Outcomes of Mechanical Endovascular Therapy for Acute

Transcripción

Outcomes of Mechanical Endovascular Therapy for Acute
Ischemic Stroke
A Clinical Registry Study and Systematic Review
Aymeric Rouchaud, MD; Mikael Mazighi, MD, PhD; Julien Labreuche, BST; Elena Meseguer, MD;
Jean-Michel Serfaty, MD; Jean-Pierre Laissy, MD; Philippa C. Lavallée, MD; Lucie Cabrejo, MD;
Céline Guidoux, MD; Bertrand Lapergue, MD; Isabelle F. Klein, MD, PhD;
Jean-Marc Olivot, MD, PhD; Halim Abboud, MD; Olivier Simon, MD, PhD;
Elisabeth Schouman-Claeys, MD; Pierre Amarenco, MD
Downloaded from http://stroke.ahajournals.org/ by guest on December 1, 2016
Background and Purpose—Recanalization is a powerful predictor of stroke outcome in patients with arterial occlusion.
Intravenous recombinant tissue plasminogen activator is limited by its recanalization rate, which may be improved with
mechanical endovascular therapy (MET). However, the benefit and safety of MET remain to be determined. The aim
of this study was to give reliable estimates of efficacy and safety outcomes of MET.
Methods—We analyzed data from our prospective clinical registry and conducted a systematic review of all previous
studies using MET published between January 1966 and November 2009.
Results—From April 2007 to November 2009, 47 patients with acute stroke were treated with MET at Bichat Hospital. The
literature search identified 31 previous studies involving a total of 1066 subjects. In the meta-analysis, including our
registry data, the overall recanalization rate was 79% (95% CI, 73– 84). Meta-analysis of clinical outcomes showed a
pooled estimate of 40% (95% CI, 34 – 46; 27 studies) for favorable outcome, 28% (95% CI, 23–33; 28 studies) for
mortality, and 8% (95% CI, 6 –10; 27 studies) for symptomatic intracranial hemorrhage. The likelihood of a favorable
outcome increased with the use of thrombolysis (OR, 1.99; 95% CI, 1.23–3.22) and with proportion of patients with
isolated middle cerebral artery occlusion (OR per 10% increase, 1.14; 95% CI, 1.04 –1.25).
Conclusions—MET is associated with acceptable safety and efficacy in stroke patients, and it may be a therapeutic option
in those presenting with isolated middle cerebral artery occlusion. (Stroke. 2011;42:1289-1294.)
Key Words: alteplase 䡲 endovascular therapy 䡲 mechanical approach 䡲 recombinant tissue plasminogen activator
䡲 stroke 䡲 thrombectomy
R
ecanalization is a powerful predictor of stroke outcome in
patients with arterial occlusion treated with either intravenous (IV) recombinant tissue plasminogen activator (rt-PA) or
an endovascular approach.1 IV rt-PA is limited by its recanalization rate in the setting of large artery occlusions,2 whereas
intra-arterial thrombolytic administration can reach significantly
higher rates of recanalization in brain infarction patients with a
similar pattern of arterial occlusion.3 These recanalization rates
may be improved up to 87% with mechanical endovascular
therapy (MET).1,4 Although the feasibility of MET in brain
infarction patients has been reported, its safety remains to be
demonstrated. Several devices are now available, but none has
been evaluated in a head-to-head basis versus IV rt-PA, which
remains the reference treatment. Randomized controlled trials,
such as IMS-3, are being performed comparing IV treatment
with an IV plus endovascular approach. Pending the results of
this trial, there are no recommendations for mechanical approaches in brain infarction patients, and MET is still considered
an investigational technique. The aim of this study was to give
reliable estimates of efficacy and safety outcomes for MET in
stroke patients. We therefore analyzed data from our prospective
clinical registry and conducted a systematic review of all
previous studies using this endovascular approach.
Materials and Methods
Bichat Stroke Program
Patients were identified from a prospective clinical registry of stroke
patients treated between February 2002 and November 2009. Before
Received September 12, 2010; accepted November 11, 2010.
From the Department of Neurology and Stroke Centre (A.R., M.M., E.M., P.C.L., L.C., C.G., B.L., J.M.O., O.S., H.A., P.A.), Bichat University
Hospital, Paris, France; INSERM U-698 and Paris-Diderot University (A.R., M.M., J.L., B.L., P.C.L., J.M.S., P.A.); and the Department of Radiology
(J.M.S., J.P.L., I.F.K., E.S.-C.), Bichat University Hospital, Paris, France.
The online-only Data Supplement is available at http://stroke.ahajournals.org/cgi/content/full/STROKEAHA.110.599399/DC1.
Anthony J. Furlan, MD, was the Guest Editor for this paper.
Correspondence to Mikael Mazighi, Department of Neurology and Stroke Centre, Bichat University Hospital, 46, rue Henri Huchard, 75018 Paris,
France. E-mail [email protected]
© 2011 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.110.599399
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Figure 1. Flow diagrams of study
screening process.
April 2007, all patients were treated with IV rt-PA in accordance
with the National Institute of Neurological Disorders and Stroke
design.5 Age was not a contraindication for IV rt-PA. After April
2007, a systematic approach including MET was implemented for
patients with arterial occlusion confirmed on MRA or CT angiography. For patients who presented within 3 hours of symptom onset,
MET with combined IV and intra-arterial rt-PA treatment (0.6 mg/kg
IV and 0.3 mg/kg intra-arterial) was used.1 For patients admitted
after 3 hours, intra-arterial rt-PA and adjunctive MET were considered, if occlusion persisted. In patients with a contraindication to
rt-PA,5 a direct MET approach was considered. No MET was
performed beyond 6 hours after symptom onset. Additional information on data collection and definitions are provided in the
Supplemental Materials (http://stroke.ahajournals.org).
Systematic Review
We identified all observational or interventional studies published
between January 1966 and November 2009 that reported the recanalization and/or clinical outcomes in stroke patients consecutive to
arterial occlusion and treated by MET. We searched the MEDLINE
database using the search terms “endovascular,” “mechanical,”
“thrombectomy,” “clot removal,” “clot disruption in combination
with stroke,” “cerebrovascular disease,” and “brain infarction.”
Searches were restricted to studies published in English and conducted in humans. One author (A.R.) selected potentially relevant
articles based on the title and abstract and obtained the full text for
detailed review. We also searched the reference lists of retrieved
articles and published review articles for additional studies. Study
selection and data extraction methodologies are provided in the
Supplemental Materials.
Statistical Analysis
Statistical testing was conducted at the 2-tailed ␣-level of 0.05,
except tests for homogeneity in which ␣-level of 0.10 was chosen.
Data were analyzed using the SAS software version 9.1 (SAS
Institute) and Cochrane Collaboration’s Review Manager software
package (RevMan edition 4䡠2䡠7). Additional information on the
Bichat Clinical Registry and systematic review analysis are provided
in the Supplemental Materials.
Results
Bichat Clinical Registry
From April 2007 to November 2009, 47 patients with acute
stroke were treated with MET. MET was used as a rescue
approach in 37 patients and as a direct approach in 10
patients. The median time from symptom onset to treatment
was 2.3 hours (range, 1.1– 6.1 hours) in patients with rescue
MET and 4.9 hours (range, 2.8 –15.0 hours) in the remaining
patients.
The baseline characteristics, recanalization rates, and clinical
outcomes, overall and according to indication for MET, are presented in Supplemental Table I (http://stroke.ahajournals.org). Recanalization (Thrombolysis In Myocardial Infarction 2 or 3)
was achieved in 81%, with no difference between the 2
groups. The median time from symptom onset to recanalization was 4.0 hours (range, 2.9 – 6.7 hours) in the rescue
approach group and 6.1 hours (range, 4.8 –12.7 hours) in the
direct approach group. Except a trend toward a lower rate of
early neurological improvement in the direct approach group,
no differences in clinical outcomes were found. Overall, 47%
had a 90-day favorable outcome (mRS score, 0 –2), 19% died
at 3 months, and 40% had hemorrhagic complications within
24 hours. Symptomatic intracranial hemorrhage occurred in 4
patients treated with rescue MET (11%) and in 1 patient
treated with first-line mechanical treatment (10%). In univariate analysis performed in both groups pooled together,
patients with isolated middle cerebral artery (MCA) occlusion more often had a favorable 90-day outcome (62%) than
patients with internal carotid artery occlusion (27%) or
posterior circulation occlusion (33%; P⫽0.04). As reported
previously,1 the rate of 90-day favorable outcome increased
gradually with postprocedure Thrombolysis In Myocardial
Infarction grade flow (␹2 exact test for trend, P⫽0.003).
Systematic Review
The literature search identified 3277 citations. After reviewing the titles and abstracts, 86 articles were read in full and 31
were judged eligible for inclusion (Figure 1). The main
methodological and baseline characteristics of included studies are presented in Supplemental Table II (http://stroke.aha-
Rouchaud et al
Table.
Mechanical Revascularization in Ischemic Stroke
1291
Pooled Rates of Recanalization and Clinical Outcomes
No. of Studies
No. of Patients
Pooled Rates (95% CI)
P*
I 2, %
Partial or complete recanalization
32
1113
78.6 (72.9-83.7)
⬍0.0001
77.5
Complete recanalization
24
580
41.4 (32.1-51.0)
⬍0.0001
80.6
Favorable outcome
27
961
39.9 (34.0-45.9)
⬍0.0001
66.8
Mortality
28
952
27.5 (22.7-32.6)
⬍0.0001
59.7
Outcomes
Main analysis
Hemorrhagic complication
25
919
27.2 (21.9-32.8)
⬍0.0001
65.9
Symptomatic intracranial hemorrhage
27
983
8.1 (6.2-10.4)
0.15
22.0
Favorable outcome
23
877
40.6 (34.4-46.9)
⬍0.0001
66.4
Mortality
22
806
28.3 (23.1-33.8)
0.0009
56.4
Hemorrhagic complication
21
823
28.9 (23.4-34.7)
⬍0.0001
62.7
Symptomatic intracranial hemorrhage
14
685
9.1 (6.6-11.9)
0.22
21.4
Sensitivity analysis†
CI indicates confidence interval.
*P associated with ␹2 test for heterogeneity.
†Restricted to studies with outcome closest to our center definition.
journals.org). In 2 of the included studies, only recanalization
rates could be extracted, because the main purpose was to
describe the subgroup treated by adjunctive stenting for 1
study6 and to describe all patients treated by endovascular
therapy including thrombolysis for the second study.7 The
included studies, which enrolled 1066 subjects (median
sample size, 20; range, 10 –164), were conducted mainly
(⬇64% of cases) in North America. Eight of the studies were
single-arm pilot studies designed to assess the safety and/or
efficacy of mechanical revascularization devices.8 –15 The
remaining 23 studies were case series; most of them (n⫽17)
were classified as retrospective case series analysis.
