Ischemic stroke Original research Benefit of endovascular thrombectomy for M2 middle cerebral artery occlusion in the ARISE II study Adam de Havenon ‍ ‍,1 Ana Paula Narata,2 Aymeric Amelot,3,4 Jeffrey L Saver,5 Hormozd Bozorgchami,6 Heinrich Paul Mattle,7 Marc Ribo,8,9 Tommy Andersson,10,11 Osama O Zaidat,12 On behalf of ARISE II investigators ►► Additional material is ABSTRACT studies and meta-­analyses have been published, all published online only. To view Background The benefit of endovascular of which show benefit for EVT.2–6 A meta-­analysis please visit the journal online (http://​dx.​doi.​org/​10.​1136/​thrombectomy for acute ischemic stroke with M2 of the Highly Effective Reperfusion evaluated in neurintsurg-​2020-​016427). segment middle cerebral artery occlusion remains Multiple Endovascular Stroke (HERMES) trials controversial, with uncertainty and paucity of data database, which included pooled data from several For numbered affiliations see specific to this population. of the landmark EVT trials, showed that patients end of article. with AIS with M2 occlusion who received EVT had Objective To compare outcomes between M1 and M2 occlusions in the Analysis of Revascularization in significantly better 90-­day outcomes than patients Correspondence to Dr Osama O Zaidat, Mercy Ischemic Stroke with EmboTrap (ARISE II) trial. with an M2 occlusion who did not undergo EVT.7 Health St Vincent Medical Methods We performed a prespecified analysis of The Analysis of Revascularization in Ischemic Center, Toledo, OH 43608, USA; ​ the ARISE II trial with the primary outcome of 90-­day Stroke with EmboTrap (ARISE II) trial reported that ozaidat@​hotmail.​com modified Rankin Scale score of 0–2, which we termed the EmboTrap revascularization device achieved good outcome. Secondary outcomes included reperfusion high rates of successful reperfusion and good func- AdH and APN are joint first authors. rates and major adverse events. The primary predictor tional outcome with minimal adverse events.8 A was M2 occlusion, which we compared with M1 quarter of the patients enrolled in ARISE II had Received 26 May 2020 occlusion. M2 occlusion, which was permissible in the trial Revised 4 September 2020 Results We included 183 patients, of whom 126 (69%) because the 0.021” microcatheter compatibility Accepted 6 September 2020 Published Online First had M1 occlusion and 57 (31%) had M2 occlusion. There of EmboTrap allowed entry into the M2 segment. 20 November 2020 was no difference in the reperfusion rates or adverse Given the ongoing uncertainty about the efficacy events between M2 and M1 occlusions. The rate of good of EVT for M2 occlusions and lack of data specific outcome was not different in M2 versus M1 occlusions to EmboTrap in this population, we performed a (70.2% vs 69.7%, p=0.946). In a logistic regression subgroup analysis of ARISE II to compare rates of model adjusted for age, sex, and baseline National successful reperfusion, adverse events, and good Institutes of Health Stroke Scale score, M2 occlusions did outcome between M1 and M2 occlusions. not have a significantly different odds of good outcome compared with M1 occlusions (OR 0.94, 95% CI 0.47 to METHODS 1.88, p=0.87). Cohort Conclusion In ARISE II, M2 occlusions achieved a We performed a prespecified analysis of the ARISE 70.2% rate of good outcome at 90 days, which is II trial, an open-­ label, single-­ arm, multicenter, above published rates for untreated M2 occlusions and prospective clinical study designed to evaluate superior to prior reports