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Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke

June 2018
American Journal of Neuroradiology 39(6):E61-E76

June 2018
39(6):E61-E76

DOI:10.3174/ajnr.A5638

Authors:

Jeffrey S Carpenter

West Virginia University

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. mTICI Revascularization Scale Scores (30,31,113)

…

. mRS Scores (35)

…

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Standards of Practice

Multisociety Consensus Quality

Improvement Revised Consensus

Statement for Endovascular Therapy

of Acute Ischemic Stroke

From the American Association of Neurological Surgeons

(AANS), American Society of Neuroradiology (ASNR),

Cardiovascular and Interventional Radiology Society of Europe

(CIRSE), Canadian Interventional Radiology Association (CIRA),

Congress of Neurological Surgeons (CNS), European Society of

Minimally Invasive Neurological Therapy (ESMINT), European

Society of Neuroradiology (ESNR), European Stroke Organization

(ESO), Society for Cardiovascular Angiography and Interventions

(SCAI), Society of Interventional Radiology (SIR), Society of

NeuroInterventional Surgery (SNIS), and World Stroke

Organization (WSO)

David Sacks MD, Blaise Baxter MD, Bruce C.V. Campbell MBBS, PhD,

Jeffrey S. Carpenter MD, Christophe Cognard MD PhD,

Diederik Dippel MD PhD, Muneer Eesa MD, Urs Fischer MD,

Klaus Hausegger MD, Joshua A. Hirsch MD,

Muhammad Shazam Hussain MD, Olav Jansen MD,

Mahesh V. Jayaraman MD, Alexander A. Khalessi MD MS,

Bryan W. Kluck DO, Sean Lavine MD, Philip M. Meyers MD,

Stephen Ramee MD, Daniel A. Ru

¨fenacht MD,

Clemens M. Schirmer MD PhD and Dierk Vorwerk MD,

From the Department of Interventional Radiology (D.S.), The Reading

Hospital and Medical Center, 6th and Spruce Sts., West Reading, PA

19612; Department of Radiology (B.B.), Erlanger Medical Center,

Chattanooga, Tennessee; Departments of Medicine and Neurology

(B.C.V.C.), Melbourne Brain Centre at the Royal Melbourne Hospital,

University of Melbourne, Parkville, Victoria, Australia; Department of

Radiology (J.S.C.), West Virginia University, Morgantown, West Virginia;

Department of Diagnostic and Therapeutic Neuroradiology (C.C.),

Centre Hospitalier Universitaire de Toulouse, Ho

ˆpital Purpan,

Toulouse, France; Department of Neurology (D.D.), Erasmus University

Medical Center, Rotterdam, The Netherlands; Department of Radiology

(M.E.), University of Calgary, Calgary, Alberta, Canada; Department of

Neurology (U.F.), Inselspital–Universita

¨tsspital Bern, Bern, Switzerland;

Department of Radiology (K.H.), Klagenfurt State Hospital, Klagenfurt

am Wo

¨rthersee, Austria; Neuroendovascular Program, Department of

Radiology (J.A.H.), Massachusetts General Hospital, Boston,

Massachusetts; Cerebrovascular Center, Neurological Institute (M.S.H.),

Cleveland Clinic, Cleveland, Ohio; Department of Radiology and

Neuroradiology (O.J.), Klinik fu¨r Radiologie und Neuroradiologie, Kiel,

Germany; Departments of Diagnostic Imaging, Neurology, and

Neurosurgery (M.V.J.), Warren Alpert School of Medicine at Brown

University, Rhode Island Hospital, Providence, Rhode Island;

Department of Surgery (A.A.K.)

University of California San Diego Health, San Diego, California;

Interventional Cardiology (B.W.K.), Heart Care Group, Allentown,

Pennsylvania; Departments of Neurological Surgery and Radiology

(S.L.), Columbia University Medical Center/New York–Presbyterian

Hospital, New York, New York; Departments of Radiology and

Neurological Surgery (P.M.M.), Columbia University College of

Physicians & Surgeons, New York, New York; Interventional

Cardiology, Heart & Vascular Institute (S.R.), Ochsner Medical Center,

New Orleans, Louisiana; Neuroradiology Division (D.A.R.), Swiss Neuro

Institute–Clinic Hirslanden, Zu¨ rich, Switzerland; Department of

Neurosurgery and Neuroscience Center (C.M.S.), Geisinger Health

System, Wilkes-Barre, Pennsylvania; and Diagnostic and Interventional

Radiology Institutes (D.V.), Klinikum Ingolstadt, Ingolstadt, Germany

This article was previously published in the Journal of Vascular and

Interventional Radiology. The articles are identical except for minor stylistic

and spelling differences in keeping with each journal’s style. The JVIR article

should be usedwhen citing this article ina journal. ßSociety of Interventional

Radiology, 2018 J Vasc Interv Radiol 2018; 29:441–453. https://doi.org/10.

1016/j.jvir.2017.11.026. Permissions: www.elsevier.com/permissions

Corresponding author:

David Sacks, Department of Interventional Radiology, The Reading

Hospital and Medical Center, 6th and Spruce Sts., West Reading, PA

19612.

Email: david.sacks@towerhealth.org

International Journal of Stroke, 0(0)

International Journal of Stroke

0(0) 1–21

DOI: 10.1177/1747493018778713

journals.sagepub.com/home/wso

Abbreviations

ASPECTS: Alberta Stroke Program Early Computed Tomography Score; EVT: endovascular therapy; mRS: modified

Rankin scale; mTICI: modified thrombolysis in cerebral infarction; NIHSS: National Institutes of Health Stroke Scale;

QI: quality improvement; SAH: subarachnoid hemorrhage; SICH: symptomatic intracranial hemorrhage; SITS-MOST: Safe

Implementation of Thrombolysis in Stroke Monitoring Study; TICI: thrombolysis in cerebral infarction: TIMI: thromb-

olysis in myocardial infarction; TPA: tissue plasminogen activator.

Received: 17 November 2017; accepted: 23 November 2017

Introduction

Endovascular therapy (EVT) for acute ischemic stroke

in selected patients has recently been proven eﬀective in

several clinical trials, and the widespread adoption of

thrombectomy into routine clinical practice has begun.

However, these acute stroke services are resource-inten-

sive, including advanced cerebral imaging and highly

trained multidisciplinary hospital teams rapidly

responding to emergency activation. Despite the previ-

ous acceptance of intravenous ﬁbrinolysis for acute

ischemic stroke and the development of designated

stroke centers (1), ischemic stroke remains a leading

cause of adult death and disability (2). Many patients

are not candidates for ﬁbrinolysis, and intravenous

therapy is relatively ineﬀective for severe strokes as a

result of large cerebral artery occlusions. Moreover, it is

uncertain if the beneﬁts of endovascular stroke treat-

ment in the trial setting can be generalized to clinical

care provided by hospitals and teams of varying train-

ing, experience, and case volume. In other medical dis-

ciplines, rapid technologic advancement required

guidelines to utilize these tools eﬀectively and respon-

sibly (3). Quality-improvement (QI) metrics for the out-

comes of endovascular ischemic stroke treatment were

published by a multisociety, multispecialty, inter-

national consensus group in 2013 (4). These QI metrics

have been accepted at a national level in Great Britain

and Ireland (5) but have yet to be included into stroke

center accreditation requirements in the United States.

Subsequent to the publication of the prior QI guide-

lines, 8 randomized trials and several meta-analyses of

EVT have been published (6–20). These randomized

trials have established EVT as standard of care when

available (5,21–23), and provide additional data on

which to update the metrics and benchmarks of the

previous paper (4). Therefore, it is now appropriate to

revise the prior QI document based on new evidence.

Revision of this QI consensus statement remains

focused on processes of care and patient outcomes.

Other documents address standards for physician train-

ing (24,25) and recommendations for patient selection

and treatment methods (5,23). As in the previous guide-

lines, it is intended that these benchmarks be used in a

quality-improvement program to assess and improve

processes and outcomes in acute stroke revasculariza-

tion. The benchmarks provide the consensus process

and outcome consensus measures called for by the

Stroke Treatment Academic Industry Roundtable

(STAIR) IX academic industry roundtable for the

next generation of endovascular trials (26). The bench-

marks may also be suitable for accreditation of stroke

intervention programs. Most of the metrics apply to the

role of the interventional physician, regardless of spe-

cialty or particular board certiﬁcation, but comprehen-

sive stroke care requires a broad multidisciplinary

process involving care that ranges from emergency dis-

patch of paramedics through acute hospital care and

posttreatment subacute rehabilitation. Therefore,

although it is not the intention of this document to

assess in detail the quality of facilities, some of the met-

rics also apply to institutional policies and procedures

for stroke care.

Materials and methods

A literature search was conducted using Ovid and

EMBASE from 2012 (from the last date of the litera-

ture search for the ﬁrst publication of these metrics) (4)

to October 2015 using article titles that included the

following: (acute ischemic stroke OR cerebrovascular

accident OR stroke) AND (intra-arterial OR intraarter-

ial OR endovascular OR angioplasty OR stent OR

stent retriever OR mechanical thrombectomy OR

thrombolysis OR tissue plasminogen activator [TPA]

OR TPA OR urokinase OR streptokinase OR alteplase

OR tenecteplase). Additional articles were then soli-

cited from writing group members. An evidence table

(Table E1, available online at www.jvir.org) was con-

structed by using articles that were randomized con-

trolled trials, registries, or case series of at least 100

patients, and some case series of less than 100 patients

were included if the series provided uniquely useful

data. From the evidence table, metrics were chosen

that were believed to be important markers of quality

of care. Thresholds for metrics were then chosen by

consensus of the writing group based on review of the

evidence table. Consensus was deﬁned as 80% of the

writing group. If consensus was not achieved during

International Journal of Stroke, 0(0)

2International Journal of Stroke 0(0)

discussion, a modiﬁed Delphi process was used to

obtain consensus (27). If consensus was not achieved

after the modiﬁed Delphi process, a threshold was not

chosen. The evidence table was then updated by using

the same search terms in February 2017 at the time of

completion of the draft of the document to allow

updating of the metrics if appropriate.

Standards for developing clinical practice guidelines

were reviewed (28). It was determined that the majority

of these standards were not applicable for this docu-

ment that updates quality benchmarks for processes

and outcomes of care rather than creating recommen-

dations for types of patient care. For this reason, this

revision has been changed to a consensus statement

rather than a guideline.

Definitions

Measures and metrics will depend on the deﬁnition of a

good outcome or a complication and the time at which

patients are assessed for these outcomes, as many

patients show gradual improvement following an ische-

mic stroke. Numerous trials have used varying deﬁn-

itions for similar concepts. The deﬁnitions used in this

document were derived from review of these trials and

then consensus of the writing group.

Ischemic central nervous system infarction.—A

uniformly accepted simple deﬁnition of central nervous

system infarction remains elusive. A successful multi-

disciplinary attempt arrived at a deﬁnition as

follows (29):

Central nervous system infarction is deﬁned as brain,

spinal cord, or retinal cell death due to ischemia,

based on:

1. Pathological, imaging, or other objective evidence of

cerebral, spinal cord, or retinal focal ischemic injury

in a deﬁned vascular distribution; or

2. Clinical evidence of cerebral, spinal cord, or retinal

focal ischemic injury based on symptoms persisting

at least 24 hours or until death, and other etiologies

excluded.

Door-to-event time.—The term ‘‘door’’ is used to

determine the time of onset of medical care, as in

‘‘door to time of computed tomography (CT) ima-

ging.’’ It is deﬁned as the time of arrival in the emer-

gency department for an outpatient or the time ﬁrst

discovered to have a stroke for an inpatient. When

patients are transferred, ‘‘door’’ refers to the arrival

(ie, registration) time at the receiving facility.

Time to thrombus.—Time to thrombus is considered

to represent the start of endovascular lytic infusion or

ﬁrst placement of a mechanical device in the target

vessel.

Successful revascularization.—Successful revascular-

ization is considered to represent modiﬁed thromboly-

sis in cerebral infarction (mTICI) (30,31) grade 2b or 3

ﬂow through the previously occluded vessel segment

(Table 1).

Symptomatic intracranial hemorrhage.—

Symptomatic intracranial hemorrhage (SICH) is a par-

enchymal hematoma type II (per the Safe

Implementation of Thrombolysis in Stroke

Monitoring Study [SITS-MOST] deﬁnition) (32) or

subarachnoid hemorrhage (SAH) with neurologic

deterioration leading to an increase in National

Institutes of Health Stroke Scale (NIHSS) score >4

or leading to death within 36 hours of treatment.

Because of the risk of vessel perforation during endo-

vascular procedures, SAH has been added as a cause of

intracranial hemorrhage to the SITS-MOST SICH def-

inition (33).

This deﬁnition is similar to that used in the recent

randomized trials of EVT (7,11,15). Several of the

authors of those trials have joined others in proposing

Table 1. mTICI Revascularization Scale Scores (30,31,113)

Score Description

0 No perfusion, complete obstruction; no flow past occlusion of ‘‘major’’ vessel

1 Perfusion past initial obstruction but limited distal branch filling with little/slow distal perfusion

2a Partial perfusion: <50% of ‘‘major’’ vascular territory perfused (eg, filling and complete perfusion through one

M2 division)

2b Partial perfusion: 50% of major vascular territory is filled, but there is not complete and normal perfusion of

entire territory

3 Complete or full perfusion with filling of all distal branches

mTICI: modified thrombolysis in cerebral infarction.

International Journal of Stroke, 0(0)

Sacks et al. 3

a new deﬁnition of SICH (34). These new deﬁnitions

have not yet been validated on a larger scale, adopted in

stroke trials, or applied to the outcomes of the recent

randomized trials. Therefore, the original deﬁnition of

SICH is maintained in the present revision of the con-

sensus statement and modiﬁed to include any intracra-

nial hemorrhage associated with a decrease in NIHSS

score >4 or death within 24 hours of the end of the

revascularization procedure (20).

Good clinical outcome.—A good clinical outcome is a

measure of neurologic functional with a score of 0–2 on

the modiﬁed Rankin scale (mRS; Table 2) (35) assessed

90 days after treatment. This does not exclude clinically

signiﬁcant beneﬁt in patients in whom an mRS score of

2 is not achieved.

Indications and Contraindications

EVT for acute ischemic stroke with large vessel occlu-

sion is established in guidelines as the standard of care

(22,36). If the patient is also eligible for intravenous

TPA, this drug should be administered as a ‘‘bridging’’

strategy in parallel without delaying thrombectomy.

Waiting to assess ‘‘response’’ to TPA is strongly dis-

couraged (22), as clinical improvement may not indi-

cate recanalization. The rate of TPA-induced

recanalization before thrombectomy (performed with-

out delay) was <10% in recent randomized trials

(11,13,20). Proceeding directly to thrombectomy (ie,

direct thrombectomy) should be performed in appro-

priate candidates with a contraindication to TPA,

including risk of hemorrhage or when >4.5 hours

have elapsed since stroke onset.