MET was used as a direct approach in 14 studies (enrolled
448 cases), a rescue approach in 8 studies (enrolled 134
cases), and as both approaches in the 9 remaining studies
(enrolled 484 cases). Of the 23 studies using MET as direct
approach, 7 used MET as first-line treatment for patients who
were eligible for IV rt-PA.12,14,16 –20 As shown in Supplemental Table II, various different MET were used. Of the 31
included studies, 10 used clot retrieval devices as a first
choice of MET and 17 used clot disruption by adapted
devices or by wire manipulation. In the remaining 4 studies,
multimodal MET was used. Adjunctive thrombolysis was
used in 18 studies (including all 14 studies reporting only a
direct approach strategy). The rate of thrombolysis (before
and/or after MET) varied between 7% and 100% across
studies. Among the 28 studies with available data on clot
location, the most frequent target vessel was the MCA (56%
of cases), followed by internal carotid artery (30%) and
posterior circulation (14%). The rate of patients by clot
location varied across studies, and the median admission
NIHSS score ranged between 138 and 24.19
The Table shows the pooled estimates of the rate of
recanalization and clinical outcomes. Outcomes by studies
retrieved are available in Supplemental Table III
(http://stroke.ahajournals.org). In the meta-analysis, including data from our center, the overall recanalization rate
(partial or complete) was 78.6% (95% CI, 72.9 – 83.7). When
only complete recanalization rates were considered (24 stud-
ies), the estimate rate decreased to 41.4% (95% CI, 32.1%–
51.0%). Meta-analysis on clinical outcomes showed a pooled
estimate of 39.9% (95% CI, 34.0 – 45.9; 27 studies) for favorable
outcome, 27.5% (95% CI, 22.7–32.6; 28 studies) for mortality,
and 8.1% (95% CI, 6.2%–10.4%; 27 studies) for symptomatic
intracranial hemorrhage. Sensitivity analyses yielded similar
pooled estimates (Table). A large heterogeneity across studies
was found independently of the outcomes.
In univariate meta-regression analyses, the rates of recanalization and hemorrhagic complications were unrelated to
predefined study-level covariates (all P⬎0.10). Conversely,
the rate of favorable outcome was related to systematic use of
chemical thrombolysis (OR, 1.79; 95% CI, 1.05–3.05;
P⫽0.034) and isolated MCA occlusion rate (OR per 10%
increase, 1.12; 95% CI, 1.01–1.24; P⫽0.036), and the rate of
mortality was related to the use of thrombolysis (OR, 0.47; 95%
CI, 0.30 – 0.75; P⫽0.002). In multivariable meta-regression
analysis, the OR of favorable outcome was 1.99 (95% CI,
1.23–3.22) for the use of thrombolysis and 1.14 (95% CI,
1.04 –1.25) per 10% increase in rate of isolated MCA occlusion.
In addition, as shown in Figure 2, patients with isolated MCA
occlusion had a higher rate of favorable outcome and a lower
rate of mortality than those with other clot locations in the
meta-analysis, including all studies reporting outcome data by
vessel clot location. We found no evidence of major publication
and selection bias by examining the funnel plots of FreemanTukey transformed proportions against their standard error
(Supplemental Figure, http://stroke.ahajournals.org).
Discussion
This systematic review, including our registry data, suggests
a favorable efficacy and safety profile for MET in the
management of acute ischemic stroke patients. Multivariable
meta-regression analysis identified specific conditions associated with a good clinical outcome, including the use of IV
and/or intra-arterial thrombolysis with MET (OR, 1.99; 95%
CI, 1.23–3.22) and the proportion of patients with an isolated
MCA occlusion (OR per 10% increase in rate of isolated
MCA occlusion, 1.14; 95% CI, 1.04 –1.25).
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Figure 2. Crude odds ratios for (A) recanalization, (B) favorable outcome, and (C) mortality for isolated middle cerebral artery occlusion
subgroups in individual and combined observational studies. One study21 with outcome data by vessel clot location could not be
included in the meta-analysis of the recanalization and mortality outcome because all patients achieved recanalization and none died
within 90 days of treatment. OR indicates odds ratio; CI, confidence interval; MCA, middle cerebral artery.
Rouchaud et al
As reported previously,1,4 recanalization is a critical target
to reach. In the Bichat registry, arterial recanalization was
achieved in 81% of patients, with a 90-day favorable outcome
of 47%. When the data from the 31 previous identified studies
were added, similar pooled estimates were found despite
substantial heterogeneity between studies. In the meta-analysis, the overall recanalization rate was 79% (95% CI,
73– 84), and the pooled estimate of favorable clinical outcome was 40% (95% CI, 34 – 46; 27 studies). These results
reinforce the ability of MET to increase rates of recanalization and potentially good clinical outcomes. This latter point
is illustrated by patients presenting with an isolated MCA
occlusion. In the Bichat registry, 62% of these patients had a
favorable outcome at 3 months and a recanalization rate of
84%. Interestingly, the meta-regression analysis showed that
favorable outcome increased in parallel with the proportion of
patients with an isolated MCA occlusion. Patients with an
isolated MCA occlusion represented not only those who benefited the most from MET but also the majority to be treated.
MET may be used as a direct approach (eg, in the case of
a contraindication to rt-PA) and also as a rescue approach
after failure of IV and/or intra-arterial rt-PA. In the Bichat
registry, MET was used predominantly (79%) as a rescue
approach, whereas in the systematic review MET was equally
used as a rescue recanalization strategy or as a first-line
treatment. None of these 2 approaches (rescue or direct)
achieved superiority with respect to recanalization rates or
clinical outcome. In the case of concomitant thrombolysis
(used in 62% patients in the systematic review and in 79% in
the Bichat registry), the meta-regression analysis showed that
the rate of favorable outcome was higher in studies with the
use of thrombolysis (either IV or intra-arterial) than without
(crude OR, 1.79; 95% CI, 1.05–3.05; P⫽0.03). These findings are in accordance with recent data from the MERCI and
Multi MERCI trials, which showed reduced mortality and
time to recanalization with MET in patients treated with IV
thrombolysis.22 The use of combined IV rt-PA and endovascular therapy as performed in our center is probably an
important factor in the observed higher recanalization rates
and favorable outcome in the Bichat registry compared with
those obtained from the systematic review. However, we did
not have access to the individual data of the studies and could
not separate patients who received rt-PA, either IV or
intra-arterial, before MET from those who did not. This is
certainly a limit to appreciate the impact of rt-PA administration before MET on clinical outcomes.
The use of MET did not impact negatively on clinical
outcomes. The meta-analysis showed a pooled estimate of
28% (95% CI, 23–33; 28 studies) for mortality and 8% (95%
CI, 6 –10; 27 studies) for symptomatic intracranial hemorrhage. The use of a specific device or type of MET approach
(ie, clot fragmentation or thrombus capture) was not associated with a better or worse benefit-to-risk ratio. In the
systematic review, there was a wide heterogeneity in the use
of devices for MET, likely explaining the absence of any
significant difference on clinical outcome. In fact, ⬎20 MET
approaches (ie, clot disruption or thrombus capture, adjuvant
thrombolytic therapy, device type) were identified in the
studies analyzed. This heterogeneity in use illustrates the
Mechanical Revascularization in Ischemic Stroke
1293
daily practice of neurointerventionists. It is possible that some
relevant studies were not taken into account in our systematic
review. However, it is unlikely that this potential publication
bias distorted strongly our findings because we found no
evidence of such bias by examining the funnel plots. Finally,
the absence of collected data that has been described to
impact clinical outcome (such as time to recanalization) is
another limitation. As reported previously,1,4 recanalization is
associated with good clinical outcome, but time from symptom onset to recanalization is probably a better predictor of
good outcome.1,23
The present meta-analysis included mainly comparative
case reports and case series with nonrandomized data; no
randomized controlled trials have been performed to evaluate
devices used in MET. Although no randomized controlled
trials have been completed, some are ongoing, either comparing the endovascular approach (including MET) with the
gold standard or conducting a head-to-head comparison
between different MET devices. The results of these trials
may be affected by the delay between IV rt-PA treatment and
the decision to perform rescue MET, because rescue MET
will only be used in cases of no recanalization after IV rt-PA
treatment. Because time to recanalization is the most powerful predictor of favorable outcome, any delay in recanalization is followed by a decreased rate of 90-day favorable
outcome. The use of an endovascular approach during IV
rt-PA treatment (ie, femoral puncture and navigation to the
intracranial clot performed immediately after the IV bolus)
would decrease the time to recanalization.
Conclusions
Good candidates for MET are those with an isolated MCA
occlusion and patients treated in association with
thrombolysis. These elements may be considered as inclusion
criteria in the design of future randomized controlled trials
evaluating MET versus IV rt-PA alone. Pending the results of
such trials, the present data support MET as a therapeutic
alternative in patients with acute stroke.
Acknowledgments
M.M., J.M.O., and P.A. participated in the conception and design of
the study. A.R., J.L., M.M., and P.A. analyzed and interpreted the
data. M.M., J.M.S., E.M., P.L., L.C., C.G., B.L., I.F.K., J.M.O., O.S.,
H.A., and J.P.L. were responsible for the provision of study material
or patients. M.M. and E.M. were responsible for collection, assembly, and possession of the raw data. J.L. was responsible for
statistical expertise. A.R., M.M., J.L., and P.A. were responsible for
drafting of the article. E.S.C. and P.A. were responsible for critical
revision of the manuscript and for important intellectual content.
P.A. was responsible for final approval of the article for publication
and for obtaining funding for the study. Sophie Rushton-Smith, PhD,
provided editorial assistance on the final version of this manuscript,
including editing, checking content and language, and formatting.
Sources of Funding
Sophie Rushton-Smith was funded by SOS Attaque Cérébrale.
Disclosure
None.
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References
1. Mazighi M, Serfaty JM, Labreuche J, Laissy JP, Meseguer E, Lavallée
PC, Cabrejo L, Slaoui T, Guidoux C, Lapergue B, Klein IF, Olivot JM,
Abboud H, Simon O, Niclot P, Nifle C, Touboul PJ, Raphaeli G, Gohin
C, Claeys ES, Amarenco P, RECANALISE investigators. Comparison of
intravenous alteplase with a combined intravenous-endovascular
approach in patients with stroke and confirmed arterial occlusion
(RECANALISE study): a prospective cohort study. Lancet Neurol. 2009;
8:802– 809.
2. del Zoppo GJ, Poeck K, Pessin MS, Wolpert SM, Furlan AJ, Ferbert A,
Alberts MJ, Zivin JA, Wechsler L, Busse O. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol.
1992;32:78 – 86.
3. Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin
M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F. Intra-arterial
prourokinase for acute ischemic stroke. The PROACT II study: A randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism.
JAMA. 1999;282:2003–2011.
4. Rha JH, Saver JL. The impact of recanalization on ischemic stroke
outcome: a meta-analysis. Stroke. 2007;38:967–973.
5. 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.
6. Sauvageau E, Samuelson RM, Levy EI, Jeziorski AM, Mehta RA,
Hopkins LN. Middle cerebral artery stenting for acute ischemic stroke
after unsuccessful Merci retrieval. Neurosurgery. 2007;60:701–706.
7. Prabhakaran S, Chen M, Choi JH, Mangla S, Lavine SD, Pile-Spellman
J, Meyers PM, Chong JY. Major neurologic improvement following
endovascular recanalization therapy for acute ischemic stroke. Cerebrovasc Dis. 2008;25:401– 407.
8. Levy EI, Siddiqui AH, Crumlish A, Snyder KV, Hauck EF, Fiorella DJ,
Hopkins LN, Mocco J. First Food and Drug Administration-approved
prospective trial of primary intracranial stenting for acute stroke: SARIS
(stent-assisted recanalization in acute ischemic stroke). Stroke. 2009;40:
3552–3556.
9. Penumbra Pivotal Stroke Trial Investigators. 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.
10. Bose A, Henkes H, Alfke K, Reith W, Mayer TE, Berlis A, Branca V, Sit
SP, Penumbra Phase 1 Stroke Trial Investigators. The Penumbra System:
a mechanical device for the treatment of acute stroke due to thromboembolism. AJNR Am J Neuroradiol. 2008;29:1409 –1413.
11. Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS,
Lutsep HL, Rymer MM, Higashida RT, Starkman S, Gobin YP, Multi
MERCI Investigators, Frei D, Grobelny T, Hellinger F, Huddle D,
Kidwell C, Koroshetz W, Marks M, Nesbit G, Silverman IE. Mechanical
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
thrombectomy for acute ischemic stroke: final results of the Multi
MERCI trial. Stroke. 2008;39:1205–1212.