of M2 occlusions treated with the safety and efficacy of the EmboTrap device in endovascular thrombectomy. We also report similar rates patients with AIS compared with efficacy rates for of good outcome, successful reperfusion, death, and two FDA-­ approved stent retriever devices.8 The other adverse events when comparing the M1 and M2 data for this analysis were de-­identified, which did occlusions. not require institutional review board approval. All data relevant to the study are included in the article or uploaded as online supplemental information. The EmboTrap revascularization device (Neuravi/ INTRODUCTION Cerenovus, Galway, Ireland) is a dual-­layer stent The benefit of endovascular thrombectomy (EVT) retriever, engineered with articulating petals, for acute ischemic stroke (AIS) caused by M2 and a distal capture zone for effectively trapping, segment middle cerebral artery (MCA) occlusion retaining, and removing large vessel occlusive © Author(s) (or their has not been evaluated in a randomized controlled clots causing AIS. Key ARISE II inclusion criteria employer(s)) 2021. Re-­use permitted under CC BY-­NC. No trial specific to that population. The natural history included pre-­stroke modified Rankin Scale (mRS) commercial re-­use. See rights of an untreated M2 occlusion, although not as score ≤1, baseline National Institutes of Health and permissions. Published ominous as an untreated M1 segment or internal Stroke Scale (NIHSS) score ≥8 and ≤25, Alberta by BMJ. carotid artery occlusion, is nonetheless poor. Fewer Stroke Program Early CT Score (ASPECTS) ≥6 or To cite: de Havenon A, than half of patients achieve functional indepen- core infarct volume <50 mL on MRI or CT-­based Narata AP, Amelot A, et al. dence by 90 days.1 A small number of patients imaging (for anterior circulation strokes), and treat- J NeuroIntervent Surg with AIS with M2 occlusion were included in the ment with intravenous tissue-­ type plasminogen 2021;13:779–783. landmark EVT trials, and multiple retrospective activator, if eligible, within 3 hours of stroke onset. de Havenon A, et al. J NeuroIntervent Surg 2021;13:779–783. doi:10.1136/neurintsurg-2020-016427 1 of 6 Ischemic stroke For our analysis, we included ARISE II patients with angiograph- or a Satterthwaite approximation in cases of unequal variances ically confirmed M1 and M2 MCA occlusion and excluded those as appropriate for continuous variables. We fitted multivariate with posterior circulation or internal carotid artery occlusion. logistic regression models with covariates that were chosen from patient age (reference <75 years), sex (reference female), NIHSS Outcomes and predictors score at admission, and time from symptom onset or last known The primary outcome of our analysis was good functional well to arterial puncture using least absolute shrinkage and selec- outcome defined as an mRS score of 0–2 at 90 days from stroke tion operator variable selection. onset. The secondary outcomes included: (1) successful reper- fusion, defined as modified thrombolysis in cerebral infarction RESULTS (mTICI) score ≥2 b, ≥2c, and 3 after the first pass, last of up to The ARISE II study enrolled 244 patients, of which we included three passes (ARISE II primary endpoint), and final pass; (2) the 183 (see figure 1). In our cohort, 126 (69%) had M1 occlu- ordinal categories of the mRS; (3) good outcome defined as mRS sion and 57 (31%) had M2 occlusion. Baseline demographics score 0–1 at 90 days; and (4) major adverse events, including are shown in table 1. The patients with