Indications and contraindications for EVT are based

on subgroup analyses of randomized trials and case

series. Clinical trials tend to have more restrictive cri-

teria, whereas case series represent more of a ‘‘real-

world’’ experience. Potential selection criteria are

based on stroke severity, time (ie, duration of symp-

toms), imaging, clot location, age, and comorbidities.

Stroke severity.—Clinical trials have set variable

NIHSS score limits for eligibility, often requiring 6,

8, or 10 points. The Multicenter Randomized Clinical

Trial of Endovascular Treatment for Acute Ischemic

Stroke in the Netherlands (MR CLEAN) trial had a

minimum NIHSS score of 2 and Extending the Time

for Thrombolysis in Emergency Neurological Deﬁcits-

Intra-arterial (EXTEND-IA) had no NIHSS score

limits, but, given the requirement for large vessel occlu-

sion, few patients with NIHSS scores <6 were enrolled

(37). Individual patient data meta-analysis of ﬁve posi-

tive randomized trials (14) demonstrated highly consist-

ent treatment eﬀects across the NIHSS score spectrum,

at least for NIHSS scores 6. Data from observational

studies have demonstrated an important incidence of

large vessel occlusion in patients with clinically mild

stroke and a propensity for these patients to later

experience neurologic deterioration (38). The risk/bene-

ﬁt in patients with low NIHSS scores therefore needs to

be carefully considered, and future studies have to

address whether endovascular procedures are beneﬁcial

in patients with mild symptoms and proximal vessel

occlusion. There are no data supporting an upper

limit on stroke severity.

Time.—Most trials of intraarterial lytic agents and

mechanical revascularization devices have historically

required start of treatment within 6 or 8 hours (39–

42) for anterior-circulation strokes. The strongest evi-

dence for EVT is for treatment commenced within 6

hours (14,43). More rapid time to reperfusion has

been linked to improved clinical outcomes and is there-

fore an important consideration in patient selection

(43–45). A few patients in recent trials were treated at

6–8 hours in the Randomized Trial of

Revascularization with Solitaire FR Device versus

Best Medical Therapy in the Treatment of Acute

Table 2. mRS Scores (35)

Score Description

0 No symptoms

1 No significant disability: able to carry out all usual activities despite some symptoms

2 Slight disability: able to look after own affairs without assistance but unable to carry out all previous activities

3 Moderate disability: requires some help but able to walk unassisted

4 Moderately severe disability: unable to attend to own bodily needs without assistance and unable to walk unassisted

5 Severe disability: requires constant nursing care and attention, bedridden, incontinent

6 Dead

mRS: modified Rankin scale.

International Journal of Stroke, 0(0)

4International Journal of Stroke 0(0)

Stroke Due to Anterior Circulation Large Vessel

Occlusion Presenting within Eight Hours of Symptom

Onset (REVASCAT) trial (15) and at 6–12 hours in the

Endovascular Treatment for Small Core and Anterior

Circulation Proximal Occlusion with Emphasis on

Minimizing CT to Recanalization Times (ESCAPE)

trial (13). Individual patient data meta-analysis sug-

gests signiﬁcant beneﬁt to at least 7 hours, 18 minutes

(46). Observational studies have suggested that patients

presenting at later time points with favorable imaging

ﬁndings still beneﬁt from reperfusion (47), and this was

conﬁrmed in the DWI or CTP Assessment with Clinical

Mismatch in the Triage of Wake-Up and Late

Presenting Strokes Undergoing Neurointervention

with Trevo (DAWN) trial (48), which used clinical–

core mismatch criteria to select patients 6–24 hours

after the ‘‘last known well’’ time. In the DAWN trial

(48), independent functional outcome occurred in

48.6% of patients who underwent endovascular treat-

ment versus 13.1% of control patients (P<.0001) with

similar revascularization success as 0–6-hour thrombec-

tomy trials and no variation in treatment eﬀect between

the 6–12-hour and 12–24-hour treatment windows.

Other randomized trials in extended time windows are

ongoing (49,50). Vertebrobasilar occlusions have been

treated at extended times, sometimes more than 24–48

hours after symptom onset (51,52). This is partly

because of the traditional deﬁnition of onset as the

last known well time. Patients with basilar artery occlu-

sion may have prodromal mild symptoms in 60% of

cases before the development of severe deﬁcits (53).

The Basilar Artery International Cooperation Study

(BASICS) registry (53) advocated using time of severe

deﬁcit (ie, likely moment of occlusion) and found

that good outcome with reperfusion beyond 9 hours

of that time was extraordinarily rare (53).

Randomized trials in patients with basilar artery occlu-

sion are ongoing (54,55).

Imaging.—Noncontrast CT has been an essential

component of patient selection in randomized trials of

intravenous and endovascular revascularization for

treatment of acute stroke (1,7,11,13,15,20,39–41,56).

Absolute noncontrast CT contraindications to endo-

vascular treatment are similar to those for intravenous

thrombolytic agents and include the presence of acute

intracranial hemorrhage or a signiﬁcant established

infarct (1).

Infarct size can be approximated on noncontrast CT

by using the Alberta Stroke Program Early CT Score

(ASPECTS) (57,58). However, the score is not closely

related to infarct volume or functional eloquence and

has variable interrater agreement, particularly early

after stroke onset. In recent randomized trials, there

was clear beneﬁt in patients with ASPECTS 6–8 and

9/10. Relatively few patients with ASPECTS 0–5 were

included in the trials. The beneﬁt in this group

appeared to be of lesser magnitude, but a clinically

meaningful beneﬁt could not be excluded (14).

Patients with ASPECTS 3–5 will be evaluated in a ran-

domized trial (59).

The hyperdense middle cerebral artery sign can alert

clinicians to the presence of a large vessel occlusion.

This sign has a high degree of sensitivity if thin (1-

mm) slices are reconstructed and good speciﬁcity if

clearly asymmetric compared with the contralateral

artery (60). Clot length on noncontrast CT of more

than 8 mm has been associated with lower recanaliza-

tion rates after intravenous TPA (61), but this is not

absolute (62), and none of the positive randomized

trials considered clot length in determining eligibility.

The Randomized, Concurrent Controlled Trial to

Assess the Penumbra System’s Safety and

Eﬀectiveness in the Treatment of Acute Stroke

(THERAPY) trial that used this criterion was neutral

(18). There is evidence that occult anterograde ﬂow can

be associated with TPA-induced recanalization even in

the presence of a long thrombus (63).

The target vessel occlusion should be established by

using noninvasive angiography (CT or magnetic reson-

ance [MR] imaging), as practiced in all the positive

randomized trials. This also provides information on

proximal arterial pathology and catheter access. CT

angiography has also been used to grade the quality

of collateral ﬂow. However, there is potential for stand-

ard single early-phase acquisitions to underestimate

late-arriving collateral ﬂow and therefore exclude

patients who may beneﬁt. Dynamic angiography

derived from CT perfusion or multiphase CT angiog-

raphy acquisitions avoids this pitfall (64).

Many centers use CT perfusion to improve diagnos-

tic sensitivity and provide an estimate of tissue viability,

which is closely related to the quality of collateral blood

ﬂow. A large volume of ischemic core (eg, >70 mL) on

CT perfusion is certainly associated with a worse prog-

nosis, but whether this alters treatment eﬀect within 6

hours of stroke onset is yet to be clariﬁed. Some case

series have suggested a beneﬁt of reperfusion even in

patients with a large ischemic core >100 mL (65).

Analysis of the MR CLEAN trial did not reveal treat-

ment eﬀect heterogeneity between cases of <70 and

>70 mL core, although the absolute probability of

independent functional outcome in those with a core

>70 mL was only 8% (66). Rather than excluding

patients from treatment as a result of a large ischemic

core, the presence of favorable imaging may be useful

in deciding to pursue treatment in patients with other-

wise less favorable clinical characteristics. Estimation

of ischemic core volume by using CT perfusion com-

bined with age and NIHSS score in clinical–core mis-

match was shown to identify patients who beneﬁt from

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Sacks et al. 5

thrombectomy in the extended time window of 6–24

hours in the DAWN trial (48).

MR imaging with diﬀusion imaging, with or without

perfusion imaging, is increasingly used in some centers.

There are some logistic challenges of safety screening

and rapid access to MR scanners that have to be over-

come to avoid relevant delays in treatment. However, in

the high-performing centers in the Solitaire With

the Intention For Thrombectomy as PRIMary

Endovascular treatment (SWIFT PRIME trial) (44),

there was no signiﬁcant diﬀerence in arrival to random-

ization time according to image modality (ie, CT vs

MR imaging), suggesting that MR-related delay is not

inevitable. Uncertainties regarding whether core

volume is truly treatment eﬀect–modifying or simply

prognostic apply, as discussed with CT perfusion (65).

It is also important to note that measured perfusion

lesion volumes vary between processing software pro-

grams and the thresholds used to estimate ischemic core

may vary with time (67).

Clot location.—The randomized trials demon-

strated clear beneﬁt in internal carotid artery ter-

minus and M1 (ie, ﬁrst segment of middle cerebral

artery) occlusion, with or without tandem occlusion

in the cervical carotid artery (10,14). Arterial occlu-

sions arising more proximally are associated with

poorer outcomes. Most notably, ‘‘T-lesions’’ have

the poorest outcomes among anterior-circulation

strokes (68,69). Proximal M1 occlusions have worse

outcomes than distal M1 occlusions as a result of

occlusion of lenticulostriate arteries and basal ganglia

infarction, with an increased risk of reperfusion hem-

orrhage (70). More distal M2 occlusions were less

common among trial patients, and a clear beneﬁt

was not demonstrated, although there was no signiﬁ-

cant heterogeneity in treatment eﬀect observed. Many

patients with M2 occlusions were assessed as having

M1 occlusions at the site and reclassiﬁed as having

M2 occlusions by the core laboratory, leading to a

predominance of larger, more proximal occlusions.

Some case-control studies have suggested that beneﬁt

persists in M2 occlusions, with similar safety as M1

occlusions (71). Basilar artery occlusion was not

included in the recent trials, in some cases because

of perceived lack of equipoise and in others because

of concerns regarding excessive heterogeneity. The

BASICS trial (54) is ongoing, but many sites regard

the dismal prognosis if untreated and the clear

improvement associated with recanalization as suﬃ-

cient grounds to treat. EVT for occlusions in the

anterior cerebral artery, M3/4 segments, and poster-

ior cerebral artery has not been systematically stu-

died. More distal vessels are smaller and more

tortuous, which potentially increases procedural risk,

and the smaller territory at risk and increased eﬃcacy

of TPA reduces the beneﬁt. Further device develop-

ment may alter this balance in the future.

Age.—Although increased age is associated with a

worse prognosis after stroke in general, the recent

trials have clearly demonstrated a treatment eﬀect in

patients aged >80 years of at least the same magnitude

as in younger patients. Indeed, there is a signiﬁcant

mortality beneﬁt in elderly patients, with 20% absolute

risk reduction (number needed to treat ¼5) (10,14).

Importantly, the trials included only patients with inde-

pendent premorbid function, regardless of age, and the

potential quality-of-life beneﬁt for patients with signiﬁ-

cant comorbidities needs to be weighed in clinical prac-

tice. Prestroke dementia before endovascular

reperfusion has been linked with a low probability of

achieving a good clinical outcome (72). Some trials

have therefore excluded patients aged >80 years (73).

Older patients may also have tortuous arterial access,

which can complicate the procedure.

Medical comorbidities.—Most contraindications to

intravenous thrombolysis do not apply to EVT.

Overall, mechanical thrombectomy (with or without

intravenous TPA) has a similar risk of SICH compared

with TPA alone (10,14). There are relatively limited

data on the safety of EVT in patients with markedly

abnormal coagulation (eg, International Normalized

Ratio >3.0 or current use of novel or direct oral anti-

coagulant agents), and risks and beneﬁts need to be

considered on an individual basis.

The criteria chosen to select patients for treatment

will aﬀect outcomes. Patients at higher risk are more

likely to do poorly with or without treatment, but selec-

tion of only patients at low risk will deny clinical beneﬁt

to a large number of severely ill patients. Because pub-

lished selection criteria vary, there is no single ‘‘correct’’

list of inclusion and exclusion criteria. The American

Heart Association has published class I recommenda-

tions for EVT patient selection (22), but 40%–50% of

patients are now being treated outside of these class I

recommendations (74,75). Based on published data and

the desired ratio of beneﬁt to risk, each institution will

need to create and follow its own indications and

contraindications.

Metric 1: At least 90% of patients who meet the insti-

tutional selection criteria (ie, indications/contraindica-

tions) should be treated with endovascular therapy.

Process and outcomes metrics

In general, previously published endovascular stroke

therapy metrics (76) were designed to measure aggre-

gate performance of hospital or clinical outcomes. They

were neither designed nor intended to deﬁne individual

International Journal of Stroke, 0(0)

6International Journal of Stroke 0(0)

physician performance. In contrast, this document pro-

vides requirements for performance criteria for the indi-

vidual practitioner and the facility. The purpose of

these metrics is to deﬁne the minimum standards for

EVT in acute ischemic stroke patients. It is recognized

that a concerted team eﬀort is required to ensure eﬃ-

cient workﬂow, timely EVT, and safe, eﬀective care.

The recent endovascular trials have reiterated the

importance of appropriate patient selection and pro-

cedural performance such as timely and more complete

revascularization to improve the likelihood of achieving

a good clinical outcome. This paradigm is based on

selecting patients with potentially salvageable ischemic

penumbra. A noncontrast head CT/MR study and vas-

cular imaging such as CT/MR angiography will dem-

onstrate areas of established infarct and presence of a

proximal large vessel occlusion, respectively, and pro-

vide vital information to select patients for endovascu-

lar therapy.

Data collection

From a quality-assurance perspective, endovascular

therapy for acute ischemic stroke diﬀers slightly from

other areas in which quality initiatives, morbidity, and

mortality discussions focus on speciﬁc events in which

errors in care or complications occurred. The measure

of beneﬁt from endovascular stroke therapy is not

based on single or isolated cases, but rather is expressed

as a percentage of aggregated patients treated who can

function independently at 3 months. This has also been

measured by using shift analysis in the recent endovas-

cular trials (77). As demonstrated in those trials, clinical

beneﬁt from EVT is dependent on delivery of high-

quality care in a timely manner at the institutional

level by a dedicated team.

As such, performance metrics from large aggregates

of patients treated by endovascular means are com-

pared versus performance standards in clinical trials

in which beneﬁts were demonstrated, recognizing that

patients may be treated outside trial inclusion criteria

on a case-by-case basis. This requires all patients’ pro-

cedural, process, and clinical outcomes to be entered

into a database, trial, or registry (24,76,78–80).

Without the denominator of ‘‘all patients,’’ measures

of success and percentage descriptors are

meaningless. These data allow comparison of metrics

against benchmarks for individual operator perform-

ance, risk-adjusted clinical outcomes, and individual

and institutional process measures.

As stated in a prior document concerning

Comprehensive Stroke Centers (76), it is advantageous

to collect data in a standardized fashion to avoid redun-

dant eﬀorts. Data collection tools such as multicenter

registries will serve as useful benchmarks and will

facilitate an ongoing process of constant evaluation.