Mayer TE, Hamann GF, Schulte-Altedorneburg G, Brückmann H.
Treatment of vertebrobasilar occlusion by using a coronary waterjet
thrombectomy device: a pilot study. AJNR Am J Neuroradiol. 2005;26:
1389 –1394.
Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP, Lutsep
HL, Nesbit GM, Grobelny T, Rymer MM, Silverman IE, Higashida RT,
Budzik RF, Marks MP; MERCI Trial Investigators. Safety and efficacy of
mechanical embolectomy in acute ischemic stroke: results of the MERCI
trial. Stroke. 2005;36:1432–1438.
Berlis A, Lutsep H, Barnwell S, Norbash A, Wechsler L, Jungreis CA,
Woolfenden A, Redekop G, Hartmann M, Schumacher M. Mechanical
thrombolysis in acute ischemic stroke with endovascular photoacoustic
recanalization. Stroke. 2004;35:1112–1116.
Mahon BR, Nesbit GM, Barnwell SL, Clark W, Marotta TR, Weill A,
Teal PA, Qureshi AI. North American clinical experience with the EKOS
MicroLysUS infusion catheter for the treatment of embolic stroke. AJNR
Am J Neuroradiol. 2003;24:534 –538.
Devlin TG, Baxter BW, Feintuch TA, Desbiens NA. The Merci Retrieval
System for acute stroke: the Southeast Regional Stroke Center experience. Neurocrit Care. 2007;6:11–21.
Bergui M, Stura G, Daniele D, Cerrato P, Berardino M, Bradac GB.
Mechanical thrombolysis in ischemic stroke attributable to basilar artery
occlusion as first-line treatment. Stroke. 2006;37:145–150.
Imai K, Mori T, Izumoto H, Takabatake N, Kunieda T, Shimizu H,
Watanabe M. Clot removal therapy by aspiration and extraction for acute
embolic carotid occlusion. AJNR Am J Neuroradiol. 2006;27:1521–1527.
Sorimachi T, Fujii Y, Tsuchiya N, Nashimoto T, Harada A, Ito Y, Tanaka
R. Recanalization by mechanical embolus disruption during intra-arterial
thrombolysis in the carotid territory. AJNR Am J Neuroradiol. 2004;25:
1391–1402.
Nakano S, Iseda T, Yoneyama T, Kawano H, Wakisaka S. Direct percutaneous transluminal angioplasty for acute middle cerebral artery trunk
occlusion: an alternative option to intra-arterial thrombolysis. Stroke.
2002;33:2872–2876.
Barnwell SL, Clark WM, Nguyen TT, O’Neill OR, Wynn ML, Coull BM.
Safety and efficacy of delayed intraarterial urokinase therapy with
mechanical clot disruption for thromboembolic stroke. AJNR Am J Neuroradiol. 1994;15:1817–1822.
Shi ZS, Loh Y, Walker G, Duckwiler GR, MERCI and Multi MERCI
Investigators. Endovascular thrombectomy for acute ischemic stroke in
failed intravenous tissue plasminogen activator versus non-intravenous
tissue plasminogen activator patients: revascularization and outcomes
stratified by the site of arterial occlusions. Stroke. 2010;41:1185–1192.
Khatri P, Abruzzo T, Yeatts SD, Nichols C, Broderick JP, Tomsick TA,
IMS I and II Investigators. Good clinical outcome after ischemic stroke
with successful revascularization is time-dependent. Neurology. 2009;73:
1066 –1072.
Outcomes of Mechanical Endovascular Therapy for Acute Ischemic Stroke: A Clinical
Registry Study and Systematic Review
Aymeric Rouchaud, Mikael Mazighi, Julien Labreuche, Elena Meseguer, Jean-Michel Serfaty,
Jean-Pierre Laissy, Philippa C. Lavallée, Lucie Cabrejo, Céline Guidoux, Bertrand Lapergue,
Isabelle F. Klein, Jean-Marc Olivot, Halim Abboud, Olivier Simon, Elisabeth Schouman-Claeys
and Pierre Amarenco
Stroke. 2011;42:1289-1294; originally published online March 24, 2011;
doi: 10.1161/STROKEAHA.110.599399
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
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SUPPLEMENTAL MATERIAL
1
Supplemental Methods
Bichat Stroke Program
Data Collection and Definitions
Patient demographics, vascular risk factors, laboratory and imaging findings, vital signs before
treatment, severity of ischemic stroke, and clinical outcomes were collected using a structured
questionnaire. Hypertension and hypercholesterolaemia were defined by treatment history. Patients
were classified as diabetic if they had been treated for either type 1 or type 2 diabetes. Smoking
history was coded as never, previous, or current. The severity of ischaemic stroke was assessed by
NIHSS scores, which were prospectively collected at 1, 3, and 24 h after initiation of treatment. Time
from symptom onset (or from when the patient was last seen in a healthy condition by any witness) to
initiation of treatment was also recorded. All patients had a follow-up CT or magnetic resonance
imaging (MRI) scan 24 hours after starting treatment. Symptomatic intracerebral hemorrhage was
defined as a hemorrhage seen on the follow-up CT/MRI scan associated with an increase of ≥4 points
1
in the NIHSS score according to the European Cooperative Acute Stroke Study criteria.
Recanalization was considered achieved when the Thrombolysis In Myocardial Infarction (TIMI) score
was 2 (partial) or 3 (complete). Functional outcome was assessed at 3 months by a senior vascular
neurologist using the modified Rankin scale (mRS) dichotomized into favorable (mRS 0–2) and
unfavorable (mRS 3–6) outcomes.
Systematic Review
Study Selection
Studies were selected using the following criteria: 1) involving subjects aged ≥18 years; 2) that
reported recanalization rates or clinical outcomes among stroke patients treated by MET; 3)
retrospective or prospective studies with at least 10 patients with an angiographically documented
arterial occlusion. We did not select studies according to the clot location, timing of assessment of
recanalisation, or the reported outcomes definitions. We also screened duplicate publications that
drew on the same datasets (i.e. data overlapped with that in other included studies); only the
publication with the most complete data was included.
Data Extraction
Data were extracted independently by two authors (A.R., J.L.) using a standardized form and any
disagreement was resolved by consensus. We did not contact the authors of the studies to request
incomplete or unpublished data. The following data were collected: report characteristics (first
author’s name, journal, year of publication), study design (country, study period, number of centers,
retrospective analysis), indication for MET, type of MET, time from symptom onset to initiation of MET,
rates of chemical thrombolysis (IV or IA), study sample, data and definition on outcomes among the
entire study sample and by vessel location (recanalisation rates, functional outcome, mortality,
symptomatic and asymptomatic hemorrhagic complication). When available, we extracted the degree
2
3
of recanalization (i.e. partial vs. complete) defined by the TIMI scale, TICI scale, or author’s
definitions.
We differentiated two types of indication for MET: a rescue approach after failure of chemical
thrombolysis and a direct approach as a first-line treatment including patients with a contraindication
to chemical thrombolysis (administered IV or IA). Three types of mechanical approach were defined:
mechanical clot-retrieval device, mechanical clot disruption by adapted device, and mechanical clot
disruption using wire manipulations. The target vessels were classified into three groups: isolated
MCA occlusion, internal carotid artery (ICA) occlusion (isolated or in tandem with MCA), and posterior
circulation occlusion (vertebral, basilar and posterior cerebral arteries).
Statistical Analysis
Bichat Clinical Registry
Data are presented as median (range) for continuous variables and percentage (number) for
dichotomous variables for all study samples and according to indication for mechanical clot retrieval.
Univariate comparisons were made using Fisher’s exact test or the Mann-Whitney U test, where
appropriate. The Chi-square exact test for trend was used to study the impact of TIMI flow grade on
favorable outcome.
Systematic Review
To determine the pooled proportions of different outcomes (recanalization, functional outcome,
mortality, hemorrhagic complications), we transformed individual proportions into a quantity using the
2
4
Freeman-Tukey variance stabilizing arcsine transformation. For all outcomes, we quantified betweenstudy heterogeneity using a homogeneity test based on Cochran’s Q statistics and by calculating the
I² statistics. Since we anticipated wide heterogeneity in terms of the various study characteristics, the
5
DerSimonian-Laird random-effects model was used to pool the transformed proportions, followed by
a back-transformation to provide the pooled proportion in original scale. For each clinical outcome, we
performed sensitivity analysis by restricting the meta-analysis to the studies using the same definition
applied in our center. We assessed potential publication and selection bias for each outcome by
examining the funnel plots of the Freeman-Tukey transformed proportion against its standard error.
To explore potential sources of heterogeneity, we performed meta-regression analyses using logistic6
normal random models ; the following study-level covariates were examined : indication to
mechanical revascularisation (direct versus rescue approach [including in this group the studies using
both approach]), median time to treatment (≤ 4.5 hours vs. >4.5 hours) mean age, proportion of men,
median admission NIHSS score, systematic use of chemical thrombolysis (100% of patients treated,
pre-or post mechanical procedure) and proportion of isolated MCA occlusion. Since in our center,
patients with isolated MCA occlusion had better prognosis than remaining patients, we calculated the
odds ratio (OR) of recanalisation, favourable outcome and mortality associated with isolated MCA
occlusion (using other vessel locations as reference) for studies reporting outcome data by vessel clot
locations (including data from our center). Individual ORs were combined using the Mantel-Haenszel
5
fixed-effect model after checking homogeneity assumption by the Cochran’s Q test.
3
Supplemental Tables
Supplemental Table I. Bichat Clinical Registry: Baseline Characteristics, Recanalization and Clinical
Outcomes.
P
All
Rescue
Direct Approach
(n=47)
approach
(n=10)
(n=37)
Age, y, median (range)
69 (26-88)
72 (31-88)
54 (26-85)
0.04
Men
23 (48.9)
17 (46.0)
6 (60.0)
0.49
Medical history
Hypertension
23 (48.9)
21 (56.8)
2 (20.0)
0.07
Diabetes
7 (14.9)
5 (13.5)
2 (20.0)
0.63
Hypercholesterolemia
11 (23.4)
9 (24.3)
2 (20.0)
1.00
Current or former smokers
9 (19.2)
7 (18.9)
2 (20.0)
1.00
Clinical measure, median (range)
Platelet count, 1000/µL
230 (129-552)
223 (129-312)
260 (133-552)
0.07
Blood glucose level, mg/dL
116 (77-286)
115 (79-286)
139 (77-178)
0.52
Systolic BP, mmHg
145 (100-182)
146 (100-182)
127 (107-181)
0.44
Diastolic BP, mmHg
83 (50-98)
83 (54-98)
71 (50-89)
0.09
NIHSS score
17 (1-37)
17 (1-24)
19 (10-37)
0.39
Site of occlusion
Carotid artery (Isolated or in tandem with
15 (31.9)
11 (29.7)
4 (40.0)
0.48
MCA)
Isolated MCA
26 (55.3)
22 (59.5)
4 (40.0)
Posterior circulation occlusion
6 (12.8)
4 (10.8)
2 (20.0)
Recanalisation
TIMI 2 or 3 flow
38 (80.9)
29 (78.4)
9 (90.0)
0.66
TIMI 3 flow
28 (59.6)
22 (59.5)
6 (60.0)
1.00
Clinical outcomes
Early neurological improvement
23 (48.9)
21 (56.8)
2 (20.0)
0.07
90-day favourable outcome
22 (46.8)
18 (48.7)
4 (40.0)
0.73
90-day mortality
9 (19.2)
6 (16.2)
3 (30.0)
0.38
Haemorrhagic complication
19 (40.4)
16 (43.2)
3 (30.0)
0.72
Symptomatic intracranial haemorrhage
5 (10.6)
4 (10.8)
1 (10.0)
1.00
Values are expressed as number (percentage) unless otherwise indicated. BP indicates blood pressure;
NIHSS, national institutes of health stroke scale; IA, intra-arterial; MCA, middle cerebral artery; TIMI,
thrombolysis in myocardial ischemia ischemia. Favourable outcome defined as an mRS score of 2 or less.