an M2 occlusion were death within 90 days, symptomatic intracranial hemorrhage, and significantly older than M1 occlusion patients (71.2 vs 66.9 procedure-­related serious adverse events. The imaging core labo- years, p=0.033) and had a lower mean NIHSS score (14.4 vs ratory defined mTICI for M2 occlusions based on the percentage 15.9, p=0.051). reperfusion of the territory supplied by the occluded M2. For categorical variables, p values are generated using a χ2 The primary predictor is M2 occlusion, which we compared test or a Fisher’s exact test (due to expected cell sizes <5), as with M1 occlusion because of its similarity in phenotype and appropriate. procedural approach. We also analyzed our outcomes by the There was no difference in the imaging core laboratory following imaging core laboratory adjudicated stratifications: adjudicated reperfusion rates between M1 and M2 occlusions dominant versus non-­dominant M2 and proximal versus distal (online supplemental table 1). The rates of mTICI score ≥2c M2 origin. The following definitions were applied: dominant at the first pass, last of up to three passes, and final pass were M2 (supplying ≥50% of the MCA territory), non-­dominant M2 38.6%, 64.9%, and 73.7% for M2 occlusions. These rates did (supplying <50% of the MCA territory), proximal M2 (assessed not differ compared with M1 occlusions (all p values ≥0.7). We on coronal images; origin proximal to the mid-­sylvian point), did observe a higher percentage of mTICI scores of 3 after the and distal M2 (origin distal to the mid-­sylvian point).7 final pass for M2 occlusion than for M1 occlusion (56.1% vs 46.8%, p=0.243), but it did not reach statistical significance. Statistical analysis All serious procedure-­ related adverse events are shown in Categorical data are presented as proportions, normally distrib- table 2. The rates of serious adverse events adjudicated by the uted continuous data as mean with SD, and ordinal data as ARISE-­ II Clinical Events Committee, including procedure-­ median with IQR. Subject characteristics at enrollment were related complications, procedure-­related mortality, and symp- summarized by the full cohort and the subgroups of M1 versus tomatic intracranial hemorrhage within 24 hours of stroke onset, M2 occlusion. We tested for intergroup differences in the M1/2 were not significantly different between M1 and M2 occlusions occlusion subgroups, M2 stratifications, and in our primary and (table 2). Additional adverse events, including adjudication secondary outcomes with the χ2 test or Fisher’s exact test (due of relatedness to the study intervention, are shown in online to expected cell sizes <5) as appropriate for binary variables, the supplemental table 2, including the Heidelberg Bleeding Clas- Wilcoxon rank-­sum test for ordinal variables, and Student’s t-­test sification of postprocedural hemorrhage.9 No serious adverse Figure 1 Study flow chart showing the derivation of our cohort. 2 of 6 de Havenon A, et al. J NeuroIntervent Surg 2021;13:779–783. doi:10.1136/neurintsurg-2020-016427 Ischemic stroke Table 1 Baseline demographic data for the full cohort (n=183), and after stratification by M1 (n=126) and M2 (n=57) middle cerebral artery (MCA) occlusions All subjects MCA M1 MCA M2 Demographic data (n=183) (n=126) (n=57) P value Age at enrollment, years  Mean (SD) 68.2 (12.9) 66.9 (13.1) 71.2 (12.0) 0.0330  Median 70 69 75  Min to max 20 to 86 23 to 85 20 to 86  ≥75, N (%) 74 (40.4) 45 (35.7) 29 (50.9) 0.0529  <75, N (%) 109 (59.6) 81 (64.3) 28 (49.1) Sex, N (%)  Male 