as it assumes that investigators know who clearly will and who clearly won’t benefit from treatment, which is, in fact, the very question under study. My guess is that having some wiggle room regarding subject selection was necessary in order to get everyone on board with the randomized trial.
ESCAPE employed two means of penumbral assessment: ASPECTS and multiphase CT perfusion. The former assesses whether the parenchyma is irreversibly damaged using CT hypodensity. The latter is relatively new to the literature and assesses the degree of collateral blood flow by visual inspection of the CTA at several time points.
EXTEND-IA required CT- or MR perfusion imaging, using prolonged mean transit time to identify the ischemic tissue and reduced cerebral blood volume to identify the irreversibly damaged tissue.
SWIFT PRIME started out by excluding potential subjects with large areas of hypodensity on CT or high signal intensity on DWI. Later on, they added a requirement that the ASPECT score be at least 6.
So, on the one hand the studies used varying methods to exclude subjects unlikely to benefit from revascularization. On the other hand, all of the studies were positive, so perhaps the specific method doesn’t matter so long as those with predicted large infarct cores are excluded. If it is true that there are several ways to ascertain the extent of salvagable vs. non-salvagable brain, then perhaps the simplest one should prevail. Assigning an ASPECT score and assessing collateral flow with multiphase CT are pretty straightforward (this website has training materials), whereas post-processing of CT perfusion data takes some time, and MRI is always inconvenient.
Anyway, it’s been a great week for stroke research and will be very interesting to see how systems of care develop in response to these results. Here’s a link to the International Stroke Conference’s “Late-Breaking Science” web page, which in turn has links to many other interesting studies presented this year.
Update 2/13/15: Table edited to reflect ESCAPE’s inclusion of subjects with NIHSS > 5.
Update 5/14/15: Table updated with REVASCAT data.