Early neurological improvement defined as NIHSS score 0–1 at 24 hours or a decrease of 4 or more points in
NIHSS score at 24 hours.
4
Supplemental Table II. Design and Baseline Characteristics of Included Studies
Country
Study period
Source, year
Brekenfeld 2009
8
Jeong 2009
Leker 2009
Levy 2009
7
9
10
Penumbra Pivotal
11
Stroke Trial 2009
Struffert 2009
Yoon 2009
12
13
14
Bose 2008
Kim 2008
15
Nogueira 2008
16
Prabhakaran 2008
Smith 2008
18
Dabitz 2007
Devlin 2007
19
20
Qureshi 2007
21
Sauvageau 2007
23
Bergui 2006
Imai 2006
17
24
22
Switzerland (Single
center) 2006-2007
Korea (Single center)
2006-2008
Mechanical Features
Sample Indication
Method
Size
12
Direct and Clot disruption by adapted device +/rescue
Clot retrieval (n=4)
Clot disruption by wire manipulations +/42
Rescue
Clot disruption by adapted device (n=21)
Israel (Single center)
50
United States (Single
center) 2008
Europe/North America
(multicenter) 20062007
Germany (Single
center) 2007-2008
2006-2007
Europe (multicenter)
20
19
center) 2003-2006
United States (singlecenter) 2002-2005
North America
Germany (singlecenter) 2002-2005
center) 2004-2005
center) 2003-2004
Italy (Single-center)
2003-2004
Japan (Single center)
Direct and
rescue
Direct and
rescue
Direct and
rescue
Any (alone or multimodal mechanical
therapy)
Clot disruption by adapted device
15
Rescue
Clot retrieval
12
Rescue
20
12
Direct and
rescue
Direct and
rescue
Rescue
Clot disruption by wire manipulations +/Clot disruption by adapted device
Clot retrieval
49
Direct
164
Direct and
rescue
Clot disruption by adapted device and by
wire manipulations
therapy)
Clot retrieval +/Clot disruption by adapted device (n=9)
10
Rescue
25
Direct
17
Rescue
36
Direct
12
Direct
14
Direct
Clot retrieval ±
Clot disruption by adapted device and/or by
wire manipulations
Clot retrieval ±
Clot retrieval or Clot disruption by wire
manipulation
Clot retrieval ±
125
Clot retrieval +/Clot disruption by adapted device
Clot disruption by wire manipulations
Mean
Age
y
63
Men
%
58
Median
Baseline
NIHSS
14
Median
Clot location,%
time to
ICA Isolated
treatment
MCA
4.5 h
17† 33
Posterior
arteries
50
…
…
…
3.9 h
24
69
7
46%
(IA)
25%
(IV, IA)
…
62
46
20
6.0 h
44
56
0
63
30
13
4.9 h
5
80
15
64
51
18 *
4.3 h *
18
70
12
100%
(IV, IV/IA)
100%
(IV/IA)
≈50%
(IV, IA)
100%
(IA, IV/IA)
100%
(IV, IA, IV/IA)
51%
(IA)
53%
(IV, IA, IV/IA)
60
60
15
2.5 h
33
47
20
70
75
17
3.8 h
17
67
16
60
60
21 *
…
33
24
43
65
68
17
5.2 h
0
100
0
66
42
17
5.9 h
42
16
42
…
…
…
…
…
…
…
68
43
19
4.3 h
32
60
8
100%
(IV, IA, IV/IA)
60%
(IA)
100%
(IV)
…
56
90
18
…
100
0
0
63
64
18
4.3 h
44
48
8
66
35
15
3.8 h
…
…
…
…
…
…
…
…
…
…
100%
(IA)
7%
64
58
23
5.5 h
0
0
100
76
57
20
3.0 h
100
0
0
Thrombolysis
Therapy, %
67%
(IA)
100%
(IV/IA)
5
Kim 2006
25
Abou-Chebl 2005
Mangiafico 2005
Mayer 2005
Noser 2005
Smith 2005
Berlis 2004
27
28
29
30
Versnick 2005
31
32
Sorimachi 2004
Mahon 2003
33
34
Nakano 2002
35
Qureshi 2002
36
Barnwell 1994
37
Total or mean
26
2003-2005
center) 2002-2004
United States
(Single center)
Italy (Single-center)
2003-2004
Germany (Single
center) 1999-2003
center) 1998-2003
United States
center) 2002-2003
Europe/North America
(multicenter)
Japan (Single center)
2001-2003
North America
(Multicenter) 20002001
Japan (single-center)
1993-2002
center) 2000-2001
24
Clot retrieval
12
Direct and
rescue
Rescue
21
Direct
12
Direct
50
151
Direct and
rescue
Direct
Clot disruption by wire manipulations ±
Clot retrieval ±
10
Direct
Clot retrieval
34
Direct
23
Direct
Clot disruption by wire manipulation
14
Direct
34
Direct
14
Rescue
13
Direct
wire manipulations
Clot disruption by wire manipulations
1066
therapy)
wire manipulations
(IA)
29%
(IV, IA)
100%
(IV, IA, IV/IA)
100%
(IA)
42%
(IA)
98%
(IV, IA, IV/IA)
≈34%
(IA)
64
58
21
5.2 h
38
58
4
66
51
18
3.5 h
42
50
8
67
57
20
4.9 h
33
33
33
56
75
21
…
0
0
100
60
64
18
4.3 h
40
60
0
67
54
20 *
4.3 h *
33
57
10
30%
(IA)
50%
(IV, IA)
100%
(IA)
100%
(IA)
62
90
21
5.0 h
30
30
40
68
50
19
6.4 h *
30
35
35
73
65
24
1.8 h
48
52
0
64
50
18
4.5 h
36
36
28
62%
(IV, IA)
100%
(IV, IA)
100%
(IA)
62%
69
71
17
…
0
100
0
63
64
21
3.8 h
36
57
7
50
54
22
6.5 h
15
62
23
65
54
19
4.5 h
30
56
14
* values are means; † including one patient with isolated anterior cerebral artery occlusion
IV indicates intravenous thrombolysis; IA, intra-arterial thrombolysis; ICA, internal carotid artery; MCA, middle cerebral artery; NIHSS, national institutes of health stroke
scale.
6
Supplemental Table III. Rates of recanalization and clinical outcomes In Included Studies
Recanalisation
Functional
Source, year
Any
Complete
outcome
Mortality
7
Brekenfeld 2009
92
25
25
33
8
Jeong 2009
81
…
…
…
9
Leker 2009
56
38
34
26
10
Levy 2009
100
60
60 *
25 *
11
Penumbra Pivotal Stroke Trial 2009
82
27
25
33
12
Struffert 2009
80
47
33
20
13
Yoon 2009
100
25
75
0
14
Bose 2008
100
52
35 *
45 *
15
Kim 2008
95
0
58
16
16
Nogueira 2008
92
17
42
33
17
Prabhakaran 2008
76
...
...
...
18
Smith 2008
68
…
36
34
19
Dabitz 2007
70
50
40 *
10 *
20
Devlin 2007
56
56
24
36
21
Qureshi 2007
59
24
29
6
22
Sauvageau 2007
72
…
…
…
23
Bergui 2006
92
58
25
33
24
Imai 2006
50
29
43
14
25
Kim 2006
62
21
25
29
26
Abou-Chebl 2005
92
67
…
17 *
27
Mangiafico 2005
81
52
62
29
28
Mayer 2005
100
83
33
42
29
Noser 2005
74
8
54
10 *
30
Smith 2005
56
…
28
44
31
Versnick 2005
80
80
30
50
32
Berlis 2004
41
...
15 *
38 *
33
Sorimachi 2004
96
...
57
9
34
Mahon 2003
86
36
36
36
35
Nakano 2002
91
...
74
...
36
Qureshi 2002
79
79
43
50
37
Barnwell 1994
77
46
…
23
Clinical outcomes defined by same criteria applied in our center except as marked by *
Hemorrhagic complications
Any
Symptomatic
0
0
40
10 *
20 *
2*
15
5
28
11
47
0
…
0*
40 *
10
37
11
42
0
...
...
40
10
40
…
32
28
18
0
…
…
8
...
0*
0*
46
8
17 *
8*
24
14 *
42
25 *
…
8*
33
7
...
0*
12
6
...
...
…
14 *
29
3*
0
0*
23
0*
7
Supplemental Figure Legends
Supplemental Figure. Funnel plots for (A) partial or complete recanalization; (B) complete
recanalization; (C) favorable outcome; (D) mortality; (E) hemorrhagic complications; and (F)
symptomatic intracranial hemorrhage. Effect size indicates the Freeman-Tukey transformed
proportion expressed in degrees.
8
Supplemental References
1. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E,
Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. 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.
2. TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. N
Engl J Med. 1985;312:932-936.
3. Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, Dillon W, Warach S,
Broderick J, Tilley B, Sacks D; Technology Assessment Committee of the American Society
of Interventional and Therapeutic Neuroradiology; Technology Assessment Committee of the
Society of Interventional Radiology. Trial design and reporting standards for intra-arterial
cerebral thrombolysis for acute ischemic stroke. Stroke. 2003;34:e109-e137.
4. Freeman M, Tukey J. Transformations related to the angular and the square root. Ann Math
Statist 1950;21:607-611.
5. Deeks JJ, Altman DG, Bradburn MJ. Statistical methods for examining heterogeneity and
combining results from several studies in meta-analysis. In: Egger M, Davey Smith G, Altman
DG(Eds). Systematic Reviews in Health Care: Meta-Analysis in Context (2nd edition):
London: BMJ Publication Group, 2001.
6. Thompson SG, Sharp SJ. Explaining heterogeneity in meta-analysis: a comparison of
methods. Stat Med. 1999;18:2693-2708.
7. Brekenfeld C, Schroth G, Mattle HP, Do DD, Remonda L, Mordasini P, Arnold M, Nedeltchev
K, Meier N, Gralla J. Stent placement in acute cerebral artery occlusion: use of a selfexpandable intracranial stent for acute stroke treatment. Stroke. 2009;40:847-852.
8. Jeong SY, Park SS, Koh EJ, Eun JP, Choi HY. Multimodal therapy for patients with acute
ischemic stroke : outcomes and related prognostic factors. J Korean Neurosurg Soc.
2009;45:360-368.
9. Leker RR, Eichel R, Arkadir D, Gomori JM, Raphaeli G, Ben-Hur T, Cohen JE. Multi-modal
reperfusion therapy for patients with acute anterior circulation stroke in Israel. Stroke.
2009;40:3627-3630.
10. Levy EI, Siddiqui AH, Crumlish A, Snyder KV, Hauck EF, Fiorella DJ, Hopkins LN, Mocco J.
First Food and Drug Administration-approved prospective trial of primary intracranial stenting
for acute stroke: SARIS (stent-assisted recanalization in acute ischemic stroke). Stroke.
2009;40:3552-3556.
11. Penumbra Pivotal Stroke Trial Investigators. 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.
12. Struffert T, K√∂hrmann M, Engelhorn T, Nowe T, Richter G, Schellinger PD, Schwab S,
Doerfler A. Penumbra Stroke System as an "add-on" for the treatment of large vessel
occlusive disease following thrombolysis: first results. Eur Radiol. 2009;19:2286-2293.