87 (47.5) 57 (45.2) 30 (52.6) 0.3537  Female 96 (52.5) 69 (54.8) 27 (47.4) NIHSS score at presentation  Mean (SD) 15.42 (4.42) 15.90 (4.41) 14.37 (4.31) 0.0507  Median 16 16 14  Q1 to Q3 12 to 19 12 to 19 12 to 18  Min to max 7 to 26 8 to 26 7 to 23 Baseline ASPECTS  N 168 117 51  Mean (SD) 9.38 (1.16) 9.38 (1.22) 9.37 (1.00) 0.3723  Median 10.00 10.00 10.00  Q1 to Q3 9.00 to 10.00 9.00 to 10.00 9.00 to 10.00  Min to max 4.00 to 10.00 4.00 to 10.00 5.00 to 10.00 Pre-­stroke mRS score, N (%)  0 139 (76.0) 96 (76.2) 43 (75.4) 0.8983  1 43 (23.5) 29 (23.0) 14 (24.6)  2 1 (0.5) 1 (0.8) 0 Occlusion side, left, N (%) 87 (47.5) 57 (45.2) 30 (52.6) 0.3537 Symptom onset or LKW to arterial puncture, min  N 140 95 45  Mean (SD) 201.59 (77.28) 198.72 (76.26) 207.64 (79.93) 0.5251  Median 195 187 214 Hypertension, N (%) 127 (69.4) 85 (67.5) 42 (73.7) 0.3975 Diabetes mellitus, N (%) 37 (20.2) 25 (19.8) 12 (21.1) 0.8501 Atrial fibrillation, N (%) 72 (39.3) 47 (37.3) 25 (43.9) 0.4003 Hyperlipidemia, N (%) 80 (43.7) 50 (39.7) 30 (52.6) 0.1020 Smoking, N (%) 48 (26.2) 36 (28.6) 12 (21.1) 0.2843 Previous MI/CAD, N (%) 39 (21.3) 30 (23.8) 9 (15.8) 0.2199 Previous stroke, N (%) 33 (18.0) 21 (16.7) 12 (21.1) 0.4748 Intravenous tPA failure, N (%) 123 (67.2) 85 (67.5) 38 (66.7) 0.9157 For continuous variables, p values are generated using a t-­test, with a Satterthwaite approximation in cases of unequal variances. For ordinal variables (NIHSS score at presentation, baseline ASPECTS), p values are generated using the Wilcoxon rank-­sum test. ASPECTS, baseline Alberta Stroke Program Early CT score; CAD, coronary artery disease; IA, intra-­arterial; IV, intravenous; LKW, last known well; MCA, middle cerebral artery; MI, myocardial; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale/Score; tPA, tissue plasminogen activator. events adjudicated by the Clinical Events Committee were found balanced (table 3), as was the percentage with a 90-­day mRS of to be related to the EmboTrap device. 0–1 (M2 vs M1 occlusion, 57.9% vs 54.9%, p=0.709). A 90-­day mRS score was available in 179/183 patients in our In a multivariate logistic regression model adjusted for age, cohort. Good outcome (mRS score 0–2) was present in 125/179 sex, and NIHSS, M2 occlusion did not have an association (69.8%) of patients, and the rate was not different in M2 vs with good outcome (OR 0.94, 95% CI 0.47 to 1.88, p=0.87). M1 occlusion (70.2% vs 69.7%, p=0.946). The percentage of In a multivariate logistic regression model adjusted for age and patients in the individual categories of the 90 day mRS score was NIHSS, M2 occlusion also did not have an association with de Havenon A, et al. J NeuroIntervent Surg 2021;13:779–783. doi:10.1136/neurintsurg-2020-016427 3 of 6 Ischemic stroke Table 2 Serious procedure-­related adverse events as determined by Table 3 Modified Rankin Scale (mRS) scores at 90 days, which were the Clinical Events Committee available in 122 patients with M1 and 57 patients with M2 middle MCA M1 MCA M2 cerebral artery (MCA) occlusions Adverse events (n=126) (n=57) P value* MCA M1 MCA M2 Procedure-­related serious adverse 4 (3.2%) 5 (8.8%) 0.1396 (n=122) (n=57) P value* events Good outcome (90 day mRS score 0–2), 85 (69.7) 40 (70.2) 0.9455 Postprocedural subarachnoid 2 (1.6%) 2 (3.5%) 0.5896 n (%) hemorrhage 90-­Day mRS score, n (%) Vessel perforation 2 (1.6%) 0 (0%) 1.0000  0 37 (30.3) 16 (28.1) 0.9358 Carotid artery dissection 0 (0%) 1 (1.8%) 0.3115  1 30 (24.6) 17 (29.8) Cerebral artery occlusion 0 (0%) 1 (1.8%) 0.3115  2 18 (14.8) 7 (12.3) Ischemic stroke (iatrogenic) 1 (0.8%) 0 (0%) 1.0000  3 9 (7.4) 4 (7.0) Neurological decompensation 0 (0%) 1 (1.8%) 0.3115  4 15 (12.3) 5 (8.8) Vessel puncture site hemorrhage 0 (0%) 1 (1.8%) 0.3115  5 5 (4.1) 2 (3.5) Vessel puncture site thrombosis 0 (0%) 1 (1.8%) 0.3115  6 8 (6.6) 6 (10.5) Symptomatic intracranial hemorrhage 6 (4.8%) 2 (3.5%) 1.0000 90-­Day mRS score 0–1, n (%) 67 (54.9) 33 (57.9) 0.7087 within 24 hours *For categorical variables, p-­values are generated using a χ2 test or a Fisher’s exact Procedure-­related mortality 0 0 – test (due to expected cell sizes<5) as appropriate. (at 7 days postprocedure) *For categorical variables, p values are generated using a χ2 test or a Fisher’s exact test (due to expected cell sizes <5), as appropriate. can cause significant morbidity, and the expansion of EVT to this MCA, middle cerebral artery. patient population could improve stroke outcomes.17 Compared with patients with AIS with untreated M2 occlusion, EVT with the EmboTrap device almost doubled the percentage of mRS score 0–1 (OR 0.92, 95% CI 0.43 to 1.96, p=0.83) or all-­ patients who achieve a good outcome (70.2%). In the HERMES cause mortality (OR 1.43, 95% CI 0.43 to 4.70, p=0.56) (online database there were 62 patients with untreated M2 occlusion, supplemental table 3). derived from control arms of clinical trials.7 Those patients had There were 33/57 (57.9%) patients with a dominant M2 versus a 39.7% rate of good outcome at 90 days. A multicenter retro- 24/57 (42.1%) with a non-­dominant M2, and 27/57 (47.4%) spective study by Sarraj et al had 234 patients with untreated M2 with a proximal M2 origin versus 30/57 (52.6%) with a distal occlusion, who had a 35.4% rate of good outcome at 90 days.3 In M2 origin. The angiographic and functional outcomes were not a final study of the RESUCE-­Japan Registry 2 cohort, there were significantly different in these M2 stratifications (table 4). 188 untreated M2 occlusions, who had a higher 50.5% rate of good outcome at 90 days.18 Compared with previously reported DISCUSSION data, the outcomes for patients with M2 occlusion with AIS treated The rate of good functional outcome, successful reperfusion, with EVT in ARISE II were excellent. For example, in ARISE II, and adverse events did not differ significantly between M1 and good outcome (mRS score 0–2) at 90 days was seen in 70.2% M2 occlusions in patients with AIS treated with the EmboTrap of M2 occlusions. In the HERMES, Sarraj, and RESCUE-­Japan device in ARISE II. Among the 833 patients randomized to EVT studies, M2 occlusion treated with EVT achieved a rate of good in the seven major EVT trials published since 2015 (MR CLEAN, outcome of 58.2%, 62.8%, and 57.1%, respectively. In two meta-­ ESCAPE, EXTEND-­ IA, SWIFT PRIME, REVASCAT, DAWN, analyses comparing EVT in M1 versus M2 occlusions,5 6 the rate DEFUSE 3), only 55 patients had an M2 occlusion.10–16 In ARISE of good outcome for M2 occlusions was 59%. All these studies II, we enrolled 57 patients with M2 occlusion, which represents a also reported the safety of EVT for M2 occlusions, similar to the larger sample size. Accordingly, these results are important given data we report. the rigor of outcome adjudication in ARISE II and the lack of data Both meta-­analyses reported that EVT-­treated patients with specific to the EmboTrap device. Prior studies have established that AIS with an M2 occlusion had better outcomes than patients the M2 segment is a common site of large vessel occlusion that with an M1 occlusion.5 6 In ARISE II, we found no