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Opinion

EDITORIAL

Endovascular Thrombectomy for Ischemic Stroke


The Second Quantum Leap in Stroke Systems of Care?
Steven Warach, MD, PhD; S. Claiborne Johnston, MD, PhD

In 2015, the publication of 5 clinical trials1-5 established the ef- the intersection of the 5 trials: patients who are free from dis-
ficacy of endovascular thrombectomy for reducing disability ability prior to the stroke, have occlusion of the internal ca-
from large artery ischemic stroke, with each trial demonstrat- rotid artery or proximal middle cerebral artery, received treat-
ing the same superiority of ment with tPA within 4.5 hours from of onset according to
thrombectomy compared guidelines from professional medical societies, have clinical
Related article page 1279
with standard care. Endovas- severity of 6 or greater on the National Institutes of Health
cular stroke therapymost recently with the use of stent re- Stroke Scale, have a small infarct core defined as a score of 6
trievers to rapidly recanalize the artery during stent deploy- or greater on Alberta Stroke Program Early Computed Tomog-
ment and complete the thrombectomy by withdrawing the raphy score (ASPECTS), and can have the procedure (arterial
stent that had engaged the clot during stent deployment puncture) initiated less than 6 hours from symptom onset. The
had been practiced prior to that time, despite uncertainty about guidelines also include recommendations about the need to
its uses and benefits. After nearly 2 decades since intrave- optimize systems of care to increase access and reduce times
nous tissue plasminogen activator (IV tPA) became the first to treatment, without a specific prescription for how to do so.
proven therapy for ischemic stroke, the findings from these Will the evidence supporting effective thrombectomy
trials indicated that major changes in stroke management and transform the way stroke is assessed and managed beyond the
stroke systems of care were about to occur. application of the thrombectomy procedure, just as occurred
The US Food and Drug Administration approval of IV tPA in with tPA 20 years ago? The profound effect of early time to
1996 has arguably benefitted a greater percentage of patients with treatment suggests that systems must change substantially to
stroke than the small minority of patients with ischemic stroke achieve the maximum benefit for the most patients.
who have received the drug.6 The concept of stroke as a treat- The Highly Effective Reperfusion Evaluated in Multiple En-
able emergency was a major shift in clinical practice. Following dovascular Stroke Trials (HERMES) collaboration9 pooled indi-
tPA approval, in-hospital stroke code teams were formed, primary vidual patient data from the 5 positive trials to investigate effi-
and comprehensive stroke centers were developed and prolif- cacy in subgroups too small to be conclusive in the individual
erated, and vascular neurology emerged as a discrete specialty. trials. The study results showed no heterogeneity of the treat-
Although stroke centers were developed to maximize the ment effect across prespecified subgroups and a number needed
number of patients treated with tPA and minimize delays to to treat with thrombectomy of 2.6 patients to achieve a reduc-
initiation of tPA treatment, these centers had the broader ben- tion in disability of at least 1 level on the modified Rankin score.9
efit of holding hospitals to evidence-based standards for in- In this issue of JAMA, the report by Saver and colleagues10
patient management across the spectrum of cerebrovascular further defines the relationships of treatment times to benefit
diseases. Out-of-hospital emergency medical systems (EMSs) from the HERMES collaboration, and quantifies the inverse re-
developed stroke protocols and guidelines to transport pa- lationship of workflow delays with treatment benefit. With re-
tients to the stroke centers where they were most likely to re- spect to the organization of stroke services, understanding of
ceive tPA with the shortest delays. Public education cam- timing is among the most important factors in improving out-
paigns for the recognition of stroke signs and urgency of calling comes. The authors pooled data from 1287 patients enrolled in
911 are now more common on billboards and public service an- the 5 thrombectomy trials,1-5 including 634 assigned to receive
nouncements. Telestroke programs were developed to direct endovascular thrombectomy plus medical therapy and 653 as-
stroke thrombolysis decisions at hospitals without the in- signed to receive medical therapy alone. The time from symp-
house expertise. Large stroke registries created to track tPA sta- tom onset to randomization was approximately 3 hours (196
tistics and performance metrics, have yielded a wealth of in- minutes). Among patients who received endovascular throm-
sights about stroke risk factors, demographics, prevention, and bectomy, the time from symptom onset to arterial puncture was
outcomes unrelated to tPA7. nearly 4 hours (238 minutes), and time from symptom onset to
The effects of thrombectomy in reducing disability and re- reperfusion was nearly 5 hours (286 minutes).
storing functional independence were remarkably robust and The authors found that the degree of benefit, measured as
consistent across 5 independent trials, notwithstanding trial the degree of disability (modified Rankin Scale score) at 3
differences in time-to-treatment windows and imaging selec- months, was greater at earlier time to initiation of treatment and
tion criteria.1-5 The practice guideline8 that was derived based at earlier time to achieving substantial reperfusion. Overall ef-
on these studies recommends thrombectomy for patients at ficacy significantly declined for every hour delay from symp-