13. Yoon W, Park MS, Cho KH. Low-Dose Intra-Arterial Urokinase and Aggressive Mechanical
Clot Disruption for Acute Ischemic Stroke after Failure of Intravenous Thrombolysis. AJNR
AJNR Am J Neuroradiol. 2010;31:161-164.
14. Bose A, Henkes H, Alfke K, Reith W, Mayer TE, Berlis A, Branca V, Sit SP; Penumbra Phase
1 Stroke Trial Investigators. The Penumbra System: a mechanical device for the treatment of
acute stroke due to thromboembolism. AJNR Am J Neuroradiol. 2008;29:1409-1413.
15. Kim DJ, Kim DI, Byun JS, Jung JY, Suh SH, Kim EY, Lee KY, Heo JH. Simple microwire and
microcatheter mechanical thrombolysis with adjuvant intraarterial urokinase for treatment of
hyperacute ischemic stroke patients. Acta Radiol. 2008;49:351-357.
16. Nogueira RG, Schwamm LH, Buonanno FS, Koroshetz WJ, Yoo AJ, Rabinov JD, Pryor JC,
Hirsch JA. Low-pressure balloon angioplasty with adjuvant pharmacological therapy in
patients with acute ischemic stroke caused by intracranial arterial occlusions. Neuroradiology.
2008;50:331-340.
17. Prabhakaran S, Chen M, Choi JH, Mangla S, Lavine SD, Pile-Spellman J, Meyers PM, Chong
JY. Major neurologic improvement following endovascular recanalization therapy for acute
ischemic stroke. Cerebrovasc Dis. 2008;25:401-407.
18. Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS, Lutsep HL, Rymer MM,
Higashida RT, Starkman S, Gobin YP; Multi MERCI Investigators, Frei D, Grobelny T,
Hellinger F, Huddle D, Kidwell C, Koroshetz W, Marks M, Nesbit G, Silverman IE. Mechanical
9
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke.
2008;39:1205-1212.
Dabitz R, Triebe S, Leppmeier U, Ochs G, Vorwerk D. Percutaneous recanalization of acute
internal carotid artery occlusions in patients with severe stroke. Cardiovasc Intervent Radiol.
2007;30:34-41.
Devlin TG, Baxter BW, Feintuch TA, Desbiens NA. The Merci Retrieval System for acute
stroke: the Southeast Regional Stroke Center experience. Neurocrit Care. 2007;6(1):11-21.
Qureshi AI, Janjua N, Kirmani JF, Harris-Lane P, Suri MF, Zhou J, Divani AA. Mechanical
disruption of thrombus following intravenous tissue plasminogen activator for ischemic stroke.
J Neuroimaging. 2007;17:124-130.
Sauvageau E, Samuelson RM, Levy EI, Jeziorski AM, Mehta RA, Hopkins LN. Middle
cerebral artery stenting for acute ischemic stroke after unsuccessful Merci retrieval.
Neurosurgery. 2007;60:701-706.
Bergui M, Stura G, Daniele D, Cerrato P, Berardino M, Bradac GB. Mechanical thrombolysis
in ischemic stroke attributable to basilar artery occlusion as first-line treatment. Stroke.
2006;37(1):145-50.
Imai K, Mori T, Izumoto H, Takabatake N, Kunieda T, Shimizu H, Watanabe M. Clot removal
therapy by aspiration and extraction for acute embolic carotid occlusion. AJNR Am J
Neuroradiol. 2006;27:1521-1527.
Kim D, Jahan R, Starkman S, Abolian A, Kidwell CS, Vinuela F, Duckwiler GR, Ovbiagele B,
Vespa PM, Selco S, Rajajee V, Saver JL. Endovascular mechanical clot retrieval in a broad
ischemic stroke cohort. AJNR Am J Neuroradiol. 2006;27:2048-2052.
Abou-Chebl A, Bajzer CT, Krieger DW, Furlan AJ, Yadav JS. Multimodal therapy for the
treatment of severe ischemic stroke combining GPIIb/IIIa antagonists and angioplasty after
failure of thrombolysis. Stroke. 2005;36:2286-2288.
Mangiafico S, Cellerini M, Nencini P, Gensini G, Inzitari D. Intravenous glycoprotein IIb/IIIa
inhibitor (tirofiban) followed by intra-arterial urokinase and mechanical thrombolysis in stroke.
Mayer TE, Hamann GF, Schulte-Altedorneburg G, Brückmann H. Treatment of
vertebrobasilar occlusion by using a coronary waterjet thrombectomy device: a pilot study.
Noser EA, Shaltoni HM, Hall CE, Alexandrov AV, Garami Z, Cacayorin ED, Song JK, Grotta
JC, Campbell MS 3rd. Aggressive mechanical clot disruption: a safe adjunct to thrombolytic
therapy in acute stroke? Stroke. 2005;36:292-296.
Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP, Lutsep HL, Nesbit GM,
Grobelny T, Rymer MM, Silverman IE, Higashida RT, Budzik RF, Marks MP; MERCI Trial
Investigators. Safety and efficacy of mechanical embolectomy in acute ischemic stroke:
results of the MERCI trial. Stroke. 2005;36:1432-1438.
Versnick EJ, Do HM, Albers GW, Tong DC, Marks MP. Mechanical thrombectomy for acute
stroke. AJNR Am J Neuroradiol. 2005;26:875-879.
Berlis A, Lutsep H, Barnwell S, Norbash A, Wechsler L, Jungreis CA, Woolfenden A,
Redekop G, Hartmann M, Schumacher M. Mechanical thrombolysis in acute ischemic stroke
with endovascular photoacoustic recanalization. Stroke. 2004;35:1112-1116.
Sorimachi T, Fujii Y, Tsuchiya N, Nashimoto T, Harada A, Ito Y, Tanaka R. Recanalization by
mechanical embolus disruption during intra-arterial thrombolysis in the carotid territory. AJNR
Am J Neuroradiol. 2004;25:1391-1402.
Mahon BR, Nesbit GM, Barnwell SL, Clark W, Marotta TR, Weill A, Teal PA, Qureshi AI.
North American clinical experience with the EKOS MicroLysUS infusion catheter for the
treatment of embolic stroke. AJNR Am J Neuroradiol. 2003;24:534-538.
Nakano S, Iseda T, Yoneyama T, Kawano H, Wakisaka S. Direct percutaneous transluminal
angioplasty for acute middle cerebral artery trunk occlusion: an alternative option to intraarterial thrombolysis. Stroke. 2002;33:2872-2876.
Qureshi AI, Siddiqui AM, Suri MF, Kim SH, Ali Z, Yahia AM, Lopes DK, Boulos AS, Ringer
AJ, Saad M, Guterman LR, Hopkins LN. Aggressive mechanical clot disruption and low-dose
intra-arterial third-generation thrombolytic agent for ischemic stroke: a prospective study.
Neurosurgery. 2002;51:1319-1327.
Barnwell SL, Clark WM, Nguyen TT, O'Neill OR, Wynn ML, Coull BM. Safety and efficacy of
delayed intraarterial urokinase therapy with mechanical clot disruption for thromboembolic
stroke. AJNR Am J Neuroradiol. 1994;15:1817-1822.
10
32
Stroke
Vol. 4, No. 3
Abstract 8
30
Stroke 日本語版 Vol. 6, No. 2
Abstract
急性虚血性脳卒中の機械的血管内治療の転帰
— 臨床登録研究および系統的レビュー
Outcomes of Mechanical Endovascular Therapy for Acute Ischemic Stroke
― A Clinical Registry Study and Systematic Review
Aymeric Rouchaud, MD1,2; Mikael Mazighi, MD, PhD1,2; Julien Labreuche, BST2; Elena Meseguer, MD1;
Jean-Michel Serfaty, MD2,3; Jean-Pierre Laissy, MD3; Philippa C. Lavallée, MD1,2; Lucie Cabrejo, MD1; Céline
Guidoux, MD1; Bertrand Lapergue, MD1,2; Isabelle F. Klein, MD, PhD3; Jean-Marc Olivot, MD, PhD1; Halim
Abboud, MD1; Olivier Simon, MD, PhD1; Elisabeth Schouman-Claeys, MD3; Pierre Amarenco, MD1,2
1 3 Department of Neurology and Stroke Centre, Bichat University Hospital, Paris, France; 2 INSERM U-698 and Paris-Diderot University; and
Department of Radiology, Bichat University Hospital, Paris, France.
背景および目的：再開通は動脈閉塞患者における脳卒中転
帰の強力な予測因子である。組換え型組織プラスミノゲン
活性化因子の静脈内投与は再開通率に限界があるが，こ
れは機械的血管内治療（ MET ）で改善される可能性がある。
しかし，MET の有益性と安全性はまだ明確にされていな
い。本研究の目的は，MET の有効性および安全性の信頼
できる推定値を示すことである。
方法：当施設の前向き臨床登録のデータを分析し，1966
年 1 月から 2009 年 11 月までに発表された MET を用いた
過去の全研究の系統的レビューを行った。
結果：2007 年 4 月から 2009 年 11 月までに，ビシャ病院で
急性脳卒中の患者 47 例が MET による治療を受けた。文
献検索で，合計 1,066 例の被験者を対象とした 31 件の過
去の研究が同定された。当施設の登録データを含めたメタ
解析では，全体的な再開通率は 79％（ 95％ CI：73 ～ 84 ）
であった。臨床転帰のメタ解析で得られた統合推定値は，
良好な転帰については 40％（ 95％ CI：34 ～ 46，27 件の
研究）
，死亡率については 28％（ 95％ CI：23 ～ 33，28 件
の研究）
，症候性頭蓋内出血については 8％（ 95％ CI：6
～ 10，27 件の研究）であった。良好な転帰の可能性は血
栓溶解療法の使用とともに上昇し（ OR ＝ 1.99，95％ CI：
1.23 ～ 3.22 ）
，また中大脳動脈単独閉塞患者の割合ととも
に上昇した（ 10％増加ごとの OR ＝ 1.14，95％ CI：1.04
～ 1.25 ）
。
結論：MET は脳卒中患者において許容可能な安全性およ
び有効性を有しており，中大脳動脈単独閉塞を呈する患者
においては治療選択肢となる可能性がある。
Stroke 2011; 42: 1289-1294
表
再開通および臨床転帰の統合した割合
転帰
研究数
患者数
統合割合，％（95％ CI）
p 値*
I 2，％
32
1113
78.6 (72.9 〜 83.7)
＜ 0.0001
77.5
主解析
部分的または完全な再開通
完全な再開通
24
580
41.4 (32.1 〜 51.0)
＜ 0.0001
80.6
良好な転帰
27
961
39.9 (34.0 〜 45.9)
＜ 0.0001
66.8
死亡率
28
952
27.5 (22.7 〜 32.6)
＜ 0.0001
59.7
出血性合併症
25
919
27.2 (21.9 〜 32.8)
＜ 0.0001
65.9
症候性頭蓋内出血
27
983
8.1 (6.2 〜 10.4)
0.15
22.0
感度解析†
良好な転帰
23
877
40.6 (34.4 〜 46.9)
＜ 0.0001
66.4
死亡率
22
806
28.3 (23.1 〜 33.8)
0.0009
56.4
出血性合併症
21
823
28.9 (23.4 〜 34.7)
＜ 0.0001
62.7
症候性頭蓋内出血
14
685
9.1 (6.6 〜 11.9)
0.22
21.4
CI：信頼区間。
* 不均一性に関する χ2 検定に関連した p 値。
†
当施設の定義に近い転帰を用いた研究に限定。
stroke6-2.indb 30
11.9.27 10:54:02 AM
Artículos originales
Resultados del tratamiento endovascular mecánico
para el ictus agudo
Un estudio de registro clínico y revisión sistemática
Jean-Michel Serfaty, MD; Jean-Pierre Laissy, MD; Philippa C. Lavallée, MD; Lucie Cabrejo, MD;
Céline Guidoux, MD; Bertrand Lapergue, MD; Isabelle F. Klein, MD, PhD;
Jean-Marc Olivot, MD, PhD; Halim Abboud, MD; Olivier Simon, MD, PhD;
Elisabeth Schouman-Claeys, MD; Pierre Amarenco, MD
Antecedentes y objetivo—La recanalización es un predictor potente de la evolución clínica del ictus en pacientes con oclusión arterial. El empleo intravenoso del activador de plasminógeno tisular recombinante se ve limitado por su tasa de
recanalización, que puede mejorarse con el tratamiento endovascular mecánico (TEM). Sin embargo, no se han determinado aún el efecto beneficioso y la seguridad del TEM. El objetivo de este estudio fue aportar estimaciones fiables de
los resultados de eficacia y seguridad del TEM.
