NEWS & VIEWS

STROKE treatment of patients beyond 3months, but

no meaningful differences were apparent

Long-term outcome of endovascular between the groups with regard to carotid

endarterectomy, use of anticoagulant or anti

therapy for ischaemic stroke platelet agents, antihypertensive treatment, or

hospitalization for any cause within the first
3months. Consequently, the observation of
Charlotte Zerna and Mayank Goyal early beneficial effects that persisted for 1year
strongly suggests that the improved outcome
In patients with acute ischaemic stroke resulting from anterior circulation was due to treatment withtPA6.
occlusion, endovascular therapy provides greater long-term benefits Information regarding vital status at
thandoes intravenous tissue plasminogen activator. However, further 2years poststroke was available for 459 of 500
patients enrolled in the MRCLEAN trial. The
improvement of systems of care and research regarding adjunct therapies cumulative 2year mortality was 26.0% in the
isstill needed. endovascular treatment group and 31.0% in
the control group (adjusted HR0.9, 95%CI
Refers to van den Berg,L.A. etal. Two-year outcome after endovascular treatment for acute ischemic stroke. N.Engl.
J.Med. 376,13411349 (2017) | Davalos,A. etal. Safety and efficacy of thrombectomy in acute ischaemic stroke 0.61.2, P=0.46)3. The increase in mortality
(REVASCAT): 1year followup of a randomised open-label trial. Lancet Neurol. 16, 369376 (2017) in both groups compared with the 90day fol
lowup data observed in the MRCLEAN trial
Advances in stroke imaging, availability of 1.80 (95%CI 1.022.99)4. These results are is part of the natural history of the disease, as
new thrombectomy devices, and emphasis by not surprising in view of the fact that acute many patients with severe disability (mRS=5)
neurovascular care teams on speed of work ischaemic stroke is an episodic event and not a have limited life expectancy, probably owing
flow have paved the way for success of six chronic illness. If one adequately treats the ini to multiple factors, including pneumonia,
randomized controlled trials of endovascular tial stroke event and subsequently controls the other infections, and deep vein thrombosis
treatment for acute ischaemic stroke (FIG.1). In underlying risk factors that originally led to the with pulmonary embolism.
October 2014, the MRCLEAN investigators occurrence of the stroke, then the initial effect The long-term followup results of the
were the first to report superiority of endo size of interventional treatment compared with MRCLEAN and REVASCAT trials show a
vascular treatment for acute ischaemic stroke conservative treatment will be preserved. similar degree of superiority of endovascular
caused by anterior circulation occlusion1. This This concept of preserved effect was pre therapy over control therapy to the 90day
result led to early termination of enrolment viously demonstrated in the initial trial of results. The REVASCAT investigators found
for four other trials of endovascular therapy: tissue plasminogen activator (tPA) versus that 89% of the treatment effect at 1year
ESCAPE, EXTENDIA, SWIFT-PRIME, and standard medical therapy for acute ischaemic was already observed at 90days, and 80%
REVASCAT. A meta-analysis of these trials, all stroke that was published in 1995 (REF.5). In of the treatment effect at 1year was already
of which used modified Rankin Scale (mRS) this trial, the primary outcome (mRS score) observed at 5days4. If the effect of an acute
score at 90days as their primary outcome, measured at 3months favoured treatment therapy (either tPA or endovascular ther
showed that patients who received endo with tPA; similarly, the long-term 6month apy) on the initial poststroke deficit is main
vascular treatment had significantly reduced and 12month data continued to show out tained,it is only logical to conclude that early
disability compared with those who received comes in favour of the tPA arm6. The study outcome predicts the results of long-term
standard medical treatment (OR2.49, 95%CI group did not collect data on subsequent outcomemeasures. This association is also a
1.763.53; P<0.0001)2. Now, the MRCLEAN
and REVASCAT investigators have published
long-term followup results at 2years and a b c d
1year, respectively 3,4.
In total, 391 of 500 patients enrolled in
MRCLEAN (78.2%) had 2year followup
data and were included in the analysis, which
resulted in an adjusted OR of 1.68 (95%CI
1.152.45) for distribution of mRS scores,
in favour of endovascular treatment over
conventional treatment 3. The REVASCAT
investigators also found a persistent benefit of Figure 1 | Endovascular treatment in acute ischaemic stroke. a|CT angiography showing left middle
endovascular therapy: analysis of mRS scores cerebral artery occlusion. b|First conventional angiography run confirmingNature Reviews
left middle | Neurology
cerebral artery
at 1year, which were available for 205 of 206 occlusion. c|Retrieved thrombus with the stent retriever device that was used. d|Final conventional
patients (99%), resulted in an adjusted OR of angiography run showing restored flow to the left middle cerebral artery territory.

