Emerging Therapy Critiques
Section Editors: Gustavo Saposnik, MD, and Daniel Strbian, MD, PhD
REVASCAT Trial
Further Advancement in Endovascular Stroke Therapy
Wade S. Smith, MD, PhD; Bernard Yan, MD
T he recent REVASCAT trial (Randomized Trial of
Revascularization With Solitaire FR Device Versus Best
Medical Therapy in the Treatment of Acute Stroke Due to
Anterior Circulation Large Vessel Occlusion Presenting
Within 8 Hours of Symptom Onset)1 is the latest of 5 published
Prospective Randomized Open Blinded End-Point (PROBE)-
designed trials of acute thrombectomy for acute, anterior cir-
Downloaded from http://stroke.ahajournals.org/ by guest on September 21, 2017
culation, large-vessel ischemic stroke serving to cap the era
of equipoise for endovascular stroke therapy.2–5 The history of
endovascular stroke therapy has recently been summarized.6
Following the null result of the Interventional Management
of Stroke (IMS)-III trial published in 2013,7 the field transi-
tioned to more effective removable stent (stentriever) device
design8,9 and use of imaging selection (principally computed
tomographic angiography with or without perfusion) rather
than clinical examination. The recent 5 trials were designed
around this evolution (a 6th trial has been stopped for efficacy
but not yet published10).
In the REVASCAT trial, investigators randomized acute
ischemic patients with large-vessel occlusion at 4 centers in
Catalonia, Spain. Eligible patients were aged between 18 and
80 years (later increased to 85 years), had computed tomo-
graphic angiography–defined occlusions of the carotid T or
M1 vessels, had baseline modified Rankin scale score ≤1, and
had minimum National Institutes of Health Stroke Scale score
≥5. The only significant exclusion criterion was the time to
endovascular treatment >8 hours and the absence of any sig-
nificant infarction (noncontrast computed tomography Alberta
Stroke Program Early CT Score [ASPECTS] <7 or diffusion-
weighted imaging ASPECTS <6). Patients in the treatment
arm could have been pretreated with intravenous tissue-type
plasminogen activator (IV tPA) but failed treatment by defi-
nition of persistent large-vessel occlusion on computed tomo-
graphic angiography. The control arm could be treated with
IV tPA, if eligible. Only 206 patients were randomized of 690
planned because the independent data safety and monitor-
ing board viewed the results of the preplanned 170 patients
who had 90-day outcome data and, although not significant,
recommended stopping the trial for ethical reasons in light of
the positive results of the Endovascular Treatment for Acute
Received July 14 2015, final revision received August 5, 2015; accepted August 6, 2015.
From the Department of Neurology, University of California San Francisco (W.S.S.); and Melbourne Brain Center, Royal Melbourne Hospital, University
of Melbourne, Melbourne, VIC, Australia (B.Y.).
Correspondence to Wade S. Smith, MD, PhD, Department of Neurology, University of California San Francisco, 505 Parnassus Ave, Room M-830, San
Francisco, CA 94143. E-mail smithw@neurology.ucsf.edu
(Stroke. 2015;46:3012-3013. DOI: 10.1161/STROKEAHA.115.010817.)
© 2015 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.115.010817
3012
Ischemic Stroke in the Netherlands (MR-CLEAN),2 Extending
the Time for Thrombolysis in Emergency Neurological
Deficits–Intra-Arterial (EXTEND-IA),3 and Endovascular
Treatment for Small Core and Proximal Occlusion Ischemic
Stroke (ESCAPE) trials.4 Subjects were well balanced in age,
baseline National Institutes of Health Stroke Scale, and time to
treatment because randomization was stratified by these vari-
ables. Only 7% of the thrombectomy patients underwent gen-
eral anesthesia (GA). At 90 days, the endovascular group fared
better than the control group (primary outcome odds ratio of
modified Rankin scale scores: 1.7 [1.05–2.8]); the prespecified
secondary outcome of favorable outcome (modified Rankin
scale ≤2) was found in 44% thrombectomy patients and in only
28% patients in the medical control arm. This resulted in an
adjusted odds ratio of 2.1 (95% confidence interval, 1.1–4.0),
and the number needed to treat to cause a favorable outcome of
6.4. Significantly notable was the analysis of a concurrent reg-
istry of stroke for the Catalonian region; only 8 patients during
the study who were eligible for the trial were not randomized.
The main conclusions of REVASCAT are as follows: (1)
the trials provide further support for the efficacy of endo-
vascular stroke therapy under 8 hours and (2) the results are
likely generalizable to the whole population. REVASCAT was
unique among the 5 published randomized controlled trials,
in which there was specific exclusion of patients who dem-
onstrated revascularization after IV tPA on neuroimaging.11
The protocol stipulated computed tomographic angiography
or magnetic resonance angiography at 30 minutes after IV tPA
for patients, specifically to identify the presence of revascular-
ization. The consequence was an inevitable delay in the initia-
tion of endovascular therapy as reflected in the increased time
delay between stroke onset to IV tPA time (median [interquar-
tile range], 117.5 [90–150] mins) and stroke onset to groin
puncture time (median [interquartile range], 269 [201–340]
mins) in the treatment group.1 REVASCAT did show, in spite
of treatment delay, superior clinical outcomes in the treat-
ment group, but this study did not measure whether this delay