Métodos—Hemos analizado los datos de nuestro registro clínico prospectivo y hemos realizado una revisión sistemática de
todos los estudios previos del uso del TEM publicados entre enero de 1966 y noviembre de 2009.
Resultados—Entre abril de 2007 y noviembre de 2009, un total de 47 pacientes con ictus agudo fueron tratados con TEM
en el Hospital Bichat. La búsqueda bibliográfica identificó 31 estudios previos con un total de 1066 pacientes. En el
metanálisis, con la inclusión de los datos de nuestro registro, la tasa de recanalización global fue de un 79% (IC del 95%,
73–84). El metanálisis de los resultados clínicos aportó una estimación combinada del 40% (IC del 95%, 34–46; 27 estudios) para el resultado favorable, 28% (IC del 95%, 23–33; 28 estudios) para la mortalidad, y 8% (IC del 95%, 6–10;
27 estudios) para la hemorragia intracraneal sintomática. La probabilidad de un resultado favorable aumentaba con el
uso de trombolisis (OR, 1,99; IC del 95%, 1,23–3,22) y con la proporción de pacientes con una oclusión aislada de la
arteria cerebral media (OR por 10% de aumento, 1,14; IC del 95%, 1,04–1,25).
Conclusiones—El TEM se asocia a una seguridad y eficacia aceptables en los pacientes con ictus, y puede ser una opción
terapéutica en los pacientes que presentan una oclusión aislada de la arteria cerebral media. (Traducido del inglés:
Outcomes of Mechanical Endovascular Therapy for Acute Ischemic Stroke. A Clinical Registry Study and Systematic Review. Stroke. 2011;42:1289-1294.)
Palabras clave: alteplase Q endovascular therapy Q mechanical approach Q recombinant tissue plasminogen activator
Q stroke Q thrombectomy
L
periores en los pacientes con infarto cerebral que presentan
un patrón de oclusión arterial similar3. Estas tasas de recanalización pueden mejorarse hasta el 87% con un tratamiento endovascular mecánico (TEM)1,4. Aunque se ha descrito
la viabilidad del TEM en pacientes con infarto cerebral, su
seguridad continúa sin haber sido demostrada. En la actualidad disponemos de varios dispositivos, pero ninguno de
ellos ha sido evaluado mediante una comparación directa
a recanalización es un predictor potente de la evolución clínica del ictus en los pacientes con una oclusión
arterial tratados con activador de plasminógeno tisular recombinante (rt-PA) intravenoso (i.v.) o con un abordaje endovascular1. El rt-PA i.v. se ve limitado por su tasa de recanalización en el contexto de oclusiones de arterias grandes2,
mientras que el tratamiento trombolítico intraarterial puede
alcanzar unas tasas de recanalización significativamente su-
Recibido el 12 de septiembre de 2010; aceptado el 11 de noviembre de 2010.
Department of Neurology and Stroke Centre (A.R., M.M., E.M., P.C.L., L.C., C.G., B.L., J.M.O., O.S., H.A., P.A.), Bichat University Hospital, París,
Francia; INSERM U-698 y Paris-Diderot University (A.R., M.M., J.L., B.L., P.C.L., J.M.S., P.A.); y Department of Radiology (J.M.S., J.P.L., I.F.K.,
E.S.-C.), Bichat University Hospital, París, Francia.
El suplemento de datos de este artículo, disponible solamente online, puede consultarse en http://stroke.ahajournals.org/cgi/content/full/
STROKEAHA.110.599399/DC1.
Anthony J. Furlan,, MD, fue el editor invitado para este artículo.
Remitir la correspondencia a Mikael Mazighi, Department of Neurology and Stroke Centre, Bichat University Hospital, 46, rue Henri Huchard, 75018
Paris, Francia. Correo electrónico [email protected]
© 2011 American Heart Association, Inc.
Stroke está disponible en http://www.stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.110.599399
110
Rouchaud y cols. Resultados del tratamiento endovascular mecánico para el ictus agudo 111
Figura 1. Diagramas de flujo
del proceso de selección de
artículos para el estudio.
con el tratamiento de rt-PA i.v., que continúa siendo el tratamiento de referencia. Se están realizando ensayos controlados y aleatorizados, como el IMS-3, para comparar el
tratamiento i.v. con un enfoque que combina el tratamiento
i.v. con el abordaje endovascular. A la espera de los resultados de este ensayo, no existen recomendaciones para los
abordajes mecánicos en los pacientes con infarto cerebral,
y el TEM se continúa considerando una técnica de investigación. El objetivo de este estudio fue obtener estimaciones
fiables de los resultados de eficacia y seguridad del TEM en
pacientes con ictus. Así pues, hemos analizado los datos de
nuestro registro clínico prospectivo y hemos realizado una
revisión sistemática de todos los estudios previos del uso de
este abordaje endovascular.
Material y métodos
Programa de ictus Bichat
Se identificó a los pacientes a partir de un registro clínico
prospectivo de pacientes con ictus tratados entre febrero de
2002 y noviembre de 2009. Antes de abril de 2007, todos los
pacientes fueron tratados con rt-PA i.v. según el diseño del
National Institute of Neurological Disorders and Stroke5. La
edad no se consideró una contraindicación para el uso de rtPA i.v. A partir de abril de 2007, se aplicó un enfoque sistemático que incluía el TEM en los pacientes con una oclusión
arterial confirmada mediante angio-RM o angio-TC. En los
pacientes que acudían en un plazo de 3 horas tras el inicio
de los síntomas, se utilizó un TEM con tratamiento combinado con rt-PA i.v. e intraarterial (0,6 mg/kg i.v. y 0,3 mg/
kg intraarterial)1. En los pacientes ingresados después de las
3 horas, se utilizó rt-PA intraarterial y se consideró la posible
conveniencia de un TEM adyuvante si persistía la oclusión.
En los pacientes con una contraindicación para el uso de rtPA5, se contempló el uso directo de un abordaje de TEM.
No se utilizó ningún TEM después de transcurridas 6 horas
tras el inicio de los síntomas. Se presenta una información
adicional sobre la obtención de los datos y las definiciones en
el Suplemento (http://stroke.ahajournals.org).
Revisión sistemática
Identificamos todos los estudios observacionales y de intervención publicados entre enero de 1966 y noviembre de 2009
en los que se describía la recanalización y/o el resultado clínico en pacientes con un ictus consecutivo a una oclusión arterial tratados con TEM. Realizamos una búsqueda en la base
de datos MEDLINE con el empleo de los siguientes términos de búsqueda: “endovascular”, “mechanical”, “thrombectomy”, “clot removal”, “clot disruption in combination
with stroke”, “cerebrovascular disease” y “brain infarction”. Las búsquedas se limitaron a los estudios publicados
en inglés y realizados en el ser humano. Uno de los autores
(A.R.) se encargó de seleccionar los artículos de posible relevancia en función del título y el resumen, y de obtener el
texto completo para un examen detallado. Llevamos a cabo
también una búsqueda en los apartados de bibliografía de los
artículos obtenidos y de los artículos de revisión publicados,
para identificar otros estudios adicionales. La metodología
utilizada para la selección de los estudios y la extracción de
los datos se presenta en el Suplemento.
Análisis estadístico
X"#?""["""\*]?
de 0,05, excepto en las pruebas de homogeneidad, para las
^"_*]`{X"""\
con el programa informático SAS versión 9.1 (SAS Institute)
y con el paquete Cochrane Collaboration’s Review Manager
(RevMan edición 4·2·7). Se presenta una información adicional sobre el Registro Clínico Bichat y sobre el análisis de
revisión sistemática en el Suplemento.
112
Stroke
Noviembre 2011
Tabla. Tasas globales de recanalización y resultados clínicos
Número de
estudios
Número de
pacientes
Recanalización parcial o completa
32
1113
78,6 (72,9-83,7)
0,0001
77,5
Recanalización completa
24
580
41,4 (32,1-51,0)
0,0001
80,6
Resultado favorable
27
961
39,9 (34,0-45,9)
0,0001
66,8
Mortalidad
28
952
27,5 (22,7-32,6)
0,0001
59,7
Complicación hemorrágica
25
919
27,2 (21,9-32,8)
0,0001
65,9
Hemorragia intracraneal sintomática
27
983
8,1 (6,2-10,4)
0,15
22,0
Resultados
Tasas combinadas
(IC del 95%)
P*
I 2, %
Análisis principal
Análisis de sensibilidad†
Resultado favorable
23
877
40,6 (34,4-46,9)
0,0001
66,4
Mortalidad
22
806
28,3 (23,1-33,8)
0,0009
56,4
Complicación hemorrágica
21
823
28,9 (23,4-34,7)
0,0001
62,7
Hemorragia intracraneal sintomática
14
685
9,1 (6,6-11,9)
0,22
21,4
IC indica intervalo de confianza.
*p asociada a una prueba de χ2 para la heterogeneidad.
†Limitado a los estudios con un resultado más próximo a la definición de nuestro centro.
Resultados
Registro Clínico Bichat
Entre abril de 2007 y noviembre de 2009, un total de 47 pacientes con ictus agudo fueron tratados con TEM. El TEM se
utilizó como método de rescate en 37 pacientes y como abordaje directo en 10 pacientes. La mediana de tiempo transcurrido entre el inicio de los síntomas y el tratamiento fue
de 2,3 horas (rango, 1,1–6,1 horas) en los pacientes con un
TEM de rescate y de 4,9 horas (rango, 2,8–15,0 horas) en los
demás pacientes.
Las características basales, las tasas de recanalización y los
resultados clínicos, de forma global y según la indicación para el uso del TEM se presentan en la Tabla I del Suplemento
(http://stroke.ahajournals.org). Se alcanzó una recanalización
(Thrombolysis in Myocardial Infarction 2 ó 3) en el 81% de
los casos, sin que hubiera diferencias entre los 2 grupos. La
mediana de tiempo transcurrido entre el inicio de los síntomas y la recanalización fue de 4,0 horas (rango, 2,9–6,7 horas) en el grupo con un tratamiento de rescate y de 6,1 horas
(rango, 4,8–12,7 horas) en el grupo de tratamiento directo.
Excepto por una tendencia a una tasa de mejoría neurológica temprana inferior en el grupo de tratamiento directo, no
se observaron diferencias en los resultados clínicos. Globalmente, el 47% presentaron un resultado favorable (puntuación de mRS, 0–2) a los 90 días, el 19% fallecieron en un
plazo de 3 meses y el 40% sufrieron complicaciones hemorrágicas en las primeras 24 horas. Se produjo una hemorragia
intracraneal sintomática en 4 pacientes tratados con TEM de
rescate (11%) y en 1 paciente al que se aplicó el tratamiento
mecánico de primera línea (10%). En el análisis univariable
realizado para el conjunto de ambos grupos, los pacientes con
una oclusión aislada de la arteria cerebral media (ACM) presentaron con mayor frecuencia un resultado clínico a los 90
días favorable (62%) en comparación con los pacientes con
una oclusión de la arteria carótida interna (27%) o una oclusión de la circulación posterior (33%; p = 0,04). Tal como se
ha descrito anteriormente1, la tasa de resultados clínicos a 90
días favorables aumentó gradualmente con el grado del flujo
Thrombolysis in Myocardial Infarction tras la intervención
|}2 prueba exacta de la tendencia, p = 0,003).