Multicenter registries are recommended over institu-

tional registries because of the ability to serve as a

benchmark against other institutions. There are numer-

ous examples of such data-collection tools for treat-

ment of acute ischemic stroke (78,80–82). A recent

publication looking at trends in endovascular therapy

and clinical outcomes within the Get With The

Guidelines–Stroke registry (83) demonstrates the utility

of strict data collection within well-maintained nation-

wide database systems.

Data collection for EVT is closely tied in with the

process already in place for patients who are eligible

for intravenous thrombolytic therapy and starts with

documentation of time of onset and the time the patient

arrives at the ‘‘door.’’ This could mean (i) the door of a

primary stroke center, where data collection should ide-

ally start, or, (ii) in cases being transferred to an endo-

vascular center, the time of registration at the center

that receives the patient. The detailed time metrics will

be discussed in the next section. Data collection, espe-

cially time points, should be as inclusive as possible,

with subsequent metrics being reported by combining

multiple elements. The mandatory threshold for collec-

tion of the minimum deﬁned elements is 100%.

Data concerning demographic characteristics are

used to identify various patient subgroups, whereas

other data points are pertinent for risk adjustment and

are necessary for evaluation of procedural and clinical

outcomes. These would include factors speciﬁc to the

individual case, such as location of occlusion and time

from onset, as well as demographic factors speciﬁc to

patient subgroups, such as age, race, and sex. Ancillary

data such as prognostic factors pertaining to comorbid-

ity, stroke severity, and imaging parameters may help in

risk- and severity-adjusted analysis to adjust for vari-

ability in case mix. Collection of these data points is

necessary for an appropriate evaluation of patient risk

factors and also for study of institutional factors that

could inﬂuence overall patient outcomes and have a

bearing on evaluation of operator performance.

At a minimum, these data should include age, sex,

premorbid mRS score, NIHSS score, location of occlu-

sion, various time points and intervals described in the

subsequent sections, blood pressure, blood glucose level

at presentation, and presence of atrial ﬁbrillation.

Speciﬁc data-collection metrics for EVT have already

been included in national guidelines (22,23,36). Other

data elements may be helpful and may become evident

with further research, such as radiation exposure and

contrast agent dose.

Metric 2: 100% of patients have the required minimum

process and outcomes data entered into an institutional

or national database, trial, or registry.

International Journal of Stroke, 0(0)

Sacks et al. 7

Time intervals

Emergency endovascular stroke treatment is one of the

most complex multidisciplinary functions a medical

institution chooses to undertake. Reperfusion treat-

ment (intravenous or endovascular) achieved within

the shortest period of time is widely accepted as a pre-

requisite for optimal clinical outcomes (45,84,85).

Subgroup analyses from several trials (43,86,87)

have shown that treatment delays resulted in signiﬁcant

decrease in the likelihood of a good outcome of endo-

vascular stroke therapy. Analysis of the pooled data of

5 endovascular trials (46) conﬁrmed this: every 1-hour

delay in time from onset to arterial puncture results in a

5.3% shift in the direction of more disability on

the mRS.

There are many steps from stroke onset to comple-

tion of treatment, and optimal and timely execution of

each of these steps is necessary to achieve the stated

goal. Numerous opportunities exist to minimize the

time needed for each step from the time of the acute

stroke to patient arrival to the hospital and then until

reperfusion is achieved.

Process improvement for emergency stroke treat-

ment should be an ongoing component of all stroke

systems of care and should focus on all the tasks and

activities in this complex sequence of events. These data

are then used for quality assessment/assurance and pro-

cess improvement and therefore directly relate to the

eventual clinical outcome of the patients being treated

by the team. To judge satisfaction of these performance

goals in regard to expeditious delivery of care, time

points and intervals are the units of measurement.

At a minimum, the time points and intervals speci-

ﬁed in this document should be tracked in all cases.

Institutions may choose to measure additional time

points. The more time points that are recorded, the

more exactly deﬁciencies might be identiﬁed; however,

this may prove onerous to document from a resource

perspective. For instance, delays in obtaining a CT scan

may result from delay in ordering the study, delay in

response by CT staﬀ (eg, multiple other procedures

being requested at the same time), or delay related to

transportation.

Acknowledgment of the critical importance of time to

reperfusion for obtaining favorable outcomes in myo-

cardial reperfusion treatments has led to the formation

of initiatives such as ‘‘Door to Balloon: An Alliance of

Quality’’ for patients with ST-segment elevation myo-

cardial infarction. The key was achievement of a door-

to-balloon time of <90 minutes for at least 75% of

patients presenting directly to the treating hospital by

using various strategies identiﬁed through research,

resulting in dramatic reductions in times (88,89).

The impressive results in shortening the time to myo-

cardial reperfusion for acute myocardial infarction

obtained by such initiatives provided an impetus for

launching similar initiatives related to intravenous

TPA for stroke (90). The Joint Commission has set a

more ambitious goal of 80% of patients treated within

1 hour for primary stroke centers (91). The experience

in reducing door-to-needle times reported by the group

from Helsinki (92) suggests that, with simple strategies,

median door-to-needle times of 30 minutes or even less

can be achieved. Because of the need for neurologic

assessment and imaging in addition to the emergency

medicine and interventional components, acute stroke

patients referred for EVT require more time for initi-

ation of treatment than patients with ST-segment ele-

vation myocardial infarction. Although rapid-response

mechanisms aiming to result in initiation of revascular-

ization therapies within the minimum amount of time

can be modeled according to the myocardial infarction

experience, it should be recognized that acute stroke

treatment, especially EVT, requires a far more complex

infrastructure. Notwithstanding that, it is clear that,

similar to the cardiology model, major improvements

in door-to-treatment time need to take place to increase

the proportion of favorable outcomes for patients trea-

ted with EVT for acute stroke (93).

Since the early years of endovascular stroke treat-

ment, various time metrics have been reported, with a

trend toward overall improvement in times. These were

initially reported on the basis of case series (94,95), with

newer metrics from registries (96,97), earlier device

trials (98,99), and recent randomized controlled trials

(10). These reports focused on median onset–to–groin

puncture times ranging from 200 minutes in the latest

randomized trials (10) to 277 minutes in registry data

(97). Recent trial data (10) have also reported various

components of these times, breaking them down into

intervals that include patient arrival times and imaging

times. In the ESCAPE trial (13), the authors reported a

median time from imaging to arterial puncture of 51

minutes and a median time from imaging to reperfusion

of 84 minutes. The median imaging-to-puncture time in

the SWIFT PRIME trial (20) was 57 minutes. The

Highly Eﬀective Reperfusion evaluated in Multiple

Endovascular Stroke trials (HERMES) meta-analysis

of treatment times from 5 recent large endovascular

trials (46) reported better clinical outcomes with faster

treatment times, with median door-to-imaging time of

19 minutes, imaging-to-puncture time of 76 minutes,

and puncture-to-reperfusion time of 44 minutes in the

entire cohort.

The endovascular trials represent optimal results

based on study site and patient selection. Many of the

endovascular trials included only study sites with a

proven ability to respond rapidly, excluded patients

with carotid dissections or internal carotid artery–

origin occlusions, and excluded patients who could

International Journal of Stroke, 0(0)

8International Journal of Stroke 0(0)

not be treated rapidly. However, the reported times in

recent trials did include time taken for patient random-

ization. These rapid responses have not been uniformly

achieved in other trials, registries, or case series

(18,100–102). Nevertheless, the time intervals in this

consensus statement are intended to be achievable

with good practice as centers become proﬁcient at rou-

tinely performing endovascular therapies, and provide

a benchmark for QI in current clinical practice.

Moreover, many of the conditions and ﬁndings that,

in the past, could have complicated decision-making,

such as older age, extracranial carotid obstruction,

vessel tortuosity, requirement for penumbral imaging,

and requirement for general anesthesia, did not nega-

tively inﬂuence treatment eﬀect and should not delay

the decision for treatment. The treatment of more com-

plex cases than were included in the trials may prolong

treatment times but should not prolong the time to

arterial puncture.

As a general approach to setting metrics for care

processes, we used data from the HERMES collabor-

ation (46). The 75th-percentile times (ie, slowest quar-

tile) are considered minimum benchmarks, and the

25th-percentile times (ie, fastest quartile) from that

study are considered achievable by the best centers

with high volumes and good resource infrastructure.

The metrics are intended to be used for measurements

such that centers will progressively become faster and

improve times from minimum acceptable to ideal.

The times reported in the following sections apply to

anterior circulation occlusions, as vertebrobasilar

occlusions were excluded in the recent randomized

trials. These metrics should be applicable regardless

of the time of the day and regardless of whether the

patient presents on a weekday versus a weekend (103).

These metrics represent maximum recommended times.

Because of ample evidence that, the shorter the time to

reperfusion, the higher the likelihood of a favorable

outcome, all centers should strive to initiate endovas-

cular therapy within the shortest possible time frame.

Although intravenous TPA administration should not

represent a justiﬁcation for excessive delays in initiation

of endovascular therapy, it is acknowledged that intra-

venous thrombolysis may be associated with some

delays in initiation of endovascular therapy.

Door to imaging.—Most hospitals will use CT-based

imaging, but some hospital protocols may use MR ima-

ging as the ﬁrst imaging study. The use of CT angiog-

raphy or MR angiography for vascular imaging is

considered the standard of care for endovascular treat-

ment based on recent trials and should be incorporated

into the imaging protocol. Indeed, previously published

guidelines on imaging in acute stroke patients (104)

recommend that noninvasive vascular imaging be rou-

tinely performed, and it is recognized that the use of

advanced multimodal imaging does not delay treatment

times (105). Regardless of the choice of modality based

on institutional preferences, imaging should be started as

quickly as feasible. Because of the diﬃculty in deﬁning

exactly when an order might have been entered in the

system, this document is in agreement with the

American Stroke Association recommendations that

these time intervals be measured from arrival to start of

imaging, which will also include vascular imaging.

Interpretation of imaging is done in parallel and usually

at the scanner by the treating team, and the time needed

to interpret the scans and make a decision will be part of

the overall time from the start of imaging to arterial

puncture. In the HERMES meta-analysis (46), the fastest

25% of cases had imaging initiated by 12 minutes, and

75% of patients had imaging initiated within 30 minutes.

Metric 3: 75% of patients being evaluated for revascu-

larization should have imaging initiated within 30 min-

utes from time of arrival. At the best of centers with

high volumes and an established resource infrastruc-

ture, this is expected to be achieved in 12 minutes.

Imaging to puncture.—The largest amount of time

from door to revascularization comes from the steps

from door to puncture rather than puncture to revas-

cularization, and most endovascular treatment deci-

sions are made after imaging. Therefore, the largest

opportunities to reduce delays and improve outcomes

will come from reducing imaging-to-puncture times.

The recommended time from start of imaging to arter-

ial puncture is 50 minutes or less. This is in keeping

with the time intervals reported in the recent endovas-

cular trials, which had a fastest 25th percentile of 51

minutes (46), and it is the consensus of the writing

group that this time metric is necessary, achievable,

and consistent with the improvement in door-to-bal-

loon times that have been achieved for acute myocar-

dial infarction. The recent trials also reported that 75%

of patients had an imaging-to-puncture time of no more

than 110 minutes. For patients transferred from

another site whose imaging does not need to be

repeated, it is expected that door-to-puncture times

can be reduced by 30 minutes.

Metric 4: 75% of patients treated with endovascular

therapy should have an imaging-to-puncture time of

110 minutes or less. At the best of centers with high

volumes and an established resource infrastructure, this

is expected to be achieved in 50 minutes or less.

Metric 5: For patients transferred from another site in

whom imaging is not repeated, 75% of patients being

treated should have a door-to-puncture time of 80 min-

utes or less.

International Journal of Stroke, 0(0)

Sacks et al. 9

Imaging-to-thrombus time.—Previous versions of this

document have included imaging-to-thrombus time as a

metric. This is no longer believed to be a necessary time

point for measurement as a result of inaccuracies of

measurement and inconsistent practice in documenting

the same.

Puncture time to reperfusion.—This metric assesses

the eﬃciency of the interventional physician and

team. Given the rapid advancements in endovascular

treatment modalities, these recommendations are

likely to change. In the Mechanical Embolus

Removal in Cerebral Ischemia registry (41), the largest

prospective endovascular database to date reﬂecting

procedural outcomes across a large variety of stroke

centers in the United States, the median time from

groin puncture to the end of the procedure was 90 min-

utes. Newer technologies such as ‘‘stentrievers’’ have

been noted to achieve signiﬁcantly shorter procedural

times (median of approximately 50 min) (46).

Although time to ﬁnal angiography is easily mea-

sured, it may be variable depending on the need to per-

form thrombolysis of peripheral-branch occlusions

after recanalization of the proximal occlusion, as

more complete revascularization is likely to lead to

improved clinical outcomes, albeit at some increased

procedural risk. The time metric described here for suc-

cessful reperfusion represents the time to ﬁrst reach an

mTICI grade 2b. Additional time, if required to

achieve complete revascularization, ie, mTICI grade

3, is not reﬂected in this metric. Recent trials have pub-

lished their time intervals, and, by doing so, set new

expectations. Median time from groin puncture to

reperfusion in the SWIFT PRIME trial (20) was 24

minutes (interquartile range, 18–33 min). The median

puncture-to-reperfusion time in the HERMES collab-

oration (46) was 44 minutes (interquartile range, 27–

64.5 min). Generally, we recommend that procedure

times not exceed 60 minutes as in the recent trials,

and the reperfusion target should be to reach mTICI

grade 2b (20). This threshold is further clariﬁed in the

following section on recanalization/reperfusion.

Metric 6: In 70% of patients, mTICI grade 2b should

be reached ideally within 60 minutes of arterial

puncture.

Recanalization/Reperfusion

Revascularization is key to improving outcomes with

endovascular stroke therapy. Recanalization of the

occluded vessel and reperfusion of the distal capillary

bed are measures of revascularization, and, although

intimately linked, are not necessarily interchangeable.

Of the two measures, reperfusion of the distal capillary

bed is most linked with clinical outcome (106).

Reperfusion can be assessed by using CT or MR per-

fusion imaging. On angiography, crude assessment of

reperfusion can be made by assessing blood ﬂow into

the distal bed, but this does not necessarily correlate

with reperfusion on a microcirculatory level (106).

Although advances have been made in perfusion assess-

ment in the angiographic suite (107), this assessment is

not readily available at the present time. Therefore,

most interventionalists will rely on a combination of

recanalization and reperfusion to assess

revascularization.

Revascularization can be assessed in a number of

ways, including the thrombolysis in cerebral infarction

(TICI) scale (108), the thrombolysis in myocardial

infarction (TIMI) scale (109,110), the Mori reperfusion

scale (111), the Qureshi scale (112), and the Arterial

Occlusive Lesion score (113), among others. No direct

comparisons of the revascularization scales in terms of

their predictive ability for ﬁnal infarct volume exist,

but, through expert comparison of scales, the stroke

and interventional community favors the use of the

TICI scale (114,115). In a comparison of TIMI versus

TICI scales, TICI was found to be superior to TIMI.