difference in Table 4 Primary outcomes in stratifications of patients with M2 occlusions, including dominant versus non-­dominant M2 and proximal versus distal M2 origin Dominant Non-­Dominant Proximal Distal Outcome (n=33) (n=24) P value* (n=27) (n=30) P value* Good outcome (90 day mRS score 0–2) 22 (66.7%) 18 (75.0%) 0.4971 17 (63.0%) 23 (76.7%) 0.2588 90-­Day mRS 0–1 20 (60.6%) 13 (54.2%) 0.6269 14 (51.9%) 19 (63.3%) 0.3807 All-­cause mortality at 90 days 2 (6.1%) 4 (16.7%) 0.2275 3 (11.1%) 3 (10.0%) 1.0000 Final pass mTICI ≥2b 30 (90.9%) 22 (91.7%) 1.0000 25 (92.6%) 27 (90.0%) 1.0000 Final pass mTICI ≥2c 24 (72.7%) 18 (75.0%) 0.8474 18 (66.7%) 24 (80.0%) 0.2537 Final pass mTICI 3 16 (48.5%) 16 (66.7%) 0.1720 16 (59.3%) 16 (53.3%) 0.6526 *For categorical variables, p values are generated using a χ2 test or a Fisher’s exact test (due to expected cell sizes<5) as appropriate. mTICI, modified thrombolysis in cerebral infarction . 4 of 6 de Havenon A, et al. J NeuroIntervent Surg 2021;13:779–783. doi:10.1136/neurintsurg-2020-016427 Ischemic stroke 11 good outcome, reperfusion, or adverse events between patients Departments of Neuroradiology, Department of Clinical Neuroscience, Karolinska with M1 and M2 occlusion, although patients in our cohort with University Hospital, Karolinska Institutet, Stockholm, Sweden 12 Mercy Health St Vincent Medical Center, Toledo, Ohio, USA M2 occlusion did have a lower mean NIHSS score and a trend towards a higher baseline ASPECT score. The primary results Twitter Marc Ribo @marcriboj publication of ARISE II had a table in the online supplemental materials that compared its cohort to that of 11 other studies, Collaborators ARISE II Collaborators: René Chapot, Ashutosh Jadhav, Jonathan and found that the ARISE II cohort had a shorter time from A. Grossberg, Raul G. Nogueira, Tudor G. Jovin, Adnan H. Siddiqui, Mairsil Claffey, stroke onset or last known normal to EVT treatment.8 Time Steven W. Hetts, Werner Hacke, Brijesh P. Mehta, Lofti Hacein-­Bey, Anthony W. Kim, Alex Abou-­Chebl, Peter Shabe, Albert J. Yoo, Guilherme Dabus, Ryan A. Priest, Gary M. from stroke onset to reperfusion is a critical factor in the odds Nesbit, Wayne M. Clark, Masahiro Horikawa, David A. Hoak, Bryan D. Petersen, Noah of achieving good outcome.19 20 The comparatively favorable C. Beadell, Kory S. Herrick, Corey R. White, Michelle T. Stacey, Sierra C. Ford, Jesse J. outcomes for the M1 occlusions in ARISE II may reflect their Liu, Alejandro Tomasello, Carlos A. Molina, David Rodriguez-­Luna, Sandra Boned-­ earlier reperfusion. The EmboTrap also demonstrated higher Riera, Jorge Pagola, Marta Rubiera, Jesus M. Juega, Noelia Rodriguez-­Villatoro, than average rates of successful reperfusion, which may account Hannes Nordmeyer, Michael Stauder, Christian P. Stracke, Markus Heddier, Denis for the better outcomes in this cohort.8 Finally, in a meta-­analysis Herbreteau, Richard Bibi, Oliver Francois, D. Pieters, Tom Dewaele, Paul Bourgeois, of the five randomized controlled trials from 2015 (MR CLEAN, Frederik Vanhee, Patrick Vanderdouckt, Evelien Vancaester, Brian T. Jankowitz, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA), the Andrew F. Ducruet, Amin N. Aghaebrahim, Cynthia L. Kenmuir, Hazem M. Shoirah, median (IQR) ASPECT score of EVT-­treated patients was 97–10 21 Bradley J. Molyneaux, Prasanna K. Tadi, Gena M. Walker, Matthew T. Starr, Diogo C. while in ARISE II it was 10 (9-10). This introduces the possibility Haussen, Michael R. Frankel, Nicolas A. Bianchi, Samir R. Belegaje, Nicole