Revisión sistemática
La búsqueda bibliográfica identificó 3.277 citas. Tras revisar
los títulos y los resúmenes, se seleccionaron 86 artículos que
se leyeron en su totalidad y 31 de ellos fueron considerados
elegibles para la inclusión (Figura 1). Las principales características metodológicas y los datos basales de los estudios
incluidos se presentan en la Tabla II del Suplemento (http://
stroke.ahajournals.org). En 2 de los estudios incluidos, solamente fue posible extraer información relativa a las tasas
de recanalización, ya que el objetivo principal era describir
el subgrupo de pacientes tratados con la implantación de
stents de forma adyuvante en 1 estudio6 y describir a todos
los pacientes a los que se aplicó un tratamiento endovascular
que incluía trombolisis en el segundo estudio7. Los estudios
incluidos, con un total de 1.066 pacientes (mediana del tamaño muestral, 20; rango, 10–164), se llevaron a cabo principalmente (~64% de los casos) en Norteamérica. Ocho de los
estudios fueron estudios piloto de un solo grupo, diseñados
para evaluar la seguridad y/o la eficacia de los dispositivos de
revascularización mecánica8–15. Los 23 estudios restantes correspondían a series de casos; la mayoría de ellos (n = 17) se
clasificaron como análisis de series de casos retrospectivas.
El TEM se utilizó como tratamiento directo en 14 estudios
(con un total de 448 casos), como método de rescate en 8
estudios (con 134 casos), y con ambos enfoques en los 9 estudios restantes (con 484 casos). De los 23 estudios en los
que se utilizó el TEM como tratamiento directo, 7 emplearon el TEM como tratamiento de primera línea en pacientes
que eran aptos para el uso de rt-PA i.v.12,14,16 –20. Tal como se
muestra en la Tabla II del Suplemento, se emplearon diversos
TEM diferentes. De los 31 estudios incluidos, 10 utilizaron
dispositivos de extracción del coágulo como método de TEM
Figura 2. Valores brutos de odds ratios para (A) recanalización, (B) resultado clínico favorable, y (C) mortalidad para los subgrupos
de oclusión aislada de la arteria cerebral media en los estudios observacionales individuales y combinados. Un estudio21 con datos de
resultados según la localización del coágulo vascular no pudo ser incluido en el metanálisis de los resultados de recanalización y mortalidad porque todos los pacientes alcanzaron la recanalización y ninguno falleció en los 90 días siguientes al tratamiento. OR indica
odds ratio; IC, intervalo de confianza; ACM, arteria cerebral media.
114
Stroke
Noviembre 2011
de primera elección y 17 utilizaron una fragmentación del
coágulo mediante dispositivos adaptados o mediante la manipulación con la guía. En los 4 estudios restantes, se utilizó un
TEM multimodal. Se utilizó una trombolisis adyuvante en 18
estudios (incluidos los 14 estudios que presentaron tan sólo
datos de una estrategia de tratamiento directo con TEM). La
tasa de trombolisis (antes y/o después del TEM) osciló entre
el 7% y el 100% en los diversos estudios. En los 28 estudios
en los que se dispuso de datos sobre la localización del coágulo, el vaso afectado más frecuente fue la ACM (56% de los
casos), seguido de la arteria carótida interna (30%) y la circulación posterior (14%). Los porcentajes de pacientes según
la localización del coágulo variaban en los diversos estudios,
y la mediana de puntuación de NIHSS al ingreso osciló entre
138 y 2419.
En la Tabla se muestran las estimaciones globales de la tasa de recanalización y de resultados clínicos. En la Tabla III
del suplemento se presentan los resultados obtenidos en los
diversos estudios analizados (http://stroke.ahajournals.org).
En el metanálisis, con la inclusión de los datos de nuestro
centro, la tasa global de recanalización (parcial o completa)
fue de un 78,6% (IC del 95%, 72,9–83,7). Al considerar tan
solo las tasas de recanalización completa (24 estudios), las
estimaciones se redujeron al 41,4% (IC del 95%, 32,1%–
51,0%). El metanálisis de los resultados clínicos aportó una
estimación global del 39,9% (IC del 95%, 34,0–45,9; 27 estudios) para el resultado favorable, 27,5% (IC del 95%, 22,7–
32,6; 28 estudios) para la mortalidad, y 8,1% (IC del 95%,
6,2%–10,4%; 27 estudios) para la hemorragia intracraneal
sintomática. Los análisis de sensibilidad produjeron unas estimaciones globales similares (Tabla). Se observó una gran
heterogeneidad de los distintos estudios, con independencia
de los resultados.
En los análisis de metarregresión univariados, las tasas
de recanalización y de complicaciones hemorrágicas no
estuvieron relacionadas con covariables predefinidas a nivel de estudio (p > 0,10 en todos los casos). En cambio, la
tasa de resultados favorables estuvo relacionada con el uso
sistemático de la trombolisis química (OR, 1,79; IC del
95%, 1,05–3,05; p = 0,034) y la tasa de oclusión aislada
de la ACM (OR por 10% de aumento, 1,12; IC del 95%,
1,01–1,24; p = 0,036), y la tasa de mortalidad estuvo relacionada con el uso de trombolisis (OR, 0,47; IC del 95%,
0,30–0,75; p = 0,002). En el análisis de metarregresión
multivariado, la OR de un resultado favorable fue de 1,99
(IC del 95%, 1,23–3,22) para el uso de trombolisis y de
1,14 (IC del 95%, 1,04–1,25) por 10% de aumento de la
tasa de oclusión aislada de la ACM. Además, tal como se
muestra en la Figura 2, los pacientes con una oclusión aislada de la ACM presentaron una tasa de resultados favorables más elevada y una tasa de mortalidad inferior a la de
las demás localizaciones del coágulo en el metanálisis, con
la inclusión de todos los estudios que presentaban datos de
resultados según la localización del coágulo vascular. No
observamos evidencia alguna de un sesgo de publicación y
de selección importante al examinar los gráficos de embudo de las proporciones transformadas de Freeman-Tukey
frente a su error estándar (Figura del Suplemento, http://
stroke.ahajournals.org).
Discusión
Esta revisión sistemática, que incluye los datos de nuestro
registro, sugiere un perfil de eficacia y seguridad favorable
del TEM en el manejo de los pacientes con ictus isquémico
agudo. El análisis de metarregresión multivariable identificó
situaciones específicas asociadas a un buen resultado clínico, incluido el uso de trombolisis i.v. y/o intraarterial con el
TEM (OR, 1,99; IC del 95%, 1,23–3,22) y la proporción de
pacientes con una oclusión aislada de la ACM (OR por 10%
de aumento de la tasa de oclusión aislada de la ACM, 1,14;
IC del 95%, 1,04–1,25).
Como se ha descrito anteriormente1,4, la recanalización es
un objetivo crucial a alcanzar. En el registro Bichat, la recanalización arterial se alcanzó en un 81% de los pacientes, con
unos resultados a 90 días favorables en el 47%. Al añadir los
datos de los 31 estudios previos identificados, se obtuvieron
unas estimaciones globales similares, a pesar de la heterogeneidad sustancial existente entre los estudios. En el metanálisis, la tasa de recanalización global fue del 79% (IC del 95%,
73–84), y la estimación global de los resultados clínicos favorables fue del 40% (IC del 95%, 34–46; 27 estudios). Estos
resultados refuerzan la capacidad del TEM de aumentar las
tasas de recanalización y de un posible buen resultado clínico. Este último punto se pone de relieve en los pacientes
que presentan una oclusión aislada de la ACM. En el registro
Bichat, el 62% de estos pacientes presentaron un resultado
clínico favorable a los 3 meses y una tasa de recanalización
del 84%. Es interesante señalar que el análisis de metarregresión mostró que el resultado favorable aumentaba en paralelo
con la proporción de pacientes con una oclusión aislada de
la ACM. Los pacientes con una oclusión aislada de la ACM
eran no sólo los que obtenían un mayor efecto beneficioso
del TEM, sino también la mayoría de los tratados.
El TEM puede utilizarse como abordaje terapéutico directo
(por ejemplo, en caso de contraindicación para el rt-PA) y también como método de rescate tras el fracaso del rt-PA i.v. y/o
intraarterial. En el registro Bichat, el TEM se utilizó predominantemente (79%) como método de rescate, mientras que en la
revisión sistemática el TEM se empleó por igual como estrategia de recanalización de rescate y como tratamiento de primera
línea. Ninguno de estos 2 enfoques (tratamiento de rescate o
tratamiento directo) mostró una superioridad en cuanto a las
tasas de recanalización o los resultados clínicos. En el caso de
la trombolisis concomitante (utilizada en el 62% de los pacientes en la revisión sistemática y en el 79% en el registro Bichat),
el análisis de metarregresión mostró que la tasa de resultados
favorables era mayor en los estudios con uso de trombolisis
(i.v. o intraarterial) que en los que no la utilizaban (OR bruta,
1,79; IC del 95%, 1,05–3,05; p = 0,03). Estos resultados concuerdan con los datos recientes de los ensayos MERCI y Multi
MERCI, en los que se observó una reducción de la mortalidad
y del tiempo hasta la recanalización con el empleo de TEM
en pacientes tratados con trombolisis i.v.22. El uso combinado
de rt-PA i.v. y tratamiento endovascular tal como se realiza
en nuestro centro es probablemente un factor importante para
explicar las tasas de recanalización más altas observadas y el
resultado favorable del registro Bichat en comparación con lo
observado en la revisión sistemática. Sin embargo, no tuvimos
acceso a los datos individuales de los estudios y no pudimos
diferenciar a los pacientes que recibieron rt-PA, por vía i.v. o
intraarterial, antes del TEM de los que no lo recibieron. Esto
constituye ciertamente una limitación para apreciar el impacto
que tiene la administración de rt-PA antes del TEM sobre los
resultados clínicos.
El uso de TEM no influyó negativamente en los resultados
clínicos. El metanálisis mostró una estimación combinada
del 28% (IC del 95%, 23–33; 28 estudios) para la mortalidad,
y del 8% (IC del 95%, 6–10; 27 estudios) para la hemorragia
intracraneal sintomática. El empleo de un dispositivo o tipo
de TEM específico (es decir, la fragmentación del coágulo o
la captura del trombo) no se asoció a una relación beneficioriesgo mejor o peor. En la revisión sistemática, se observó
una amplia heterogeneidad en el uso de dispositivos para el
TEM, lo cual explica probablemente la ausencia de toda diferencia significativa en los resultados clínicos. De hecho,
en los estudios analizados se identificaron más de 20 métodos de TEM (es decir, fragmentación del coágulo o captura del trombo, tratamiento trombolítico adyuvante, tipo de
dispositivo). Esta heterogeneidad en el uso de estos métodos
ilustra lo que ocurre en la práctica clínica diaria de los neurointervencionistas. Es posible que algunos estudios relevantes
no fueran tenidos en cuenta en nuestra revisión sistemática.
Sin embargo, es improbable que este posible sesgo de publicación distorsionara de manera notable nuestros resultados,
puesto que no observamos indicio alguno de tal sesgo al examinar los gráficos de embudo. Por último, el hecho de que no
se obtuvieran datos de factores que se ha descrito que influyen en los resultados clínicos (como el tiempo hasta la recanalización) constituye otra limitación. Tal como se ha indicado en publicaciones previas1,4, la recanalización se asocia a
buenos resultados clínicos, pero el tiempo transcurrido entre
el inicio de los síntomas y la recanalización es probablemente
un mejor predictor de la buena evolución clínica1,23.