The mTICI scale (Table 1) shifted the deﬁnition of a

grade of 2b to reperfusion of >50% rather than >66%

of the distal territory (31), and mTICI grade 2b/3 was

used as the deﬁnition of procedural success in the

majority of the successful endovascular trials. This is

the scale recommended for future studies (30). A fur-

ther reﬁnement to the TICI scale introduced a new cat-

egory of 2c to deﬁne angiographic revascularization

of >90% and <100% of the distal territory (116).

However, the clinical applicability of TICI grade 2c

has not been validated in larger prospective trials.

Nevertheless, the higher the recanalization and reperfu-

sion grade, the better the outcome, with particularly

improved outcomes seen with grades of 2b or higher

(116) and the best outcomes seen with TICI grade 3

revascularization (117).

Compared with earlier studies (9,17), the positive

clinical trials of endovascular stroke therapy showed

vastly improved revascularization rates, with mTICI

grade 2b/3 rates ranging from 58.7% to 88.0%

(7,11,13,15,20), and the HERMES meta-analysis (14)

found an mTICI grade 2b/3 rate of 71%. The

THERAPY trial (18) reported an mTICI grade 2b/3

rate of 73%. This was assessed with the use of core

laboratory adjudication in most studies, and it has

been shown that local sites tend to overestimate the

degree of reperfusion compared with a core laboratory

(99). Postmarket registries have found mTICI

grade 2b rates of 70.9%–73.9%, but no central adju-

dication was performed (97,118,119). Based on this, an

mTICI grade 2b rate of 70% seems a reasonable

International Journal of Stroke, 0(0)

10 International Journal of Stroke 0(0)

number for all acute ischemic strokes treated. Only

moderate agreement exists between raters for the

TICI scale, even though agreement is substantial

when the scale is dichotomized into successful (ie,

TICI grade 2b/3) or unsuccessful outcomes (ie, TICI

grade 0, 1, or 2a) (120).

In terms of technical success of procedures, it is also

important to note the presence of distal embolization

and embolization to new territory (31). The ultimate

goal of revascularization is to improve patient out-

comes. However, there is a risk that persistent attempts

to recanalize an occlusion may lead to more complica-

tions. The combined metrics for SICH, revasculariza-

tion, and mRS scores of 0–2 measure these risks and

beneﬁts.

Metric 7: The mTICI scale should be the primary scale

used to assess angiographic reperfusion.

Metric 8: At least 70% of patients should have mTICI

grade 2b/3 (ie, >50%) reperfusion for all clot locations.

Postprocedural CT/MR Imaging

Postprocedural imaging is necessary to identify acute

SAH or parenchymal hematoma, diﬀerentiate intrapar-

enchymal hemorrhage from contrast staining, deﬁne

the overall extent of new stroke, and identify other

ﬁndings. Although there is no evidence that this

improves clinical outcomes, there is consensus based

on European guidelines that postprocedural imaging

is required (121). CT or MR imaging within 36 hours

after intervention should be performed in all stroke

patients (7,11,15,20). Although some patients may

receive CT or MR imaging immediately after the pro-

cedure, imaging performed the next day provides add-

itional valuable information. It is recognized that there

are certain circumstances that might render follow-up

imaging diﬃcult or impossible to perform. Therefore,

the threshold for this imaging is 90%, acknowledging

that a goal of 100% is desired.

Metric 9: At least 90% of patients should have a brain

CT or MR imaging examination within 36 hours of the

end of the procedure.

SICH

The most common major risk of endovascular treat-

ment of acute ischemic stroke is SICH. As deﬁned by

individual studies, the incidences of SICH following

endovascular revascularization range from 2% to

10% for combined intravenous and intraarterial

thrombolytic trials (9,12,39,122) and from 1% to 8%

for EVT trials (7,11,13,20,121). Several deﬁnitions have

been used, as described in the National Institute of

Neurological Disorders and Stroke trial (1), the SITS-

MOST (33) and INSTOR registries (78), and European

registries such as SITS-Thrombectomy (32,81), MR

CLEAN (82) (Netherlands), and the Heidelberg

Bleeding Classiﬁcation (34).

SAH is a unique complication of endovascular ther-

apy and is not typically seen with intravenous therapy

with TPA alone. Intraprocedural SAH caused by arter-

ial perforation can be rapidly fatal, but has been

described as being asymptomatic in as many as 16%

of patients treated with mechanical thrombectomy

without perforation (123).

The deﬁnition chosen for SICH in this document is

based on that used by the SWIFT PRIME trial (20) and

includes any intracranial hemorrhage with neurologic

deterioration leading to an increase in NIHSS score >4

or leading to death within 24 hours of treatment.

SICH is not only an ‘‘end-result’’ evaluation of clin-

ical judgment in the realm of patient selection and tech-

nical skill, but also a reﬂection of timing, procedural

execution, and expeditious completion of the task. For

these reasons, tracking of SICH is mandatory.

Metric 10: 100% of cases with SICH are reviewed (see

Quality Improvement).

Metric 11: No more than 10% of treated patients

should develop SICH.

Embolization of New Territory

Embolization of previously unaﬀected territories and

embolization as a result of clot fragmentation within

the treated territory can occur during endovascular

treatment. Distal embolization within the treated terri-

tory is diﬀerent from embolization of new territory and

has been reported in 16% of patients treated with endo-

vascular thrombolysis and 35% of patients treated with

thrombectomy, without decreasing the likelihood of a

favorable outcome (124,125). Embolization of new ter-

ritory has been reported in 5%–9% of patients treated

in the recent EVT trials (7,13,20) and may cause new

areas of symptomatic infarct or require additional

treatment of previously unaﬀected vessels.

Metric 12: No more than 10% of patients should have

embolization of new territory.

Death within 72 Hours of Treatment

Death within 72 hours of stroke is typically not a result

of the stroke itself. The authors clearly acknowledge

International Journal of Stroke, 0(0)

Sacks et al. 11

that every case is unique and that each instance needs to

be reviewed in its entirety with the understanding that

there are circumstances (eg, myocardial infarction) that

lead to death in the short term and are unrelated to

operator factors. Death soon after a procedure in and

of itself does not imply or indicate a quality problem.

However, all deaths within 72 hours are a trigger for

review.

Metric 13: 100% of cases of death within 72 hours of

the end of the procedure are reviewed.

Clinical Outcomes

Ultimately, the goal of endovascular stroke therapy is

to limit the size and extent (ie, severity) of stroke,

improve the clinical outcome of the patient, and pre-

vent long-term disability. By convention, these out-

comes are commonly assessed by using various

functional grading systems: during initial hospitaliza-

tion, stroke is commonly assessed based on changes

in the NIHSS score, and then, often at 90 days, by

using the mRS. Clinical outcomes of stroke revascular-

ization are multifactorial, depending on factors intrin-

sic to the patient such as preexisting cerebral artery

collateral vessels, procedural factors such as time to

revascularization and completeness of revasculariza-

tion, as well as the patient’s response to a host of inter-

ventions in intensive care and then rehabilitation.

Among speciﬁc patient factors, higher admission

NIHSS scores and age were shown in the HERMES

meta-analysis (14) to portend worse outcomes with

medical or endovascular therapy. Other medical

comorbidities such as underlying cardiac disease,

hypertension, and diabetes mellitus all play a role in

outcomes. From a procedural standpoint, higher rates

of recanalization are associated with improved out-

comes. A key component of any interventional stroke

program is tracking of clinical outcomes. To that end,

we propose that a discharge NIHSS score be docu-

mented on all patients, and that all patients are con-

tacted and evaluated to obtain an mRS score at 90

days. Early improvement in NIHSS score may function

as a surrogate marker of outcome in situations in which

an mRS score cannot be obtained (126,127). Although

it is ideal to assess the patient in person, this may not

always be possible, and telephone assessment of mRS

score is a reasonable alternative that is well validated

(128). We understand that some patients may be lost to

follow-up by 90 days.

Metric 14: All treated patients have a documented

NIHSS score 20–36 hours after treatment and at dis-

charge. Attempts are made to contact and document a

follow-up mRS score at 90 days (evaluated in person or

via telephone) on all treated patients. At least 90% of

treated patients have documented 90-day mRS score.

Determining a single threshold level of ‘‘good clinical

outcome’’ for all patient populations is diﬃcult because

of the heterogeneity of treated patients and the absence

of comprehensive data. Individual centers, for example,

may have a more elderly patient population or patients

with later presentations. The incidences of patients with

an mRS score of 0–2 at 90 days in the recent rando-

mized controlled endovascular trials ranged from 33%

(MR CLEAN) (7) to 71% (EXTEND-IA) (11), with an

overall aggregate rate of 46% in the HERMES trial

(14). Similarly, the THERAPY (18) and Trial and

Cost Eﬀectiveness Evaluation of Intra-arterial

Thrombectomy in Acute Ischemic Stroke (THRACE)

(8) trials reported 38% and 53% rates of mRS score 0–

2 at 90 days, respectively, and, in the per-protocol

population of the Pragmatic Ischaemic

Thrombectomy Evaluation (PISTE) trial (129), 57%

of the endovascular group reached an mRS score of

0–2 at 90 days.

The major trials focused on stroke patients with

large artery occlusions, speciﬁcally internal carotid ter-

minus or proximal middle cerebral (ie, M1) arteries.

However, some patients with severe stroke have occlu-

sions at other locations. Patients with isolated M2

branch occlusions may be reasonable candidates for

EVT, but, in general, the natural history of stroke in

these patients is better than those with more proximal

occlusions (130). Although there are no randomized

data showing a beneﬁt for thrombectomy in basilar

artery occlusions, these are often treated at many cen-

ters (131). Several studies have speciﬁcally reported

worse outcomes for patients who did not meet the

trial inclusion criteria or the current American Heart

Association level IA recommendations (22). Gratz et al

(119) reported 30% versus 57% incidences of mRS

score of 0–2 for high-risk patients versus standard-

risk patients. Similarly, Goyal et al (75) reported 39%

versus 47% incidences of mRS score of 0–2 for patients

not meeting versus meeting AHA level I

recommendations.

One must take prestroke functional status into

account when setting a threshold for 90-day mRS

score for good outcome. The vast majority of patients

in the recent randomized trials had an mRS score of 0/1

at baseline. As described in the Indications section, this

is not to imply that EVT be withheld for those who do

not have an mRS score of 0/1, but that any outcome

threshold needs to account for prestroke functional

status.

Multicenter registries have reported results with

modern thrombectomy in more heterogenous groups

International Journal of Stroke, 0(0)

12 International Journal of Stroke 0(0)

of patients, including patients with vertebrobasilar and

M2 clot locations as well as tandem lesions. The regis-

tries include the German Register on Revascularization

in Ischemic Stroke Patients (REVASK) registry

(N ¼1,107 patients, 40% mRS score 0–2 at 90 d)

(132), the Catalonia stroke registry (N ¼536 patients,

43% mRS score 0–2 at 90 d) (118), the North American

Solitaire registry (N ¼354 patients, 42% mRS score 0–

2 at 90 d) (133), and the Madrid registry (N ¼479, 54%

mRS score 0–2 at 90 d) (131). The Dutch MR CLEAN

registry (134) reported a 41% incidence of mRS score

0–2 at 90 days in a group of 1,321 patients. Compared

with the randomized trials, the registries will include

some patients at higher risk (ie, basilar occlusions),

some at lower risk (ie, M2 occlusions), and some

biased data, as the data are not adjudicated, likely lead-

ing to better reported outcomes. However, this is likely

to be similar to the experiences of hospitals using the

metrics of this document.

Clinical acumen is needed to determine the risk

versus beneﬁt of treatment based on published trial

and registry data and personal experience. The AHA

has created level I recommendations (22) for patient

selection based on current randomized trials.

However, we expect these recommendations to evolve

as results from trials address ‘‘wake-up’’ strokes, pro-

longed time from symptom onset, basilar artery occlu-

sions, large infarct size, and ‘‘mothership’’ versus ‘‘drip-

and-ship’’ cases (48,49,54,55,59,135).

We propose a single threshold for clinical outcomes

for all treated patients regardless of whether they would

have been candidates for the majority of recent trials or

meet the AHA level I recommendations. This is con-

sistent with the heterogeneity of current clinical practice

in which nearly half of treated patients do not meet the

AHA recommendations (75). This document does not

advocate for or against treating patients outside of the

randomized trial or AHA level I recommendations, but

suggests a threshold that recognizes the common prac-

tice of treating such patients. The threshold of a 30%

incidence of mRS score of 0–2 at 90 days is lower than

those of the recent randomized trials and registries

based on the experience that ‘‘oﬀ-trial’’ patients are

more likely to be at higher risk for poor outcomes

(75,119) and the belief that the published registry

results may not reﬂect the most current trends in

patient selection. It is important to note that, although

achieving an mRS score of 0–2 is an important goal, it

is not the only marker of a favorable outcome after

endovascular therapy. Some patients may have import-

ant clinical beneﬁt with an mRS score shift from 4/5

down to 3. However, mRS score shift analysis requires

a control group comparison, which is not useful as a

quality metric. This suggested threshold should not dis-

suade centers from treating individual patients if they

believe there is a potential beneﬁt from the procedure.

Given the multiple factors that inﬂuence outcomes, cen-

ters are encouraged to benchmark their outcomes

against those from a similar patient population.

The clinical outcome threshold of this document is

intended to prompt internal review of the endovascular

stroke program. It is not designed to constitute a stand-

ard for reimbursement from payers, or for accreditation

purposes. Local patient factors such as overall medical

comorbidities and time from symptom onset to treat-

ment should be taken into account when reviewing any

single institution’s performance. This is especially true

in those patients who have a greater degree of prestroke

disability or other comorbidities that may have

excluded them from the recent randomized trials, but

for whom treatment may be warranted.

Metric 15: Of all treated patients, at least 30% are inde-

pendent (ie, mRS score 0–2) at 90 days after treatment.

Quality improvement

Ongoing Quality Improvement

As EVT of acute ischemic stroke becomes a mainstream

oﬀering at many centers, an endovascular-speciﬁc

multidisciplinary QI process should be established in

all programs oﬀering this treatment (24,25). These

endovascular cases, similar to trauma cases, require

complex processes of care. These processes go beyond

the clinical and technical skills of the operators them-

selves and should be monitored in a continuous and

ongoing fashion.

A peer-review committee at the local hospital should

be formed that involves personnel from the several

backgrounds that have expertise in stroke care as well

as a vested interest in quality of care and outcomes.

This committee should provide an open and transpar-

ent forum for process and case review. Transparency

will optimize conﬁdence in the process, which should

have a positive impact on patient care. Although there

may be potential for conﬂict or disagreement among

various participants, it is vital that the process be

viewed as a nonpolitical, nonpunitive instrument for

care process improvement.