NATURE REVIEWS | NEUROLOGY www.nature.com/nrneurol

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NEWS & VIEWS

These trials have had a
major effect on stroke treatment,
but further improvement is
required
reflection of the success of strategies aimed at
secondary prevention of acute stroke. Similarly
to REVASCAT, the ESCAPE investigators
found that early post-baseline markers of
stroke severity (NIH Stroke Scale trajectory)
in the first 48h poststroke could accurately
predict outcomes among individuals treated
with endovascular therapy 7.
These trials have had a major effect on
stroke treatment, but further improvement is
required. Implementation science has come
a long way since the evidence-based move
ment took root to promote higher-quality,
patient-focused care, but patients still receive
substandard, variable care that is all too fre
quently inappropriate and unsafe8. A number
of patients with large vessel occlusions are
probably missing out on treatment because
of a lack of timely access to the appropriate
hospital, rapid brain death, and/or technical
challenges to achieving rapid reperfusion.
Although endovascular therapy increases ini
tial treatment costs, this approach is projected
to improve quality-adjusted life expectancy
and reduce health-care costs over a lifetime
horizon compared with tPA9. Reorganization
of regional transport systems should be pri
oritized in order to expand access to endovas
cular therapy and organize systems of care to
shorten doortoreperfusion times, as well as
to centralize treatment to high-volume com
prehensive stroke centres with coverage 24h a
day, 7days a week10. Improved technology and
training of frontline staff are needed to better
triage patients who are likely to be suitable
candidates for endovascular treatment.
The success of endovascular therapy
has created an effective human ischaemia
reperfusion model. Testing of new treatments
in the prehospital arena or at primary stroke
centres will facilitate knowledge translation
from animal work into patients, and could
result in promising adjunct therapies that
prevent infarct growth. One such therapy,
the neuroprotectant NA1, is already being
tested in patients with major acute ischaemic
strokein the ESCAPENA1 trial.
Charlotte Zerna and Mayank Goyal are at the Seaman
Family Magnetic Resonance Research Centre,
FoothillsMedical Centre, 1403 29th Street NW,
Calgary, Alberta T2N 2T9, Canada.
Correspondence to M.G.
mgoyal@ucalgary.ca
doi:10.1038/nrneurol.2017.78
Published online 2 Jun 2017
1. Berkhemer,O.A., van Zwam,W.H. & Dippel,D.W.
Stent-retriever thrombectomy for stroke. N.Engl.
J.Med. 373, 1076 (2015).
2. Goyal,M. etal. Endovascular thrombectomy after
large-vessel ischaemic stroke: a meta-analysis of
individual patient data from five randomised trials.
Lancet 387, 17231731 (2016).
3. van den Berg,L.A. etal. Two-year outcome after
endovascular treatment for acute ischemic stroke.
N.Engl. J.Med. 376, 13411349 (2017).
4. Davalos,A. etal. Safety and efficacy of thrombectomy
in acute ischaemic stroke (REVASCAT): 1year
followup of a randomised open-label trial.
LancetNeurol. 16, 369376 (2017).
5. The National Institute of Neurological Disorders and
Stroke rtPA Stroke Study Group. Tissue plasminogen
activator for acute ischemic stroke. N.Engl. J.Med.
333, 15811587 (1995).
6. Kwiatkowski,T.G. etal. Effects of tissue plasminogen
activator for acute ischemic stroke at one year.
N.Engl. J.Med. 340, 17811787 (1999).
7. Sajobi,T.T. etal. Early Trajectory of stroke severity
predicts long-term functional outcomes in ischemic
stroke subjects: results from the ESCAPE trial
(Endovascular Treatment for Small Core and Anterior
Circulation Proximal Occlusion With Emphasis on
Minimizing CT to Recanalization Times). Stroke 48,
105110 (2017).
8. Rapport,F. etal. The struggle of translating science
into action: foundational concepts of implementation
science. J.Eval. Clin. Pract. http:dx.doi.org/10.1111/
jep.12741 (2017).
9. Shireman,T.I. etal. Cost-effectiveness of solitaire
stent retriever thrombectomy for acute ischemic
stroke: results from the SWIFT-PRIME trial (Solitaire
With the Intention for Thrombectomy as Primary
Endovascular Treatment for Acute Ischemic Stroke).
Stroke 48, 379387 (2017).
10. Holodinsky,J.K. etal. Drip and ship versus direct to
comprehensive stroke center: conditional probability
modeling. Stroke 48, 233238 (2017).
Competing interests statement
M.G. declares grant support from Covidien, consulting fees
from Medtronic and Stryker, and grant support from GE
Healthcare. C.Z. declares no competing interests.

NATURE REVIEWS | NEUROLOGY www.nature.com/nrneurol

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