Background and purpose Given the promising performance of the new Embolus Retriever with Interlinked Cages (ERIC) in smaller case series, we sought to assess the efficacy and safety of mechanical thrombectomy (MT) with ERIC compared with other stent retrievers (SRs) in acute ischemic stroke due to large vessel occlusion (LVO).
Methods We reviewed the databases of two comprehensive stroke centers in in Germany and Switzerland for MT due to LVO in the anterior circulation with either ERIC or another SR as a first device. Co-primary outcome was defined as successful recanalization (Thrombolysis in Cerebral Infarction 2b/3) after the first device and favorable outcome (modified Rankin Scale score 0–2) at 90 days' follow-up. Multiple logistic regression analysis was applied to adjust for potential confounders.
Results 183 consecutive patients with stroke were treated with either ERIC (49%) or a SR (51%) as the first device and successful recanalization was seen in 82% and 57%, respectively (P<0.001). Adding SR to futile ERIC recanalization or vice versa increased final recanalization rates (ERIC: 87%, SR: 79%). The use of ERIC as a first device resulted in favorable clinical outcome in 50% compared with 35% when a SR was used (P=0.038), an effect driven by age, stroke severity, presence of carotid-T-occlusion, and general anesthesia and not by the device deployed.
Conclusion The use of ERIC as a first device appeared to be associated with higher rates of successful recanalization and resulted in better functional outcome. However, favorable outcome was not attributable to ERIC. Most importantly, both device types complemented one another and improved final recanalization rates when used successively.
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Early restoration of cerebral blood flow is crucial to prevent persistent brain damage and to promote favorable clinical outcome in acute ischemic stroke.1 Mechanical thrombectomy (MT) in patients with acute ischemic stroke and large vessel occlusion (LVO) using stent retrievers (SRs) is highly effective and safe.2–6 Various SRs, such as the Solitaire or Trevo series among others, are in use.
The Embolus Retriever with Interlinked Cages (ERIC) is an innovative retrieval system and its geometrical design differs substantially from that of other SR systems.7 The special cage design should lead to faster clot integration and should prevent the captured clot from shearing-off during retraction. In addition, the parallel strut design of the individual cages should provide an atraumatic retraction because of a relatively low radial force per strut.
So far, smaller studies have shown the feasibility of ERIC and point towards a reasonable efficacy and safety profile.7–10 The aim of this study was to assess the safety and efficacy of the new ERIC retrieval device compared with other SRs in the largest ERIC cohort to date.
Material and methods
Patients and study design
In this observational retrospective study, the comprehensive stroke centers of the University Hospital Hamburg-Eppendorf, Germany and Cantonal Hospital Aarau, Switzerland systematically searched their stroke database for patients with acute ischemic stroke fulfilling the following inclusion criteria: (a) age ≥18 years, (b) onset-to treatment time of ≤6 hours or wake-up stroke with either relevant CT-perfusion mismatch defined as a time to peak/cerebral blood volume area ratio of ≥2 or Alberta Stroke Program Early CT Score ≥5 in brain CT/MRI; (c) National Institute of health Stroke Scale (NIHSS) score of ≥2; (d) proven LVO in the anterior circulation arteries (internal carotid artery; middle cerebral artery (MCA); anterior cerebral artery) on CT/MRI angiography, and (e) mechanical thrombectomy using ERIC or another SR as a first device. Our standard procedure comprises stent retrieval into an aspiration catheter with proximal balloon occlusion. To rule out comparisons with historical controls, we included patients only during the time when ERIC and SRs were used side by side at the corresponding centers. Approval was obtained from the local ethics committee of the corresponding centers.
Either ERIC or another SR system was used as first device. The choice of the retriever system was at the discretion of the treating neurointerventionalist. Conscious sedation was chosen if possible— that is, absence of agitation, vomitus or respiratory failure. All procedures were performed on biplane angiograph systems according to the departmental protocol with intra-procedural modification if required. After clot retraction, a control angiography was performed to confirm recanalization and grade of reperfusion.
Primary and secondary outcome measures
The co-primary outcomes are successful recanalization (Thrombolysis in Cerebral Infarction (TICI) score 2b/3)11 after the first device and favorable clinical outcome (modified Rankin scale (mRS) score 0–2) at 3 months' follow-up. In addition, we assessed successful recanalization at the end of the whole procedure, procedural time, and the safety parameters symptomatic intracranial hemorrhage (sICH), intraprocedural complications, and in-hospital as well as all-cause mortality at 90 days. One patient in the SR group was lost to 90-day follow-up.
Data were analyzed by STATA/IC 14.1 software package (StataCorp Ltd). Group differences were evaluated using χ2 test for categorical data and Wilcoxon rank-sum test for ordinal or interval data. Univariate and multivariate logistic regression analyses were performed for the co-primary outcome measures. For all results, P≤0.05 was considered to be statistically significant.