Speciﬁcally within the United States, in keeping with

standards established under the Health Care Quality

Improvement Act of 1986 (42 USC §11101 et seq.),

peer-review meetings and minutes are generally pro-

tected from legal inquiry in most states as long as the

review is conducted under the auspices of the facility QI

program. The Health Care Quality Improvement Act

established standards for professional review actions.

Although this protection is not absolute, if a

International Journal of Stroke, 0(0)

Sacks et al. 13

professional review body meets these standards, neither

the professional review body nor any person acting as a

member or staﬀ to the body will be liable for damages

under most federal or state laws with respect to the

action (136–139). All associated QI documents should

include routine annotation that establishes the purpose

of the document and that its content is protected under

applicable federal or state law. The program should

operate under the local facility umbrella established

for all facility QI and peer-review initiatives.

Peer Review Team

It is recommended that, under the oversight of the stroke

team medical director, a predetermined multidisciplin-

ary subgroup consisting of medical personnel with

familiarity and expertise in endovascular therapy be

established to address issues speciﬁcally relating to endo-

vascular treatment. Although a stroke neurologist is

generally in the best overall position to objectively

assess overall process deﬁciencies and outcomes, for

technical and procedural issues, an interventionalist per-

spective must be considered. Ideally, the endovascular

oversight team should be directed by a highly qualiﬁed

and unbiased physician such as a noninterventional vas-

cular neurologist. Depending on the institution, the

endovascular QI peer group could include a variable

combination of interventionalists, vascular neurologists,

cerebrovascular neurosurgeons, intensivists, and diag-

nostic neuroradiologists. Additional members might

include hospital representative(s) from the quality assur-

ance/improvement or risk management departments, as

well as possibly the stroke coordinator or other data

personnel and secretarial support staﬀ.

Review Process

The endovascular QI meeting should occur at least

quarterly, and, depending on volume, may need to

occur more frequently to provide adequate assessment

and review. There should be review of every case in

centers with volumes <50 cases per year and review

of every case in which the parameters are outside the

benchmarks (eg, prolonged time to puncture, failure of

reperfusion, prolonged time to reperfusion) or in which

a complication occurs (eg, SICH, embolization of new

territory, or death within 72 h). As noted earlier in the

section on data collection, all cases should be entered

into a trial, database, or registry with national partici-

pation (24,25,76). In the United States, Medicare is

functioning under the Medicare Access and Children’s

Health Insurance Program Reauthorization Act of

2015 (140), which seeks to align disparate quality pro-

grams through Qualiﬁed Clinical Data Registries. This

approach is in keeping with our aforementioned

recommendation for data collection and quality control

(141,142).

The interventionalist who performed the speciﬁc

case under review should be present to oﬀer his/her

observations and perspective. The focused endovascu-

lar peer review should routinely include assessment of

technical factors such as device choice, supplemental

lytic agent infusion, and equipment inventory assess-

ment. Process elements such as on-call notiﬁcation,

timing (ie, door-to-imaging and imaging–to–arterial

puncture times), procedure table setup, and overall

communication should also receive routine attention.

Performance review is not limited to the treating endo-

vascular physician, but should also include the emer-

gency department, neurology and neurointensive care

personnel, interventional technologists, nursing staﬀ,

and other related service areas as indicated.

Information concerning transfer from and communica-

tion with referring primary stroke centers before and

after return to the primary center, complications, and

90-day functional outcome should also be routinely dis-

cussed and benchmarked.

Triggers for Review

Any event that might aﬀect quality should be reviewed.

Speciﬁc triggers for endovascular review include unmet

process benchmarks, death, and symptomatic postpro-

cedural hemorrhage. Some complications or process

delays may be unavoidable, whereas others may reﬂect

signiﬁcant errors in judgment or process deﬁciencies.

A determination must be made if the patient was

harmed. Process problems such as delays or inadequate

communication increase the risk of harm. Therefore,

complications and events that increase the risk of

poor outcomes need to be reviewed as a means of

improving quality. There must also be diﬀerentiation

between clearly procedure-related complications (eg,

perforation and/or dissection, distal dislodgment of

thrombus that remains unreachable, embolization of

new territory, and immediate SICH following the pro-

cedure) and those that might be related to the primary

ischemic event itself (eg, infarction, cerebral edema, and

hemorrhagic transformation). Predisposing underlying

vascular disease and comorbidities must also be

considered.

Physicians who choose to treat sicker patients may

have poorer outcomes and may not meet established

benchmarks. These cases should not be considered in

isolation, as a poor outcome does not necessarily indi-

cate that such physicians are providing a lower quality

of care, but rather that they have a diﬀerent patient mix

than the trials that were used to create the benchmarks

(7,8,10,11,13–15,18,20,143–145). Adjusting for risk and

severity may be helpful in assessing local outcomes

International Journal of Stroke, 0(0)

14 International Journal of Stroke 0(0)

Table 3. Endovascular Therapy Quality Improvement Case Review Triggers and Process Metrics

Indications for Endovascular Treatment

Metric 1: At least 90% of patients who meet the institution selection criteria (indications/contraindications) should be treated

with endovascular therapy.

Data Collection

Metric 2: 100% of patients have the required minimum process and outcomes data entered into an institutional or national

database, trial, or registry.

Key Time Intervals

Door to imaging

Metric 3: 75% of patients being evaluated for revascularization should have imaging initiated within 30 minutes from time of

arrival. At the best of centers with high volumes and an established resource infrastructure, this is expected to be achieved in

12 minutes.

Imaging to puncture

Metric 4: 75% of patients treated with endovascular therapy should have an imaging-to-puncture time of 110 minutes or less. At

the best of centers with high volumes and an established resource infrastructure, this is expected to be achieved in 50 minutes

or less.

Metric 5: For patients transferred from another site and in whom imaging is not repeated, 75% of patients being treated should

have a door-to-puncture time of 80 minutes or less.

Puncture to revascularization

Metric 6: In 70% of patients, mTICI score 2b should be reached ideally within 60 minutes of arterial puncture.

Outcome Metrics

Recanalization/reperfusion

Metric 7: The mTICI scale should be the primary scale used to assess angiographic reperfusion.

Metric 8: At least 70% of patients should have an mTICI score 2b/3 (>50% reperfusion) for all clot locations.

Postprocedure CT/MR Imaging

Metric 9: At least 90% of patients should have a brain CT or MR imaging within 36 hours of the end of the procedure.

SICH

Metric 10: 100% of cases with SICH are reviewed.

Metric 11: No more than 10% of treated patients should develop SICH.

Embolization of new territory

Metric 12: No more than 10% of patients should have embolization of new territory.

Death within 72 hours of treatment

Metric 13: 100% of cases of death within 72 hours of the end of the procedure are reviewed.

Clinical Outcomes

Metric 14: All treated patients have a documented NIHSS score at discharge. Attempts are made to contact and document a

follow-up mRS score at 90 days (evaluated in person or via telephone) on all treated patients. At least 90% of treated patients

have a documented 90-day mRS score.

Metric 15: Of all treated patients, at least 30% are independent (ie, mRS score 0–2) at 90 days after treatment.

mRS: modified Rankin scale; mTICI: modified thrombolysis in cerebral infarction; NIHSS: National Institutes of Health Stroke Scale; SICH: symptomatic

intracranial hemorrhage.

International Journal of Stroke, 0(0)

Sacks et al. 15

compared with other institutions and benchmarks.

Endovascular QI case review triggers and key process

metrics are summarized in Table 3.

In addition to these morbidity and mortality mar-

kers, it is incumbent on the institution and the quality-

assurance/improvement and peer-review committee to

also assess the ‘‘good outcomes.’’ A certain percentage

of good outcomes are necessary for there to be suﬃ-

cient beneﬁt to the overall patient population. This

document also deﬁnes minimal recanalization rates as

well as improved clinical outcomes that should be

attained.

Performance and Process Improvement

The committee should be equipped to deal with poor

performance in a supportive, constructive, and collegial

manner. In cases in which negative trends and deﬁcien-

cies become apparent, improvement may require indi-

vidual mentoring, additional education, or

supplemental training. Endovascular stroke QI review

of problematic cases should generate a speciﬁc course

of action to remedy recognized problems and prevent

future occurrences. Individual assignments should be

tracked, with accountability reports scheduled for sub-

sequent meetings. Further, process improvement is a

continuing activity that, along with individual perform-

ance improvement, will signiﬁcantly impact clinical

outcomes (146).

Acknowledgments

The authors thank Zachary Zhang, MD (Rochester General

Hospital, Rochester, New York), for assistance creating the

evidence table and formatting the document; and Sean A.

Kennedy, MD (University of Toronto, Toronto, Ontario),

and Ajinkya Desai, MD (Rochester General Hospital,

Rochester, New York), for assistance creating the

evidence table.

Declaration of Conflicting Interests

The author(s) declared the following potential conﬂicts of

interest with respect to the research, authorship, and/or pub-

lication of this article: B.B. receives personal fees from

Penumbra (Alameda, California), Medtronic (Dublin,

Ireland), Stryker (Fremont, California), and Pulsar Vascular

(Los Gatos, California) and has a patent (US8622992) issued

to Advanced Catheter Therapies (Chattanooga, Tennessee).

C.C. receives personal fees from Microvention (Tokyo,

Japan), Stryker, Medtronic, and Balt (Montmorency,

France). D.D. receives grants from the Dutch Heart

Foundation, AngioCare (Eemnes, The Netherlands),

Medtronic/Covidien/ev3 (Dublin, Ireland), Medac/Lamepro

(Breda, The Netherlands), Penumbra, Top Medical/

Concentric (New York, New York), and Stryker. U.F.

receives grants from the SWIFT DIRECT study and personal

fees from Medtronic. J.A.H. receives personal fees from

Medtronic, Globus (Audubon, Pennsylvania), and Codman

Neuro (Raynham, Massachusetts). C.M.S. receives grants

from the National Institutes of Health/National Institute of

Neurological Disorders and Stroke, Medtronic, and

Penumbra and personal fees from Toshiba (Otawara,

Japan) and ExpertiCas (Southport, Connecticut) and is a

stockholder in Neurotechnology Investors (Palo Alto,

California). None of the other authors have identiﬁed a con-

ﬂict of interest.

Supplementary Material

Table E1 is available online at www.jvir.org.

References

1. Tissue plasminogen activator for acute ischemic stroke.

The National Institute of Neurological Disorders and

Stroke rt-PA Stroke Study Group. N Engl J Med 1995;

333: 1581–1587.

2. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease

and stroke statistics–2015 update: a report from the

American Heart Association. Circulation 2015; 131:

e29–e322.

3. Gibson CM, Pride YB, Frederick PD, et al. Trends in

reperfusion strategies, door-to-needle and door-to-bal-

loon times, and in-hospital mortality among patients

with ST-segment elevation myocardial infarction enrolled

in the National Registry of Myocardial Infarction from

1990 to 2006. Am Heart J 2008; 156: 1035–1044.

4. Sacks D, Black CM, Cognard C, et al. Multisociety con-

sensus quality improvement guidelines for intraarterial

catheter-directed treatment of acute ischemic stroke,

from the American Society of Neuroradiology,

Canadian Interventional Radiology Association,

Cardiovascular and Interventional Radiological Society

of Europe, Society for Cardiovascular Angiography and

Interventions, Society of Interventional Radiology,

Society of NeuroInterventional Surgery, European

Society of Minimally Invasive Neurological Therapy,

and Society of Vascular and Interventional Neurology.

J Vasc Interv Radiol 2013; 24: 151–163.

5. White PM, Bhalla A, Dinsmore J, et al. Standards for

providing safe acute ischaemic stroke thrombectomy ser-

vices (September 2015). Clin Radiol 2017; 72: 175.e1–e9.

6. Badhiwala JH, Nassiri F, Alhazzani W, et al.

Endovascular thrombectomy for acute ischemic stroke:

a meta-analysis. JAMA 2015; 314: 1832–1843.

7. Berkhemer OA, Fransen PS, Beumer D, et al. A rando-

mized trial of intraarterial treatment for acute ischemic

stroke. N Engl J Med 2015; 372: 11–20.

8. Bracard S, Ducrocq X, Mas JL, et al. Mechanical

thrombectomy after intravenous alteplase versus alte-

plase alone after stroke (THRACE): a randomised con-

trolled trial. Lancet Neurol 2016; 15: 1138–1147.

9. Broderick JP, Palesch YY, Demchuk AM, et al.

Endovascular therapy after intravenous t-PA versus t-

PA alone for stroke. N Engl J Med 2013; 368: 893–903.

10. Campbell BC, Hill MD, Rubiera M, et al. Safety and

efficacy of solitaire stent thrombectomy: individual

International Journal of Stroke, 0(0)

16 International Journal of Stroke 0(0)

patient data meta-analysis of randomized trials. Stroke

2016; 47: 798–806.

11. Campbell BC, Mitchell PJ, Kleinig TJ, et al.

Endovascular therapy for ischemic stroke with perfu-

sion-imaging selection. N Engl J Med 2015; 372:

1009–1018.

12. Ciccone A, Valvassori L, Nichelatti M, et al;

SYNTHESIS Expansion Investigators. Endovascular

treatment for acute ischemic stroke. N Engl J Med

2013; 368: 904–913.

13. Goyal M, Demchuk AM, Menon BK, et al. Randomized

assessment of rapid endovascular treatment of ischemic

stroke. N Engl J Med 2015; 372: 1019–1030.

14. Goyal M, Menon BK, van Zwam WH, et al.

Endovascular thrombectomy after large-vessel ischaemic

stroke: a meta-analysis of individual patient data from

five randomised trials. Lancet 2016; 387: 1723–1731.

15. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy

within 8 hours after symptom onset in ischemic stroke.

N Engl J Med 2015; 372: 2296–2306.

16. Kennedy SA, Baerlocher MO, Baerlocher F, et al. Meta-

analysis of local endovascular therapy for acute ischemic

stroke. J Vasc Interv Radiol 2016; 27: 307–321.

17. Kidwell CS, Jahan R, Gornbein J, et al. A trial of ima-

ging selection and endovascular treatment for ischemic

stroke. N Engl J Med 2013; 368: 914–923.

18. Mocco J, Zaidat OO, von Kummer R, et al. Aspiration

thrombectomy after intravenous alteplase versus intra-

venous alteplase alone. Stroke 2016; 47: 2331–2338.

19. Prabhakaran S, Ruff I and Bernstein RA. Acute stroke

intervention: a systematic review. JAMA 2015; 313:

1451–1462.

20. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever

thrombectomy after intravenous t-PA vs. t-PA alone in

stroke. N Engl J Med 2015; 372: 2285–2295.

21. NICE Interventional Procedure Guidance. Mechanical

clot retrieval for treating acute ischaemic stroke.

Interventional procedures guidance [IPG548], February

2016. Available at: http://www.nice.org.uk/guidance/

ipg548. Accessed April 10, 2016.

22. Powers WJ, Derdeyn CP, Biller J, et al. 2015 American

Heart Association/American Stroke Association focused

update of the 2013 guidelines for the early management

of patients with acute ischemic stroke regarding endovas-

cular treatment: a guideline for healthcare professionals

from the American Heart Association/American Stroke

Association. Stroke 2015; 46: 3020–3035.