D. Mahdi, Sourabh Lahoti, Anna N. Katema, Melanie J. Winngingham, Aaron M. Anderson, that the better outcomes in ARISE II patients were due to smaller Eugene Lin, Christian H. Riedel, Olav Jansen, Fritz Wodarg, Naomi Larsen, Andreas infarct volumes prior to EVT. Binder, Daniel Wiesen, Kenneth V. Snyder, Elad I. Levy, Jason M. Davies, Ashish Sonig, The present study has several limitations. The most important Leonardo N. Rangel-­Castilla, Ashkan Mowla, Hakeem J. Shakir, Vernard S. Fennel, being that although this was a prespecified analysis, it is a Gursant S. Atwal, Sabareesh K. Natarajan, J. Beecher, John Thornton, Paul Brennan, subgroup of ARISE II with a limited number of M2 occlusions. Alan O’Hare, Hamed Asadi, Ronald F. Budzik, N. Voraco, Peter J. Pema, Thomas M. We also present the results of a study where only one thrombec- David, William J. Hicks, Jennifer D. Mejilla, Mohamed S. Teleb, Peter J. Sunenshine, tomy device was used, which limits the generalizability of our Jacqueline M. Carter, Christian A. Taschner, Stephan Meckel, Samer Elsheik, Horst findings. Another limitation is that four patients were lost to Urbach, Christoph A. Maurer, Karl Egger, Wolf D. Nieson, Blaise W. Baxter, Steven D. follow-­up in the M1 occlusion subgroup compared with none Quarfordt, Justin A. Calvert, Harris E. Hawk, Reza Malek, Arash M. Padidar, Ursula in the M2 occlusion subgroup, which might have introduced Kelly-­Tolley, A. Gutierrez, Pasquale Mordasini, Rupashani Balasubramaniam, Jan Gralla, Urs Fischer, Felix Zibold, Eike I. Piechowiak, Reade A. DeLeacy, Johanna T. Fifi, bias. Furthermore, the lack of a comparator or control group Jay Mocco, Sidney Starkman, Viktor Szeder, Satoshi Tateshima, Gary R. Duckwiler, in ARISE II allows comparison only with published cohorts. A May Nour, Xian N. Tang, Jason D. Hinman, Anita Tipirneni, David S. Liebeskind, Dileep direct comparison would be necessary to draw conclusions about R. Yavagal, S. Suir, Justin M. Caplan, P. Kandewall, Eric C. Peterson, Robert M. Starke, the relative efficacy of the EmboTrap for M2 occlusions. These Ajit S. Puri, David E. Rex, Francesco Massari, Ajay Wakhloo, Juan D. Lozano, Katyucia limitations are offset by several strengths—in particular, the use D. Rodrigues, Laurent Pierot, S. Sebastien, M. G. Emmoinoli of a clinical outcome and central imaging adjudication process Contributors AdH, APN, and OOZ conceived of the study, drafted the manuscript, for reperfusion and intracranial hemorrhage with at least two and edited the manuscript. TA, MR, HPM, HB, JLS, and AA provided critical editing independent raters who were not involved in the trial. In addi- and guidance for the manuscript. tion, the imaging core laboratory adjudicated mTICI score after Funding This study was the academic work of the authors. ARISE II was sponsored the first three and final endovascular thrombectomy passes, by Neuravi, now Cerenovus, part of Johnson & Johnson. AdH is supported by NIH-­ provided data on the full spectrum of mTICI scores (including NINDS K23NS105924. 