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Opinion Editorial

tom onset to arterial puncture and for every hour delay from The biggest opportunities to improve outcomes through
symptom onset to the achievement of substantial reperfusion. time reductions may involve the EMS system, but these op-
However, the benefit of thrombectomy extended to as long as portunities also pose the biggest challenges. In the HERMES
7 hours and 18 minutes from symptom onset to the time of pro- collaborative data, symptom onsetto-reperfusion time was de-
cedure initiation. Expansion of the time window would make layed 2 hours for patients transferred between facilities com-
the benefit of this treatment accessible to more patients, albeit pared with those transported directly to the treating facility,10
at the tail of the efficacy curve. These data have important im- suggesting a potential benefit for an additional 12.8% of treated
plications for how stroke services should be organized, includ- patients if the interhospital transfer was replaced by direct
ing the time at which thrombectomy should not be attempted. transport to the endovascular capable center. Another impor-
The potential benefit of earlier times to thrombectomy that tant consideration is among all patients with acute stroke symp-
could be achieved by reducing workflow delays will require toms, only a small fraction, estimated at less than 5%, may be
substantial system changes. Organizations that certify stroke candidates for endovascular thrombectomy therapy.12
centers may attempt to help improve outcomes by requiring Throughout the country EMS directors and personnel are
endovascular-capable stroke centers to meet aggressive goals, debating the best protocols to triage patients directly to endo-
such as 60 minutes from hospital arrival to arterial puncture vascular capable facilities: Which out-of-hospital stroke scale
and 90 minutes from hospital arrival to achievement of sub- to use for identifying large artery occlusions? Would telemedi-
stantial reperfusion.11 cine directed by a remote stroke physician be a better triage tech-
To enable more patients with ischemic stroke to have ac- nique? Should primary stroke centers be bypassed to transport
cess to endovascular thrombectomy, interfacility transfers to patients to comprehensive centers, even if it means delaying the
endovascular-capable stroke centers must increase, and trans- start of IV tPA? How much delay in bypass is acceptable? How
fers must be accomplished with the utmost of speed. If the re- much of a delay to start IV tPA would eliminate the benefit of
ferring facilities are linked to receiving facilities by video tele- earlier thrombectomy? Would a mobile stroke unit with CT an-
communication and routinely include vascular imaging giography and out-of-hospital tPA administration be the best
(CT angiography) for assessing eligibility for thrombectomy by way to triage to comprehensive stroke centers for thrombec-
the receiving team, redundant assessments and delays may be tomy? There is no consensus and there has been no organiza-
eliminated at the receiving hospital (where the patients could tion with the authority to choose, promulgate, and enforce stan-
be transported directly to the angiography suite), potentially dardized EMS transport protocols on a national scale, despite
saving an estimated 30 to 45 minutes based on the workflow much discussion and debate about these issues. These ques-
times observed by Saver and colleagues. The authors also es- tions are testable, and clinical trials comparing EMS strategies
timated from the magnitude of the outcomes observed in the for stroke triage and treatment are feasible.13
HERMES analysis that for every 1000 patients achieving sub- The next major clinical trials in acute stroke therapeutics may
stantial endovascular reperfusion, 15 minutes faster emer- be the testing of out-of-hospital strategies to improve outcomes
gency department doorto-reperfusion time would result in with thrombectomy by substantially reducing times to reperfu-
39 patients having a less-disabled outcome at 3 months, in- sion (eg, NCT02795962). In the meantime, communities in the
cluding 25 who would achieve functional independence. An United States and in other developed countries will be evaluat-
hour faster to reperfusion was estimated to benefit an addi- ing new triage approaches, as previously occurred in the success-
tional 15.6% of patients successfully treated. ful evolution of care for trauma and acute coronary syndrome.

ARTICLE INFORMATION perfusion-imaging selection. N Engl J Med. 2015; ischemic stroke regarding endovascular treatment.
Author Affiliations: Dell Medical School, University 372(11):1009-1018. Stroke. 2015;46(10):3020-3035.
of Texas at Austin, Austin. 4. Saver JL, Goyal M, Bonafe A, et al. 9. Goyal M, Menon BK, van Zwam WH, et al.
Corresponding Author: S. Claiborne Johnston, MD, Stent-retriever thrombectomy after intravenous Endovascular thrombectomy after large-vessel
PhD, Dell Medical School, University of Texas at t-PA vs t-PA alone in stroke. N Engl J Med. 2015;372 ischaemic stroke. Lancet. 2016;387(10029):1723-1731.
Austin, 110 Inner Campus Dr, Austin, TX 78705 (clay (24):2285-2295. 10. Saver JL, Goyal M, van der Lugt A, et al. Time to
.johnston@austin.utexas.edu). 5. Jovin TG, Chamorro A, Cobo E, et al. treatment with endovascular thrombectomy and
Conflict of Interest Disclosures: The authors have Thrombectomy within 8 hours after symptom outcomes from ischemic stroke: a meta-analysis.
completed and submitted the ICMJE Form for onset in ischemic stroke. N Engl J Med. 2015;372 JAMA. doi:10.1001/jama.2016.13647
Disclosure of Potential Conflicts of Interest and (24):2296-2306. 11. McTaggart RA, Ansari SA, Goyal M, et al. Initial
none were reported. 6. Jauch EC, Saver JL, Adams HP Jr, et al. hospital management of patients with emergent
Guidelines for the early management of patients large vessel occlusion (ELVO). J Neurointerv Surg.
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