23. Wahlgren N, Moreira T, Michel P, et al. Mechanical

thrombectomy in acute ischemic stroke: consensus state-

ment by ESO-Karolinska stroke update 2014/2015, sup-

ported by ESO, ESMINT, ESNR and EAN. Int J Stroke

2016; 11: 134–147.

24. Connors JJ III, Sacks D, Black CM, et al. Training guide-

lines for intra-arterial catheter-directed treatment of

acute ischemic stroke: a statement from a special writing

group of the Society of Interventional Radiology. J Vasc

Interv Radiol 2009; 20: 1507–1522.

25. Lavine SD, Cockroft K, Hoh B, et al. Training guidelines

for endovascular ischemic stroke intervention: an

international multi-society consensus document. AJNR

Am J Neuroradiol 2016; 37: E31–E34.

26. Jovin TG, Albers GW and Liebeskind DS; STAIR IX

Consortium. Stroke treatment academic industry round-

table: the next generation of endovascular trials. Stroke

2016; 47: 2656–2665.

27. Fink A, Kosecoff J, Chassin M and Brook RH.

Consensus methods: characteristics and guidelines for

use. Am J Public Health 1984; 74: 979–983.

28. Institute of Medicine (U.S.) Committee on Standards for

Developing Trustworthy Clinical Practice Guidelines.

Clinical Practice Guidelines We Can Trust. Graham R,

Mancher M, Wolman DM, Greenfield S, Steinberg E,

eds. Washington, DC: National Academies Press, 2011.

xxxiv.

29. Sacco RL, Kasner SE, Broderick JP, et al. An updated

definition of stroke for the 21st century: a statement for

healthcare professionals from the American Heart

Association/American Stroke Association. Stroke 2013;

44: 2064–2089.

30. Wintermark M, Albers GW, Broderick JP, et al. Acute

stroke imaging research roadmap II. Stroke 2013; 44:

2628–2639.

31. Zaidat OO, Yoo AJ, Khatri P, et al. Recommendations

on angiographic revascularization grading standards for

acute ischemic stroke: a consensus statement. Stroke

2013; 44: 2650–2663.

32. Wahlgren N, Ahmed N, Eriksson N, et al. Multivariable

analysis of outcome predictors and adjustment of main

outcome results to baseline data profile in randomized

controlled trials: safe implementation of thrombolysis in

stroke-monitoring study (SITS-MOST). Stroke 2008; 39:

3316–3322.

33. Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis

with alteplase for acute ischaemic stroke in the safe imple-

mentation of thrombolysis in stroke-monitoring study

(SITS-MOST): an observational study. Lancet 2007;

369: 275–282.

34. von Kummer R, Broderick JP, Campbell BC, et al. The

Heidelberg Bleeding Classification: classification of

bleeding events after ischemic stroke and reperfusion

therapy. Stroke 2015; 46: 2981–2986.

35. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ

and van Gijn J. Interobserver agreement for the assess-

ment of handicap in stroke patients. Stroke 1988; 19:

604–607.

36. Casaubon LK, Boulanger JM, Blacquiere D, et al.

Canadian stroke best practice recommendations: hyper-

acute stroke care guidelines, update 2015. Int J Stroke

2015; 10: 924–940.

37. Campbell BC, Donnan GA, Lees KR, et al.

Endovascular stent thrombectomy: the new standard of

care for large vessel ischaemic stroke. Lancet Neurol 2015;

14: 846–854.

38. Coutts SB, Modi J, Patel SK, et al. CT/CT angiography

and MRI findings predict recurrent stroke after transient

ischemic attack and minor stroke: results of the prospect-

ive CATCH study. Stroke 2012; 43: 1013–1017.

39. Furlan A, Higashida R, Wechsler L, et al. Intra-arterial

prourokinase for acute ischemic stroke. The PROACT II

International Journal of Stroke, 0(0)

Sacks et al. 17

study: a randomized controlled trial. Prolyse in acute

cerebral thromboembolism. JAMA 1999; 282: 2003–2011.

40. Penumbra Pivotal Stroke Trial I. The penumbra pivotal

stroke trial: safety and effectiveness of a new generation

of mechanical devices for clot removal in intracranial

large vessel occlusive disease. Stroke 2009; 40: 2761–2768.

41. Smith WS, Sung G, Saver J, et al. Mechanical thrombec-

tomy for acute ischemic stroke: final results of the Multi

MERCI trial. Stroke 2008; 39: 1205–1212.

42. Tarr R, Hsu D, Kulcsar Z, et al. The POST trial: initial

post-market experience of the Penumbra system: revascu-

larization of large vessel occlusion in acute ischemic

stroke in the United States and Europe. J Neurointerv

Surg 2010; 2: 341–344.

43. Fransen PS, Berkhemer OA, Lingsma HF, et al. Time to

reperfusion and treatment effect for acute ischemic

stroke: a randomized clinical trial. JAMA Neurol 2016;

73: 190–196.

44. Goyal M, Jadhav AP, Bonafe A, et al. Analysis of work-

flow and time to treatment and the effects on outcome in

endovascular treatment of acute ischemic stroke: results

from the SWIFT PRIME randomized controlled trial.

Radiology 2016; 279: 888–897.

45. Khatri P, Abruzzo T, Yeatts SD, et al. Good clinical

outcome after ischemic stroke with successful revascular-

ization is time-dependent. Neurology 2009; 73:

1066–1072.

46. Saver JL, Goyal M, van der Lugt A, et al. Time to treat-

ment with endovascular thrombectomy and outcomes

from ischemic stroke: a meta-analysis. JAMA 2016;

316: 1279–1288.

47. Lansberg MG, Cereda CW, Mlynash M, et al. Response

to endovascular reperfusion is not time-dependent in

patients with salvageable tissue. Neurology 2015; 85:

708–714.

48. Nogueira R and Jovin T. Clinical mismatch in the triage

of wake up and late presenting strokes undergoing neu-

rointervention with trevo (DAWN). N Engl J Med 2018;

378: 11–21.

49. POSITIVE stroke clinical trial. Available at: https://clin-

icaltrials.gov/ct2/show/NCT01852201?term¼posi-

tiveþstrokeþtrial&rank¼1. Accessed February 12, 2016.

50. Endovascular therapy following imaging evaluation

for ischemic stroke 3 (DEFUSE 3). Available at:

https://clinicaltrials.gov/ct2/show/NCT02586415.

Accessed February 12, 2016.

51. Brandt T, von Kummer R, Muller-Kuppers M and

Hacke W. Thrombolytic therapy of acute basilar artery

occlusion. Variables affecting recanalization and out-

come. Stroke 1996; 27: 875–881.

52. Lin DD, Gailloud P, Beauchamp NJ, Aldrich EM, Wityk

RJ and Murphy KJ. Combined stent placement and

thrombolysis in acute vertebrobasilar ischemic stroke.

AJNR Am J Neuroradiol 2003; 24: 1827–1833.

53. Schonewille WJ, Wijman CA, Michel P, et al. Treatment

and outcomes of acute basilar artery occlusion in the

basilar artery international cooperation study

(BASICS): a prospective registry study. Lancet Neurol

2009; 8: 724–730.

54. Basilar artery international cooperation study (BASICS).

Available at: https://clinicaltrials.gov/ct2/show/NCT017

17755?term¼basicsþstrokeþtrial&rank¼1. Accessed

April 11, 2017.

55. Basilar artery occlusion Chinese endovascular trial.

Available at: https://clinicaltrials.gov/ct2/show/NCT027

37189?term¼bestþstrokeþtrial&rank¼2. Accessed April

11, 2017.

56. Hacke W, Kaste M, Fieschi C, et al. Randomised double-

blind placebo-controlled trial of thrombolytic therapy

with intravenous alteplase in acute ischaemic stroke

(ECASS II). Second European-Australasian Acute

Stroke Study Investigators. Lancet 1998; 352: 1245–1251.

57. Barber PA, Demchuk AM, Zhang J and Buchan AM.

Validity and reliability of a quantitative computed tom-

ography score in predicting outcome of hyperacute stroke

before thrombolytic therapy. ASPECTS Study Group.

Alberta Stroke Programme early CT score. Lancet

2000; 355: 1670–1674.

58. Pexman JH, Barber PA, Hill MD, et al. Use of the

Alberta Stroke Program early CT score (ASPECTS) for

assessing CT scans in patients with acute stroke. AJNR

Am J Neuroradiol 2001; 22: 1534–1542.

59. Efficacy and safety of thrombectomy in stroke with

extended lesion and extended time window (tension).

Available at: https://clinicaltrials.gov/show/

NCT03094715. Accessed April 11, 2017.

60. Riedel CH, Zoubie J, Ulmer S, Gierthmuehlen J and

Jansen O. Thin-slice reconstructions of nonenhanced

CT images allow for detection of thrombus in acute

stroke. Stroke 2012; 43: 2319–2323.

61. Riedel CH, Zimmermann P, Jensen-Kondering U,

Stingele R, Deuschl G and Jansen O. The importance

of size: successful recanalization by intravenous thromb-

olysis in acute anterior stroke depends on thrombus

length. Stroke 2011; 42: 1775–1777.

62. Rohan V, Baxa J, Tupy R, et al. Length of occlusion

predicts recanalization and outcome after intravenous

thrombolysis in middle cerebral artery stroke. Stroke

2014; 45: 2010–2017.

63. Ahn SH, d’Esterre CD, Qazi EM, et al. Occult antero-

grade flow is an under-recognized but crucial predictor of

early recanalization with intravenous tissue-type plas-

minogen activator. Stroke 2015; 46: 968–975.

64. Menon BK, d’Esterre CD, Qazi EM, et al. Multiphase

CT angiography: a new tool for the imaging triage of

patients with acute ischemic stroke. Radiology 2015;

275: 510–520.

65. Gilgen MD, Klimek D, Liesirova KT, et al. Younger

stroke patients with large pretreatment diffusion-

weighted imaging lesions may benefit from endovascular

treatment. Stroke 2015; 46: 2510–2516.

66. Borst J, Berkhemer OA, Roos YB, et al. Value of com-

puted tomographic perfusion-based patient selection for

intra-arterial acute ischemic stroke treatment. Stroke

2015; 46: 3375–3382.

67. d’Esterre CD, Boesen ME, Ahn SH, et al. Time-depen-

dent computed tomographic perfusion thresholds for

patients with acute ischemic stroke. Stroke 2015; 46:

3390–3397.

International Journal of Stroke, 0(0)

18 International Journal of Stroke 0(0)

68. Barreto AD, Albright KC, Hallevi H, et al. Thrombus

burden is associated with clinical outcome after intra-

arterial therapy for acute ischemic stroke. Stroke 2008;

39: 3231–3235.

69. Lin R, Vora N, Zaidi S, et al. Mechanical approaches

combined with intra-arterial pharmacological therapy

are associated with higher recanalization rates than

either intervention alone in revascularization of acute car-

otid terminus occlusion. Stroke 2009; 40: 2092–2097.

70. Shi ZS, Loh Y, Walker G and Duckwiler GR; MERCI

and Multi-MERCI Investigators. Clinical outcomes in

middle cerebral artery trunk occlusions versus secondary

division occlusions after mechanical thrombectomy:

pooled analysis of the mechanical embolus removal in

cerebral ischemia (MERCI) and multi MERCI trials.

Stroke 2010; 41: 953–960.

71. Coutinho JM, Liebeskind DS, Slater LA, et al.

Mechanical thrombectomy for isolated M2 occlusions: a

post hoc analysis of the STAR, SWIFT, and SWIFT

PRIME studies. AJNR Am J Neuroradiol 2016; 37:

667–672.

72. Busl KM, Nogueira RG, Yoo AJ, Hirsch JA, Schwamm

LH and Rost NS. Prestroke dementia is associated with

poor outcomes after reperfusion therapy among elderly

stroke patients. J Stroke Cerebrovasc Dis 2013; 22:

718–724.

73. Khatri P, Hill MD, Palesch YY, et al. Methodology of

the Interventional Management of Stroke III Trial. Int J

Stroke 2008; 3: 130–137.

74. Bhole R, Goyal N, Nearing K, et al. Implications of

limiting mechanical thrombectomy to patients with emer-

gent large vessel occlusion meeting top tier evidence cri-

teria. J Neurointerv Surg 2017; 9: 225–228.

75. Goyal N, Tsivgoulis G, Frei D, et al. A multicenter study

of the safety and effectiveness of mechanical thrombec-

tomy for patients with acute ischemic stroke not meeting

top-tier evidence criteria. J Neurointerv Surg 2018; 10:

10–16.

76. Leifer D, Bravata DM, Connors JJ III, et al. Metrics for

measuring quality of care in comprehensive stroke cen-

ters: detailed follow-up to Brain Attack Coalition com-

prehensive stroke center recommendations: a statement

for healthcare professionals from the American Heart

Association/American Stroke Association. Stroke 2011;

42: 849–877.

77. Saver JL and Gornbein J. Treatment effects for which

shift or binary analyses are advantageous in acute

stroke trials. Neurology 2009; 72: 1310–1315.

78. Interventional stroke therapy outcomes registry

(INSTOR). Available at: http://www.strokeregistry.org.

Accessed July 19, 2016.

79. Meyers PM, Schumacher HC, Alexander MJ, et al.

Performance and training standards for endovascular

ischemic stroke treatment. J Stroke Cerebrovasc Dis

2009; 18: 411–415.

80. Schwamm LH, Fonarow GC, Reeves MJ, et al. Get with

the guidelines—stroke is associated with sustained

improvement in care for patients hospitalized with acute

stroke or transient ischemic attack. Circulation 2009; 119:

107–115.

81. SITS–thrombectomy registry. Available at: http://www.

sitsinternational.org/registries/sits-thrombectomy/.

Accessed August 12, 2016.

82. MR CLEAN registry. Available at: http://www.mrclean-

trial.org.

83. Menon BK, Saver JL, Goyal M, et al. Trends in endo-

vascular therapy and clinical outcomes within the nation-

wide get with the guidelines–stroke registry. Stroke 2015;

46: 989–995.

84. Hacke W, Donnan G, Fieschi C, et al. Association of

outcome with early stroke treatment: pooled analysis of

ATLANTIS, ECASS, and NINDS rt-PA stroke trials.

Lancet 2004; 363: 768–774.

85. Lansberg MG, Schrooten M, Bluhmki E, Thijs VN and

Saver JL. Treatment time-specific number needed to treat

estimates for tissue plasminogen activator therapy in

acute stroke based on shifts over the entire range of the

modified Rankin scale. Stroke 2009; 40: 2079–2084.

86. Menon BK, Sajobi TT, Zhang Y, et al. Analysis of work-

flow and time to treatment on thrombectomy outcome in

the endovascular treatment for small core and proximal

occlusion ischemic stroke (ESCAPE) randomized, con-

trolled trial. Circulation 2016; 133: 2279–2286.

87. Ribo M, Molina CA, Cobo E, et al. Association between

time to reperfusion and outcome is primarily driven by

the time from imaging to reperfusion. Stroke 2016; 47:

999–1004.