2c), and was blinded to clinical outcomes. Safety events were Competing interests AdH receives funding from AMAG and Regeneron adjudicated by an independent Clinical Events Committee also pharmaceuticals for investigator initiated research. APN and AA have no personal, financial, or institutional interest to report. JLS is an employee of the University of blinded to clinical data. California, which holds a patent on retriever devices for stroke; the University of California, Regents receives funding for Dr. Saver’s services as a scientific consultant CONCLUSION regarding trial design and conduct to Covidien/Medtronic and Stryker; serves as In ARISE II, the EmboTrap device successfully treated M2 a consultant for Modest, Abbott, Medtronic, Stryker, and Neuravi/Cerenovus; has contracted stock options for Modest and Rapid Medical. HB serves as a modest MCA occlusions in patients with AIS, achieving a 70.2% rate consultant for Neuravi/Cerenovus, and Stryker. HPM reports personal fees from of good outcome at 90 days, which is well above published Covidien/Medtronic, personal fees from Neuravi/Cerenovus, personal fees from rates for untreated M2 occlusions and also superior to prior Servier, and personal fees from Bayer outside the submitted work; served on the reports of EVT-­ treated M2 occlusions. When comparing steering committees of the SWIFT PRIME and ARISE studies. MR is a shareholder in Anaconda Biomed, consultant for Neuravi/Cerenovus, Medtronic, Stryker, Apta the M1 and M2 occlusions in ARISE II, we report similar Targets, and Vesalio. TA is a consultant for Neuravi/Cerenovus, Ablynx, Amnis rates of good outcome, successful reperfusion, death, and Therapeutics, Medtronic, Rapid Medical, and Stryker. OOZ serves as a consultant for other adverse events. The treatment of M2 occlusion in Neuravi/Cerenovus, Stryker, Penumbra, and Medtronic. patients with AIS with the EmboTrap device appears safe and Patient consent for publication Not required. efficacious. Provenance and peer review Not commissioned; externally peer reviewed. Author affiliations Data availability statement All data relevant to the study are included in the 1 Department of Neurology, University of Utah, Salt Lake City, Utah, USA article or uploaded as supplementary information. 2 Service of Radiology and Neuroradiology, University Hospital of Tours, Tours, France Open access This is an open access article distributed in accordance with the 3 Department of Neurosurgery, CHU Tours, Tours, France Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which 4 Hopital Universitaire Pitie Salpetriere, Paris, France permits others to distribute, remix, adapt, build upon this work non-­commercially, 5 Department of Neurology, UCLA, Los Angeles, California, USA and license their derivative works on different terms, provided the original work is 6 Oregon Health and Science University, Portland, Oregon, USA properly cited, appropriate credit is given, any changes made indicated, and the use 7 Department of Neurology, Inselspital, University of Bern, Bern, Switzerland is non-­commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/. 8 Stroke Unit, Neurology, Hospital Vall d’Hebron, Barcelona, Spain 9 Universitat Autònoma de Barcelona, Bellaterra, Spain ORCID iD 10 Departments of Radiology and Neurology, AZ Groeninge, Kortrijk, Belgium Adam de Havenon http://​orcid.​org/​0000-​0001-​8178-​8597 de Havenon A, et al. J NeuroIntervent Surg 2021;13:779–783. doi:10.1136/neurintsurg-2020-016427 5 of 6 Ischemic stroke REFERENCES 10 Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with 1 Hernández-­Pérez M, Pérez de la Ossa N, Aleu A, et al. Natural history of acute stroke selection by perfusion imaging. N Engl J Med 2018;378:708–18. due to occlusion of the middle cerebral artery and intracranial internal carotid artery. J 11 Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom Neuroimaging 2014;24:354–8. onset in ischemic stroke. N Engl J Med 2015;372:2296–306. 2 Chen C-­J, Wang C, Buell TJ, et al. 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