El presente metanálisis incluyó principalmente presentaciones de casos comparativas y series de casos con datos no
aleatorizados; no se han realizado ensayos controlados y aleatorizados para evaluar los dispositivos utilizados en el TEM.
Aunque no se han completado ensayos controlados y aleatorizados, sí hay algunos actualmente en marcha, en los que se
compara el abordaje endovascular (incluidos el TEM) con el
patrón de referencia, o se realiza una comparación directa de
diferentes dispositivos de TEM. Los resultados de estos ensayos pueden verse afectados por el tiempo transcurrido entre
el tratamiento con rt-PA i.v. y la decisión de realizar un TEM
de rescate, puesto que el TEM de rescate sólo se utilizará en
casos de falta de recanalización tras el tratamiento con rt-PA
i.v. Dado que el tiempo hasta la recanalización es el predictor
más potente de un resultado favorable, cualquier retraso en la
recanalización va seguido de una disminución de la tasa de
resultados favorables a 90 días. El uso de un abordaje endovascular durante el tratamiento con rt-PA i.v. (es decir, realización de una punción femoral y navegación hasta el coágulo
intracraneal inmediatamente después del bolo i.v.) reduciría
el tiempo hasta la recanalización.
Conclusiones
Son buenos candidatos para el TEM los pacientes con una
oclusión aislada de la ACM y los pacientes tratados de ma-
nera combinada con una trombolisis. Estos elementos pueden considerarse criterios de inclusión en el diseño de futuros
ensayos controlados y aleatorizados para evaluar el TEM en
comparación con el rt-PA i.v. solo. A la espera de los resultados de estos ensayos, los datos que se presentan aquí respaldan el uso del TEM como alternativa terapéutica en pacientes
con ictus agudo.
Agradecimientos
M.M., J.M.O., y P.A. participaron en la concepción y diseño del
estudio. A.R., J.L., M.M., y P.A. analizaron e interpretaron los datos. M.M., J.M.S., E.M., P.L., L.C., C.G., B.L., I.F.K., J.M.O., O.S.,
H.A., y J.P.L. se encargaron del aporte de material de estudio o de
pacientes. M.M. y E.M. se encargaron de la obtención, combinación
y posesión de los datos brutos. J.L. se responsabilizó del análisis
estadístico. A.R., M.M., J.L., y P.A. se encargaron de redactar el
borrador del artículo. E.S.C. y P.A. realizaron una revisión crítica
del manuscrito y aportaron contenido intelectual importante. P.A. se
responsabilizó de la aprobación final del artículo para publicación
y de la obtención de financiación para el estudio. Sophie RushtonSmith, PhD, aportó ayuda editorial en la versión final del manuscrito, incluida la corrección, verificación del contenido e idioma, y el
formateo del mismo.
Fuentes de financiación
La labor de Sophie Rushton-Smith fue financiada por SOS Attaque
Cérébrale.
Declaración de intereses
Ninguno.
Bibliografía
1. Mazighi M, Serfaty JM, Labreuche J, Laissy JP, Meseguer E, Lavallée
PC, Cabrejo L, Slaoui T, Guidoux C, Lapergue B, Klein IF, Olivot JM,
Abboud H, Simon O, Niclot P, Nifle C, Touboul PJ, Raphaeli G, Gohin
C, Claeys ES, Amarenco P, RECANALISE investigators. Comparison of
intravenous alteplase with a combined intravenous-endovascular
approach in patients with stroke and confirmed arterial occlusion
(RECANALISE study): a prospective cohort study. Lancet Neurol. 2009;
8:802– 809.
2. del Zoppo GJ, Poeck K, Pessin MS, Wolpert SM, Furlan AJ, Ferbert A,
Alberts MJ, Zivin JA, Wechsler L, Busse O. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol.
1992;32:78 – 86.
3. Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin
M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F. Intra-arterial
prourokinase for acute ischemic stroke. The PROACT II study: A randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism.
JAMA. 1999;282:2003–2011.
4. Rha JH, Saver JL. The impact of recanalization on ischemic stroke
outcome: a meta-analysis. Stroke. 2007;38:967–973.
5. 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.
6. Sauvageau E, Samuelson RM, Levy EI, Jeziorski AM, Mehta RA,
Hopkins LN. Middle cerebral artery stenting for acute ischemic stroke
after unsuccessful Merci retrieval. Neurosurgery. 2007;60:701–706.
7. Prabhakaran S, Chen M, Choi JH, Mangla S, Lavine SD, Pile-Spellman
J, Meyers PM, Chong JY. Major neurologic improvement following
endovascular recanalization therapy for acute ischemic stroke. Cerebrovasc Dis. 2008;25:401– 407.
8. Levy EI, Siddiqui AH, Crumlish A, Snyder KV, Hauck EF, Fiorella DJ,
Hopkins LN, Mocco J. First Food and Drug Administration-approved
prospective trial of primary intracranial stenting for acute stroke: SARIS
(stent-assisted recanalization in acute ischemic stroke). Stroke. 2009;40:
3552–3556.
116
Stroke
Noviembre 2011
9. Penumbra Pivotal Stroke Trial Investigators. 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.
10. Bose A, Henkes H, Alfke K, Reith W, Mayer TE, Berlis A, Branca V, Sit
SP, Penumbra Phase 1 Stroke Trial Investigators. The Penumbra System:
a mechanical device for the treatment of acute stroke due to thromboembolism. AJNR Am J Neuroradiol. 2008;29:1409 –1413.
11. Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS,
Lutsep HL, Rymer MM, Higashida RT, Starkman S, Gobin YP, Multi
MERCI Investigators, Frei D, Grobelny T, Hellinger F, Huddle D,
Kidwell C, Koroshetz W, Marks M, Nesbit G, Silverman IE. Mechanical
thrombectomy for acute ischemic stroke: final results of the Multi
MERCI trial. Stroke. 2008;39:1205–1212.
12. Mayer TE, Hamann GF, Schulte-Altedorneburg G, Brückmann H.
Treatment of vertebrobasilar occlusion by using a coronary waterjet
thrombectomy device: a pilot study. AJNR Am J Neuroradiol. 2005;26:
1389 –1394.
13. Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP, Lutsep
HL, Nesbit GM, Grobelny T, Rymer MM, Silverman IE, Higashida RT,
Budzik RF, Marks MP; MERCI Trial Investigators. Safety and efficacy of
mechanical embolectomy in acute ischemic stroke: results of the MERCI
trial. Stroke. 2005;36:1432–1438.
14. Berlis A, Lutsep H, Barnwell S, Norbash A, Wechsler L, Jungreis CA,
Woolfenden A, Redekop G, Hartmann M, Schumacher M. Mechanical
thrombolysis in acute ischemic stroke with endovascular photoacoustic
recanalization. Stroke. 2004;35:1112–1116.
15. Mahon BR, Nesbit GM, Barnwell SL, Clark W, Marotta TR, Weill A,
Teal PA, Qureshi AI. North American clinical experience with the EKOS
MicroLysUS infusion catheter for the treatment of embolic stroke. AJNR
Am J Neuroradiol. 2003;24:534 –538.
16. Devlin TG, Baxter BW, Feintuch TA, Desbiens NA. The Merci Retrieval
System for acute stroke: the Southeast Regional Stroke Center experience. Neurocrit Care. 2007;6:11–21.
17. Bergui M, Stura G, Daniele D, Cerrato P, Berardino M, Bradac GB.
Mechanical thrombolysis in ischemic stroke attributable to basilar artery
occlusion as first-line treatment. Stroke. 2006;37:145–150.
18. Imai K, Mori T, Izumoto H, Takabatake N, Kunieda T, Shimizu H,
Watanabe M. Clot removal therapy by aspiration and extraction for acute
embolic carotid occlusion. AJNR Am J Neuroradiol. 2006;27:1521–1527.
19. Sorimachi T, Fujii Y, Tsuchiya N, Nashimoto T, Harada A, Ito Y, Tanaka
R. Recanalization by mechanical embolus disruption during intra-arterial
thrombolysis in the carotid territory. AJNR Am J Neuroradiol. 2004;25:
1391–1402.
20. Nakano S, Iseda T, Yoneyama T, Kawano H, Wakisaka S. Direct percutaneous transluminal angioplasty for acute middle cerebral artery trunk
occlusion: an alternative option to intra-arterial thrombolysis. Stroke.
2002;33:2872–2876.
21. Barnwell SL, Clark WM, Nguyen TT, O’Neill OR, Wynn ML, Coull BM.
Safety and efficacy of delayed intraarterial urokinase therapy with
mechanical clot disruption for thromboembolic stroke. AJNR Am J Neuroradiol. 1994;15:1817–1822.
22. Shi ZS, Loh Y, Walker G, Duckwiler GR, MERCI and Multi MERCI
Investigators. Endovascular thrombectomy for acute ischemic stroke in
failed intravenous tissue plasminogen activator versus non-intravenous
tissue plasminogen activator patients: revascularization and outcomes
stratified by the site of arterial occlusions. Stroke. 2010;41:1185–1192.
23. Khatri P, Abruzzo T, Yeatts SD, Nichols C, Broderick JP, Tomsick TA,
IMS I and II Investigators. Good clinical outcome after ischemic stroke
with successful revascularization is time-dependent. Neurology. 2009;73:
1066 –1072.
Abstract
急性缺血性脑血管病的血管内机械治疗结果
一项临床登记研究及系统回顾
Outcomes of Mechanical Endovascular Therapy for Acute Ischemic Stroke
A Clinical Registry Study and Systematic Review
Jean-Michel Serfaty, MD; Jean-Pierre Laissy, MD; Philippa C. Lavallée, MD; Lucie Cabrejo, MD;
Céline Guidoux, MD; Bertrand Lapergue, MD; Isabelle F. Klein, MD, PhD; Jean-Marc Olivot, MD, PhD;
Halim Abboud, MD; Olivier Simon, MD, PhD; Elisabeth Schouman-Claeys, MD; Pierre Amarenco, MD
背景及目的：对于动脉闭塞的患者来说，血管再通术是中风后最有力的措施。静脉重组组织型纤溶酶原激活物使血管再
通的能力有限，机械式血管腔内疗法 ( 简称 MET) 可使血管再通率得到提高。但是，MET 疗法的有效性及安全性还有待
确定。本文旨在对 MET 疗法的有效性及安全性进行评估。
方法：我们对登记处的数据进行了分析，并对 1966 年 1 月至 2009 年 11 月进行 MET 疗法的病例进行了系统的总结。
结果：从 2007 年 4 月至 2009 年 11 月，47 位急性脑卒中患者在 BICHAT 医院接受了 MET 治疗。文献检索有 31 项之前
的研究报道，涉及 1066 个方面 ( 学科 )。在荟萃分析结果中 ( 包括本研究登记处的数据 )，再通率为 79% (95% CI, 7384)。临床结果的荟萃分析显示，积极疗效约占 40%，死亡占 28%，症状性颅内出血占 8%。积极效果与溶栓治疗及孤立
的大脑中动脉闭塞有关。
结论：MET 疗法对卒中患者来说安全有效，可能成为孤立性大脑中动脉闭塞患者积极的治疗方法。
关键词：阿替普酶；血管内疗法；机械方法；重组组织型纤溶酶原激活物；卒中；血栓
(Stroke. 2011;42:1289-1294.　吉林大学第一医院神经内科　孙莉译　杨弋吴江校 )
61

Outcomes of Mechanical Endovascular Therapy for Acute

Transcripción

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