88. Bradley EH, Curry LA, Webster TR, et al. Achieving

rapid door-to-balloon times: how top hospitals improve

complex clinical systems. Circulation 2006; 113:

1079–1085.

89. Krumholz HM, Bradley EH, Nallamothu BK, et al. A

campaign to improve the timeliness of primary percutan-

eous coronary intervention: door-to-balloon: an alliance

for quality. JACC Cardiovasc Interv 2008; 1: 97–104.

90. Fonarow GC, Smith EE, Saver JL, et al. Improving door-

to-needle times in acute ischemic stroke: the design and

rationale for the American Heart Association/American

Stroke Association’s target: stroke initiative. Stroke 2011;

42: 2983–2989.

91. Mitka M. Reducing door-to-needle time for tPA use

remains an elusive goal in stroke care. JAMA 2011;

305: 1288–1289.

92. Meretoja A, Strbian D, Mustanoja S, Tatlisumak T,

Lindsberg PJ and Kaste M. Reducing in-hospital delay

to 20 minutes in stroke thrombolysis. Neurology 2012; 79:

306–313.

93. Rai AT, Smith MS, Boo S, Tarabishy AR, Hobbs GR

and Carpenter JS. The ‘pit-crew’ model for improving

door-to-needle times in endovascular stroke therapy: a

Six-Sigma project. J Neurointerv Surg 2016; 8: 447–452.

94. Costalat V, Machi P, Lobotesis K, et al. Rescue, com-

bined, and stand-alone thrombectomy in the manage-

ment of large vessel occlusion stroke using the solitaire

device: a prospective 50-patient single-center study:

timing, safety, and efficacy. Stroke 2011; 42: 1929–1935.

95. Miley JT, Memon MZ, Hussein HM, et al. A multicenter

analysis of ‘‘time to microcatheter’’ for endovascular

therapy in acute ischemic stroke. J Neuroimaging 2011;

21: 159–164.

International Journal of Stroke, 0(0)

Sacks et al. 19

96. Sun CH, Ribo M, Goyal M, et al. Door-to-puncture: a

practical metric for capturing and enhancing system

processes associated with endovascular stroke care, pre-

liminary results from the rapid reperfusion registry.

J Am Heart Assoc 2014; 3: e000859.

97. Zaidat OO, Castonguay AC, Gupta R, et al. North

American solitaire stent retriever acute stroke registry:

post-marketing revascularization and clinical outcome

results. J Neurointerv Surg 2014; 6: 584–588.

98. Nogueira RG, Lutsep HL, Gupta R, et al. Trevo versus

Merci retrievers for thrombectomy revascularisation of

large vessel occlusions in acute ischaemic stroke

(TREVO 2): a randomised trial. Lancet 2012; 380:

1231–1240.

99. Saver JL, Jahan R, Levy EI, et al. Solitaire flow restor-

ation device versus the Merci Retriever in patients with

acute ischaemic stroke (SWIFT): a randomised, parallel-

group, non-inferiority trial. Lancet 2012; 380:

1241–1249.

100. Abilleira S, Ribera A, Davalos A, et al. Functional out-

come after primary endovascular therapy or IV thromb-

olysis alone for stroke. An observational, comparative

effectiveness study. Cerebrovasc Dis 2014; 38: 328–336.

101. Goyal M, Almekhlafi MA, Fan L, et al. Evaluation of

interval times from onset to reperfusion in patients

undergoing endovascular therapy in the interventional

management of stroke III trial. Circulation 2014; 130:

265–272.

102. van Heerden J, Yan B, Churilov L, Dowling RJ and

Mitchell PJ. Picture-to-puncture time in acute stroke

endovascular intervention: are we getting faster?

J Neurointerv Surg 2015; 7: 564–568.

103. Nikoubashman O, Probst T, Schurmann K, et al.

Weekend effect in endovascular stroke treatment: do

treatment decisions, procedural times, and outcome

depend on time of admission? J Neurointerv Surg

2017; 9: 336–339.

104. Latchaw RE, Alberts MJ, Lev MH, et al.

Recommendations for imaging of acute ischemic

stroke: a scientific statement from the American Heart

Association. Stroke 2009; 40: 3646–3678.

105. McTaggart RA, Ansari SA, Goyal M, et al. Initial hos-

pital management of patients with emergent large vessel

occlusion (ELVO): report of the standards and guide-

lines committee of the Society of NeuroInterventional

Surgery. J Neurointerv Surg 2017; 9: 316–323.

106. Cho TH, Nighoghossian N, Mikkelsen IK, et al.

Reperfusion within 6 hours outperforms recanalization

in predicting penumbra salvage, lesion growth, final

infarct, and clinical outcome. Stroke 2015; 46:

1582–1589.

107. Struffert T, Deuerling-Zheng Y, Engelhorn T, et al.

Feasibility of cerebral blood volume mapping by flat

panel detector CT in the angiography suite: first experi-

ence in patients with acute middle cerebral artery occlu-

sions. AJNR Am J Neuroradiol 2012; 33: 618–625.

108. Higashida RT, Furlan AJ, Roberts H, et al. Trial design

and reporting standards for intra-arterial cerebral

thrombolysis for acute ischemic stroke. Stroke 2003;

34: e109–e137.

109. The Thrombolysis in Myocardial Infarction (TIMI)

trial. Phase I findings. TIMI Study Group. N Engl J

Med 1985; 312: 932–936.

110. Chesebro JH, Knatterud G, Roberts R, et al.

Thrombolysis in myocardial infarction (TIMI) Trial,

phase I: a comparison between intravenous tissue plas-

minogen activator and intravenous streptokinase.

Clinical findings through hospital discharge.

Circulation 1987; 76: 142–154.

111. Mori E, Yoneda Y, Tabuchi M, et al. Intravenous

recombinant tissue plasminogen activator in acute car-

otid artery territory stroke. Neurology 1992; 42:

976–982.

112. Qureshi AI. New grading system for angiographic evalu-

ation of arterial occlusions and recanalization response

to intra-arterial thrombolysis in acute ischemic stroke.

Neurosurgery 2002; 50: 1405–1414.

113. Khatri P, Neff J, Broderick JP, et al. Revascularization

end points in stroke interventional trials: recanalization

versus reperfusion in IMS-I. Stroke 2005; 36: 2400–2403.

114. Gerber JC, Miaux YJ and von Kummer R. Scoring flow

restoration in cerebral angiograms after endovascular

revascularization in acute ischemic stroke patients.

Neuroradiology 2015; 57: 227–240.

115. Zaidat OO, Lazzaro MA, Liebeskind DS, et al.

Revascularization grading in endovascular acute ische-

mic stroke therapy. Neurology 2012; 79(suppl 1):

S110–S116.

116. Almekhlafi MA, Mishra S, Desai JA, et al. Not all ‘‘suc-

cessful’’ angiographic reperfusion patients are an equal

validation of a modified TICI scoring system. Interv

Neuroradiol 2014; 20: 21–27.

117. Kleine JF, Wunderlich S, Zimmer C and Kaesmacher J.

Time to redefine success? TICI 3 versus TICI 2b reca-

nalization in middle cerebral artery occlusion treated

with thrombectomy. J Neurointerv Surg 2017; 9:

117–121.

118. Abilleira S, Cardona P, Ribo M, et al. Outcomes of a

contemporary cohort of 536 consecutive patients with

acute ischemic stroke treated with endovascular therapy.

Stroke 2014; 45: 1046–1052.

119. Gratz PP, Jung S, Schroth G, et al. Outcome of stand-

ard and high-risk patients with acute anterior circulation

stroke after stent retriever thrombectomy. Stroke 2014;

45: 152–158.

120. Gaha M, Roy C, Estrade L, et al. Inter- and intraobser-

ver agreement in scoring angiographic results of intra-

arterial stroke therapy. AJNR Am J Neuroradiol 2014;

35: 1163–1169.

121. Fiehler J, Cognard C, Gallitelli M, et al. European rec-

ommendations on organisation of interventional care in

acute stroke (EROICAS). Int J Stroke 2016; 11:

701–716.

122. Ogawa A, Mori E, Minematsu K, et al. Randomized

trial of intraarterial infusion of urokinase within 6

hours of middle cerebral artery stroke: the middle cere-

bral artery embolism local fibrinolytic intervention trial

(MELT) Japan. Stroke 2007; 38: 2633–2639.

123. Yoon W, Jung MY, Jung SH, Park MS, Kim JT and

Kang HK. Subarachnoid hemorrhage in a multimodal

International Journal of Stroke, 0(0)

20 International Journal of Stroke 0(0)

approach heavily weighted toward mechanical thromb-

ectomy with solitaire stent in acute stroke. Stroke 2013;

44: 414–419.

124. Herial N, Qureshi M, Khan A, et al. Arterial reocclusion

and distal embolization during endovascular treatment

using new generation stent retrievers in acute ischemic

stroke patients (P4.299). Neurology 2015; 84(14 suppl

P4): 299.

125. Janjua N, Alkawi A, Suri MF and Qureshi AI. Impact

of arterial reocclusion and distal fragmentation during

thrombolysis among patients with acute ischemic stroke.

AJNR Am J Neuroradiol 2008; 29: 253–8.

126. Kerr DM, Fulton RL and Lees KR; VISTA

Collaborators. Seven-day NIHSS is a sensitive outcome

measure for exploratory clinical trials in acute stroke:

evidence from the Virtual International Stroke Trials

Archive. Stroke 2012; 43: 1401–1403.

127. Sajobi TT, Menon BK, Wang M, et al. Early trajectory

of stroke severity predicts long-term functional out-

comes in ischemic stroke subjects: results from the

ESCAPE trial (endovascular treatment for small core

and anterior circulation proximal occlusion with empha-

sis on minimizing CT to recanalization times). Stroke

2017; 48: 105–110.

128. Janssen PM, Visser NA, Dorhout Mees SM, Klijn CJ,

Algra A and Rinkel GJ. Comparison of telephone and

face-to-face assessment of the modified Rankin scale.

Cerebrovasc Dis 2010; 29: 137–139.

129. Muir KW, Ford GA, Messow CM, et al. Endovascular

therapy for acute ischaemic stroke: the pragmatic

ischaemic stroke thrombectomy evaluation (PISTE)

randomised, controlled trial. J Neurol Neurosurg

Psychiatry 2017; 88: 38–44.

130. Khan M, Goddeau RP Jr, Zhang J, Moonis M and

Henninger N. Predictors of outcome following stroke

due to isolated M2 occlusions. Cerebrovasc Dis Extra

2014; 4: 52–60.

131. Alonso de Lecinana M, Kawiorski MM, Ximenez-

Carrillo A, et al. Mechanical thrombectomy for basilar

artery thrombosis: a comparison of outcomes with

anterior circulation occlusions. J Neurointerv Surg

2017; 60: 635–643.

132. Minnerup J, Wersching H, Teuber A, et al. Outcome

after thrombectomy and intravenous thrombolysis in

patients with acute ischemic stroke: a prospective obser-

vational study. Stroke 2016; 47: 1584–1592.

133. Nogueira RG, Zaidat OO, Castonguay AC, et al.

Rescue thrombectomy in large vessel occlusion strokes

leads to better outcomes than intravenous thrombolysis

alone: a ‘real world’ applicability of the recent trials.

Interv Neurol 2016; 5: 101–110.

134. Jansen I, Mulder M, Goldhoorn RJ, et al; on behalf of

the MRCLEAN-Registry investigators (www.mrclean-

trial.org). MR CLEAN registry: a post-trial multicenter

registry of intra-arterial treatment for acute ischemic

stroke in The Netherlands. Presented at the

International Stroke Conference; February 21–24,

2017; Houston, TX.

135. Direct transfer to an endovascular center compared to

transfer to the closest stroke center in acute stroke

patients with suspected large vessel occlusion

(RACECAT). Available at: https://clinicaltrials.gov/

ct2/show/NCT02795962. Accessed April 11, 2017.

136. Legal Protections for Peer Review H-375.962: American

Medical Association; Available at: https://searchpf.ama-

assn.org/SearchML/searchDetails.action?uri¼%

2FAMADoc%2FHOD.xml-0-3167.xml. Accessed May

31, 2012.

137. The Health Care Quality Improvement Act of 1986

(HCQIA), 42 USC §11101 et seq.

138. Suydam S, Liang BA, Anderson S, Weinger MB. Patient

safety data sharing and protection from legal discovery.

In: Henriksen K, Battles JB, Marks ES, Lewin DI, edi-

tors. Advances in Patient Safety: From Research to

Implementation.Volume 3: Implementation Issues.

Advances in Patient Safety. Rockville, MD: Agency for

Healthcare Research and Quality, 2005. Available at:

https://www.ncbi.nlm.nih.gov/books/NBK20558/.

Accessed January 20, 2018.

139. Willner RB. Health Care Quality Improvement Act

(HCQIA) of 1986. What is it? Why was it established?

Is it working? Available at: http://www.peerreview.org/

articles/HCQIQ.htm. Accessed May 31, 2012.

140. H.R. 2—114th Congress: Medicare Access and CHIP

Reauthorization Act of 2015. Available at: http://

www.congress.gov/bill/114th-congress/house-bill/2.

Accessed April 24, 2017.

141. Hirsch JA, Harvey HB, Barr RM, et al. Sustainable

growth rate repealed, MACRA revealed: historical con-

text and analysis of recent changes in Medicare phys-

ician payment methodologies. AJNR Am J Neuroradiol

2016; 37: 210–214.

142. Hirsch JA, Leslie-Mazwi TM, Patel AB, et al. MACRA:

background, opportunities and challenges for the neu-

rointerventional specialist. J Neurointerv Surg 2016; 8:

868–874.

143. Berkhemer OA, Jansen IG, Beumer D, et al. Collateral

status on baseline computed tomographic angiography

and intra-arterial treatment effect in patients with prox-

imal anterior circulation stroke. Stroke 2016; 47:

768–776.

144. Hussein HM, Georgiadis AL, Vazquez G, et al.

Occurrence and predictors of futile recanalization fol-

lowing endovascular treatment among patients with

acute ischemic stroke: a multicenter study. AJNR Am

J Neuroradiol 2010; 31: 454–458.

145. Kim JT, Jahan R and Saver JL.; SWIFT Investigators.

Impact of glucose on outcomes in patients treated with

mechanical thrombectomy: a post hoc analysis of the

solitaire flow restoration with the intention for thromb-

ectomy study. Stroke 2016; 47: 120–127.

146. Institute of Medicine (US) Committee on Quality of

Health Care in America; Kohn LT, Corrigan JM,

Donaldson MS, editors. To Err is Human: Building a

Safer Health System. Washington DC: National

Academies Press, 2000.