was harmful. Of the 5 published PROBE-designed trials of
thrombectomy, only MR-CLEAN2 went onto planned com-
pletion, generating a domino effect where all other ongoing
 Smith and Yan   REVASCAT and Endovascular Therapy    3013
trials were terminated early for ethical reasons. The fact that
all 4 published subsequent trials, including REVASCAT, were
positive, despite not completing full enrollment, is strong
indication that endovascular stroke therapy within the 8-hour
time window is effective and trends toward reduced mortality.
Future meta-analysis of all PROBE-designed trials has been
planned,12 and REVASCAT will provide 206 precious obser-
vations to this analysis.
Regarding the generalizability of these results, it is sig-
nificant to consider that only 8 or 206 patients evaluated dur-
ing this trial in the 4 treating hospitals were not randomized.
We do not know, however, how centers with less experience
fare using these techniques because all 4 centers had to treat
over 500 stroke patients with at least 60 patients treated endo-
vascularly annually to be eligible for the trial. Also, only a
minority of endovascular patients received GA (7%), likely
favoring good outcomes. Because there is a wide variation in
the use of GA, and because several lines of data associate GA
Downloaded from http://stroke.ahajournals.org/ by guest on September 21, 2017
with worsened outcomes, centers that continue to use GA rou-
tinely may not experience the 44% good outcome rate seen in
REVASCAT.
Disclosures
Dr Smith received compensation from Covidien as member of the
SWIFT-Prime DSMB and from Stryker Neurovascular for member
on the DAWN DSMB. B. Yan received research grant from Johnson
and Johnson and speaker honoraria from Stryker, Inc.
References
1. Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira
A, et al; REVASCAT Trial Investigators. Thrombectomy within 8 hours
after symptom onset in ischemic stroke. N Engl J Med. 2015;372:2296–
2306. doi: 10.1056/NEJMoa1503780.
2. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF,
Yoo AJ, et al; MR CLEAN Investigators. A randomized trial of intraarte-
rial treatment for acute ischemic stroke. N Engl J Med. 2015;372:11–20.
doi: 10.1056/NEJMoa1411587.
3. Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi
N, et al; EXTEND-IA Investigators. Endovascular therapy for ischemic
stroke with perfusion-imaging selection. N Engl J Med. 2015;372:1009–
1018. doi: 10.1056/NEJMoa1414792.
4. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et
al; ESCAPE Trial Investigators. Randomized assessment of rapid endo-
vascular treatment of ischemic stroke. N Engl J Med. 2015;372:1019–
1030. doi: 10.1056/NEJMoa1414905.
5. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al;
SWIFT PRIME Investigators. Stent-retriever thrombectomy after intra-
venous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372:2285–
2295. doi: 10.1056/NEJMoa1415061.
6. Grotta JC, Hacke W. Stroke neurologist’s perspective on the new endovascular
trials. Stroke. 2015;46:1447–1452. doi: 10.1161/STROKEAHA.115.008384.
7. Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD,
et al; Interventional Management of Stroke (IMS) III Investigators.
Endovascular therapy after intravenous t-PA versus t-PA alone for stroke.
N Engl J Med. 2013;368:893–903. doi: 10.1056/NEJMoa1214300.
8. Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, Walker GA, et
al; TREVO 2 Trialists. 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. doi:
10.1016/S0140-6736(12)61299-9.
9. Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, et al;
SWIFT Trialists. Solitaire flow restoration device versus the Merci
Retriever in patients with acute ischaemic stroke (SWIFT): a randomised,
parallel-group, non-inferiority trial. Lancet. 2012;380:1241–1249. doi:
10.1016/S0140-6736(12)61384-1.
10. Trial and cost effectiveness evaluation of intra-arterial thrombectomy in
acute ischemic stroke (THRACE). ClinicalTrials.gov Web site. https://
clinicaltrials.gov/ct2/show/NCT01062698. Accessed August 3, 2015.
11. Molina CA, Chamorro A, Rovira À, de Miquel A, Serena J, Roman
LS, et al. REVASCAT: a randomized trial of revascularization with
SOLITAIRE FR device vs. best medical therapy in the treatment of
acute stroke due to anterior circulation large vessel occlusion present-
ing within eight-hours of symptom onset. Int J Stroke. 2015;10:619–626.
doi: 10.1111/ijs.12157.
12. Khatri P, Hacke W, Fiehler J, Saver JL, Diener HC, Bendszus M, et
al; VISTA-Endovascular Collaboration. State of acute endovascular
therapy: report from the 12th thrombolysis, thrombectomy, and acute
stroke therapy conference. Stroke. 2015;46:1727–1734. doi: 10.1161/
STROKEAHA.115.008782.
Key Words: angiography ◼ endovascular ◼ stents ◼ stroke ◼ thrombectomy
 REVASCAT Trial: Further Advancement in Endovascular Stroke Therapy
Wade S. Smith and Bernard Yan

Stroke. 2015;46:3012-3013; originally published online September 3, 2015;

Downloaded from http://stroke.ahajournals.org/ by guest on September 21, 2017

doi: 10.1161/STROKEAHA.115.010817
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2015 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/46/10/3012

Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.

Reprints: Information about reprints can be found online at:

http://www.lww.com/reprints

Subscriptions: Information about subscribing to Stroke is online at:

http://stroke.ahajournals.org//subscriptions/