International Journal of Stroke, 0(0)

Sacks et al. 21

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Jun 2024

BACKGROUND Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) has been a longstanding challenge. The prognosis of patients with PDAC depends on the stage at diagnosis. It is necessary to identify biomarkers for the detection and differentiation of pancreatic tumors and optimize PDAC sample preparation procedures for DNA and RNA analysis. Most molecular studies are done using paraffin-embedded blocks; however, the integrity of DNA and RNA is often compromised in this format. Moreover, RNA isolated from human pancreatic tissue samples is generally of low quality, in part, because of the high concentration of endogenous pancreatic RNAse activity present. AIM To assess the potential of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to obtain specimens from pancreatic neoplasms for subsequent RNA molecular profiling, including next-generation sequencing (NGS). METHODS Thirty-four EUS-FNA samples were included in this study: PDAC (n = 15), chronic pancreatitis (n = 5), pancreatic cysts (n = 14), mucinous cysts (mucinous cystic neoplasia/intraductal papillary mucinous neoplasia) n = 7, serous cystic neoplasms n = 5, and pseudocysts n = 2. Cyst material consisted of cyst fluid and cyst wall samples obtained by through-the-needle biopsy (TTNB). Samples were stored at -80 °C until analysis. RNA purity (A260/230, A260/280 ratios), concentration, and integrity (RIN) were assessed. Real-time polymerase chain reaction was conducted on all samples, and small RNA libraries were prepared from solid mass samples. RESULTS RNA was successfully extracted from 29/34 (85%) EUS-FNA samples: 100% pancreatic adenocarcinoma samples, 100% chronic pancreatitis samples, 70% pancreatic fluid cyst samples, and 50% TTNB samples. The relative expression of GAPDH and HPRT were obtained for all successfully extracted RNA samples (n = 29) including low-quality RNA specimens. Low concentration and nonoptimal RIN values (no less than 3) of RNA extracted from EUS-FNA samples did not prevent NGS library preparation. The suitability of cyst fluid samples for RNA profiling varied. The quality of RNA extracted from mucinous cyst fluid had a median RIN of 7.7 (5.0-8.2), which was compatible with that from solid neoplasms [6.2 (0-7.8)], whereas the quality of the RNA extracted from all fluids of serous cystic neoplasms and TTNB samples had a RIN of 0. CONCLUSION The results demonstrate the high potential of EUS-FNA material for RNA profiling of various pancreatic lesions, including low-quality RNA specimens.

Anti-PD-1 cancer immunotherapy induces central nervous system immune-related adverse events by microglia activation

Article

Jun 2024
Sci Transl Med

Cancer treatment with anti–PD-1 immunotherapy can cause central nervous system immune-related adverse events (CNS-irAEs). The role of microglia in anti–PD-1 immunotherapy–induced CNS-irAEs is unclear. We found that anti–PD-1 treatment of mice caused morphological signs of activation and major histocompatibility complex (MHC) class II up-regulation on microglia. Functionally, anti–PD-1 treatment induced neurocognitive deficits in mice, independent of T cells, B cells, and natural killer cells. Instead, we found that microglia mediated these CNS-irAEs. Single-cell RNA sequencing revealed major transcriptional changes in microglia upon anti–PD-1 treatment. The anti–PD-1 effects were mediated by anti–PD-1 antibodies interacting directly with microglia and were not secondary to peripheral T cell activation. Using a proteomics approach, we identified spleen tyrosine kinase (Syk) as a potential target in activated microglia upon anti–PD-1 treatment. Syk inhibition reduced microglia activation and improved neurocognitive function without impairing anti-melanoma effects. Moreover, we analyzed CNS tissue from a patient cohort that had received anti–PD-1 treatment. Imaging mass cytometry revealed that anti–PD-1 treatment of patients was associated with increased surface marker expression indicative of microglia activation. In summary, we identified a disease-promoting role for microglia in CNS-irAEs driven by Syk and provide an inhibitor-based approach to interfere with this complication after anti–PD-1 immunotherapy.

A randomized controlled trial to test efficacy and safety of thrombectomy in stroke with extended lesion and extended time window

Article

Full-text available

Aug 2018

Rationale: The benefit of thrombectomy in patients with intracranial large vessel occlusion of the anterior circulation has been shown in selected patients in previous randomized controlled trials, but patients with extended ischemic lesions were excluded in the majority of these trials. TENSION aims to demonstrate efficacy and safety of thrombectomy in patients with extended lesions in an extended time window (up to 12 h from onset or from last seen well). Design: TENSION is an investigator-initiated, randomized controlled, open label, blinded endpoint, European, two-arm, postmarket study to compare the safety and effectiveness of thrombectomy as compared to best medical care alone in stroke patients with extended stroke lesions defined by an Alberta Stroke Program Early Computed Tomography Scan score of 3-5 and in an extended time window. In an adaptive design study, up to 665 patients will be randomized. Outcomes: Primary efficacy endpoint will be clinical outcome defined by the modified Rankin Scale at 90-day poststroke. The main safety endpoint will be death and dependency (modified Rankin Scale 4-6) at 90 days. Additional effect measures include adverse events, health-related quality of life, poststroke depression, and costs utility assessment. Discussion: TENSION may make effective treatment available for patients with severe stroke in an extended time window, thereby improving functional outcome and quality of life of thousands of stroke patients and reducing the individual, societal, and economic burden of death and disability resulting from severe stroke. TENSION is registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier NCT03094715).

Standards for providing safe acute ischaemic stroke thrombectomy services (September 2015)

Article

Full-text available

Dec 2016

Heart disease and stroke statistics-2015 update: a report from the American Heart Association

Article

Full-text available

Jan 2015
CIRCULATION

Abstract T MP10: Arterial Reocclusion And Distal Embolization During Endovascular Treatment Using New Generation Stent Retrievers In Acute Ischemic Stroke Patients

Article

Feb 2015

BACKGROUND AND PURPOSE: Arterial reocclusion and distal embolization have been identified in previous studies of endovascular treatment in patients with acute ischemic stroke. We determined the rates of reocclusion and distal embolization during endovascular treatment using new generation stent retrievers. MATERIALS AND METHODS: Acute ischemic stroke patients underwent mechanical thrombectomy using new generation stent retrievers without intra-procedural heparin or proximal flow arrest for angiographically demonstrated arterial occlusion. "Distal embolization" was defined qualitatively as appearance of an occlusion on a downstream vessel. "Arterial reocclusion" was defined as subsequent reocclusion of the target vessel after initial recanalization had been achieved. The rates were compared with data from 4 previous prospective acute stroke protocols prior to availability of stent retrievers. RESULTS: The median initial National Institutes of Health Scale Score (NIHSS) for these patients was 14 (range 34-0); mean time from symptom onset to treatment was 5.2 +/- 2.6 hr. Arterial reocclusion occurred in 2.3% of these patients, whereas distal embolization occurred in 24% of the 86 patients. The rates of arterial reocclusion (3.0% versus 1.9%) and distal fragmentation (21.2% versus 30.8%) were similar in patients who did or did not receive IV alteplase prior to thrombectomy. Arterial reocclusion, but not distal embolization, was associated with a lower likelihood of favorable outcome at 1-3 months (P = .05; odds ratio, 3.9; 95% confidence interval, 0.01-0.98) after adjusting for age, initial NIHSS, sex, time to treatment, initial angiographic grade, symptomatic intracranial hemorrhage, and final recanalization. The rates of arterial reocclusion (2.1% versus 2.6% of 86 patients, p=0.8) and distal embolization (35.4% versus 18.4% of 86 patients, p=0.8) were not similar in patients treated with and without stent retrievers. CONCLUSIONS: Arterial reocclusion and distal embolization occur in 16%-18% of acute ischemic stroke patients undergoing mechanical thrombectomy with new stent retrievers without IV heparin or proximal flow arrest. The rates are no higher than those observed in cohorts treated without stent retrievers.

Abstract 35: MR CLEAN Registry: A Post-trial Multicenter Registry of Intra-arterial Treatment for Acute Ischemic Stroke in the Netherlands

Article

Feb 2017

Background & Purpose: Intra-arterial therapy (IAT) is being implemented worldwide as the main treatment option for acute ischemic stroke (AIS). We wondered whether effectiveness and safety results that have been reported in randomized clinical trials can be reproduced in everyday clinical practice. We will report results of the Dutch National post MR CLEAN IAT registry including work flow parameters, primary and secondary outcomes, as well as serious adverse events. Methods: The MR CLEAN Registry is a prospective registry of all patients undergoing IAT for AIS in the Netherlands, started after completion of the MR CLEAN trial in March 2014. Registration was required for reimbursement. A core set was defined, with inclusion criteria similar to those of the MR CLEAN trial, including a proven anterior circulation occlusion and treatment possible withing 6 hours from onset. The primary study outcome is the score on the modified Rankin Scale (mRS) at 90 days. The secondary clinical outcome is NIHSS after 24 to 48 hours. Secondary radiological outcomes include the mTICI score on DSA and final infarct volume and major bleeding on follow up NCCT. We used a propensity weighted and an unadjusted ordinal logistic regression model to compare outcomes in the MR CLEAN Registry core and total dataset with the treatment arm of MR CLEAN. Results: Between March 2014 and August 2016 the inclusion rate of the MR CLEAN Registry has been increasing steadily to an average of 79 (SD 22) per month for a cumulative inclusion of 1548 patients in July 2016 (Figure 1). Conclusions: The MR CLEAN registry data is now being analyzed. Results will be reported at the conference.

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct

Article

Nov 2017

Background The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. Methods We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days. Results A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00). Conclusions Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283.)

A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3)

Article

Mar 2017

Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion. No randomized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset. Aim The aim of the study is to demonstrate that, among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging, endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke. Design The study is a prospective, randomized, multicenter, phase III, adaptive, blinded endpoint, controlled trial. A maximum of 476 patients will be randomized and treated between 6 and 16 h of symptom onset. Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion, and automated software (RAPID) determines if the Target Mismatch Profile is present. Patients who meet both clinical and imaging selection criteria are randomized 1:1 to endovascular therapy plus medical management or medical management alone. The individual endovascular therapist chooses the specific device (or devices) employed. Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90. The secondary endpoint is the proportion of patients with modified Rankin Scale 0–2 at day 90 (indicating functional independence). Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon–Mann–Whitney test (the generalized likelihood ratio test).

A multicenter study of the safety and effectiveness of mechanical thrombectomy for patients with acute ischemic stroke not meeting top-tier evidence criteria

Article

Jan 2017

Background: While mechanical thrombectomy (MT) has become the standard of care for patients with acute ischemic stroke (AIS) with emergent large-vessel occlusions (ELVO), recently published guidelines appropriately award top-tier evidence to the same selective criteria that were employed in completed clinical trials. We sought to evaluate the safety and effectiveness of MT in patients with AIS with ELVO who do not meet top-tier evidence criteria (TTEC). Methods: We conducted an observational study on consecutive patients with AIS with ELVO who underwent MT at six high-volume endovascular centers. Standard safety outcomes (3-month mortality, symptomatic intracranial hemorrhage) and effectiveness outcomes (3-month functional independence: modified Rankin Scale scores of 0-2) were compared between patients meeting and failing TTEC. Results: The sample consisted of 349 (60%) controls fulfilling TTEC and 234 (40%) non-TTEC patients. Control patients meeting TTEC for MT tended to have higher functional independence rates at 3 months (47% vs 39%; p=0.055), while the rates of symptomatic intracerebral hemorrhage (sICH) were similar (9%) in both groups (p=0.983). In multivariable logistic regression models, adherence to TTEC for MT was not independently related to any safety outcome (sICH: OR 0.71, 95% CI 0.30 to 1.68, p=0.434; 3-month mortality: OR 1.27, 95% CI 0.69 to 2.33, p=0.448) or effectiveness outcome (3-month functional independence: OR 0.81, 95% CI 0.48 to 1.37, p=0.434; 3-month functional improvement: OR 0.73, 95% CI 0.48 to 1.11, p=0.138) after adjusting for potential confounders. Conclusions: Approximately 40% of patients with AIS with ELVO offered MT do not fulfill TTEC for MT. Patients who did not meet TTEC had high rates of good clinical outcome and low complication rates.

Mechanical thrombectomy for basilar artery thrombosis: A comparison of outcomes with anterior circulation occlusions

Article

Dec 2016
J Neurointerv Surg

Background and purpose: The benefits of mechanical thrombectomy (MT) in basilar artery occlusions (BAO) have not been explored in recent clinical trials. We compared outcomes and procedural complications of MT in BAO with anterior circulation occlusions. Methods: Data from the Madrid Stroke Network multicenter prospective registry were analyzed, including baseline characteristics, procedure times, procedural complications, symptomatic intracranial hemorrhage (SICH), modified Rankin Scale (mRS), and mortality at 3 months. Results: Of 479 patients treated with MT, 52 (11%) had BAO. The onset to reperfusion time lapse was longer in patients with BAO (median (IQR) 385 min (320-540) vs 315 min (240-415), p<0.001), as was the duration of the procedures (100 min (40-130) vs 60 min (39-90), p=0.006). Moreover, the recanalization rate was lower (75% vs 84%, p=0.01). A trend toward more procedural complications was observed in patients with BAO (32% vs 21%, p=0.075). The frequency of SICH was 2% vs 5% (p=0.25). At 3 months, patients with BAO had a lower rate of independence (mRS 0-2) (40% vs 58%, p=0.016) and higher mortality (33% vs 12%, p<0.001). The rate of futile recanalization was 50% in BAO versus 35% in anterior circulation occlusions (p=0.05). Age and duration of the procedure were significant predictors of futile recanalization in BAO. Conclusions: MT is more laborious and shows more procedural complications in BAO than in anterior circulation strokes. The likelihood of futile recanalization is higher in BAO and is associated with greater age and longer procedure duration. A refinement of endovascular procedures for BAO might help optimize the results.

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)

Article

Dec 2016

Background and purpose: The trajectory of neurological improvement after stroke treatment is clinically likely to be an important prognostic signal. We compared the accuracy of early longitudinal National Institutes of Health Stroke Scale (NIHSS) measurement versus other early markers of stroke severity post treatment in predicting subjects' 90-day stroke outcome. Methods: Data are from the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). Stroke severity was assessed at baseline, 1, 2, 5, 30, and 90 days. Subjects' functional outcome was assessed using the modified Rankin Scale at baseline, 30 days, and 90 days. Group-based trajectory model was used to identify distinct subgroups of longitudinal trajectories of NIHSS measured over the first 2, 5, and 30 days. The accuracy of baseline NIHSS, infarct volume, 24-hour change in NIHSS, infarct volume, and disease severity trajectory subgroups in predicting 90-day stroke outcome were assessed using logistic regression analysis. Results: Group-based trajectory model of the 2-day longitudinal NIHSS data revealed 3 distinct subgroups of NIHSS trajectories-large improvement (41.6%), minimal improvement (31.1%), and no improvement (27.3%) subgroups. Individuals in the large improvement group were more likely were more likely to exhibit good outcomes after 90 days than those in the minimal improvement or no improvement subgroup. Among candidate predictors, the 2-day trajectory subgroup variable was the most accurate in predicting 90-day modified Rankin Scale at 84.5%. Conclusions: Early trajectory of neurological improvement defined by 2-day longitudinal NIHSS data predicts functional outcomes with greater accuracy than other common variables. Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT01778335.