We identified 183 consecutive patients with acute ischemic stroke caused by LVO of the anterior circulation, who were treated either with the new ERIC (n=90) or another established SR (n=93) as first device (figure 1).
Patient baseline characteristics
The two groups were well balanced for age, gender, presence of vascular risk factors, stroke severity on admission expressed by the NIHSS score, treatment with intravenous thrombolysis, the distribution of stroke etiology according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification, and the site of intracranial vessel occlusion, except for MCA M2 occlusions, which were predominantly found in ERIC-treated patients (29% vs 11%, P=0.002) (table 1).
Sedation regimen, additional cervical artery stenting, and total number of passes did not differ significantly between the two groups. Time from symptom onset to groin puncture showed a trend for earlier treatment initiation in SR-treated patients (median 267 min IQR (211–405) vs 313 min IQR (219–495), P=0.07). Time from symptom onset to end of procedure and procedural time itself were significantly longer in patients treated with ERIC as a first device. However, the absolute difference in median procedural times was ≤16 min (table 1).
Efficacy and safety
ERIC as the first and only device achieved higher rates of successful recanalization than with SR only (TICI 2b/3 after first device: ERIC 82%, SR 57%, P<0.001), an effect that was robust even after adjusting for potential confounders—in particular, the site of intracranial vessel occlusion (table 1, table 2 and online supplementary table 1).
Supplementary file 1
Of note is the fact that using an additional SR in futile recanalization with ERIC as a first device or using an additional ERIC or another SR in patients initially treated with a SR resulted in similar high final recanalization rates in both groups (TICI 2b/3 final: ERIC as the first retriever 87%, SR as the first device 79%, P=0.06).
The number of sICH and intraprocedural complications was generally low and equally distributed between groups. In-hospital mortality and death at 3 months' follow-up was also comparable in both groups. Favorable outcome (mRS 0–2) at 3 months after the ischemic event was 50% in patients initially treated with ERIC and 35% in SR (P=0.04). After adjusting for baseline and procedural characteristics this effect was driven by age, NIHSS score on admission, the presence of carotid-T occlusion and the need for general anesthesia and not associated with the device used (table 3 and online supplementary table 2).
This study comprises the largest ERIC cohort reported to date and analyzed the use of ERIC or another SR for their efficacy and safety in patients with acute ischemic stroke due to anterior circulation LVO. The use of ERIC as the first and only device was associated with significantly higher rates of successful recanalization compared with a SR only. Successful recanalization with ERIC was achieved in 82% of cases and is in line with previously reported rates with this device ranging from 83% to 87%.7–10 The rate of TICI 2b/3 after the first device using SR was 57% in our study, which was lower than with ERIC but still comparable to the milestone mechanical thrombectomy randomized controlled trial (RCT) MR CLEAN.2 Interestingly, in large recent MT RCTs using a SR, lower rates of successful recanalization were reported when the average time from symptom onset to groin puncture was >4 hours (TICI 2b/3: 59–69%)2 12 13compared with ≤4 hours (73%–88%).6 14 15 This is reflected in the 57% achieving TICI 2b/3 in SR as the first and only device treated group with a median time from symptom onset to groin puncture of 267 min in our study. On the other hand, lacking randomized data for ERIC, recent observational studies point to successful recanalization rates >80% in ERIC-treated patients even if treatment is initiated >4 hours from symptom onset,7–10 including data from the present study (median time from symptom onset to groin puncture: 313 min). Whether successful recanalization is indeed time dependent if SR are used and of less importance if ERIC is applied needs further elucidation. In addition, despite the higher number of MCA M2-segment occlusions in the ERIC group, which might suggest minor strokes with easy to re-open occlusions, only the use of ERIC as the first device and not the site of occlusion or stroke severity remained statistically relevant for achieving successful recanalization after multivariate analysis (table 2).
Moreover, using an additional SR in futile recanalization with ERIC as a first device, or using an additional ERIC or another SR in patients initially treated with SR resulted in similar high final recanalization rates in both groups (87% and 79%).
Favorable functional outcome was significantly higher in patients initially treated with ERIC (50%) and consistent with previous studies using that device (33.3–55.0%). The application of a SR as a first device resulted in favorable clinical outcome 3 months after stroke in 35% of patients, which also matches the result from the large endovascular RCT MR CLEAN.2 However, after statistical adjustment for confounding factors in our non-randomized study, the difference in favorable outcome between the two groups was not related to the type of device used, but was associated with age, NIHSS on admission, the presence of carotid-T-occlusion and the need for general anesthesia.
Although statistically significant, the absolute intergroup difference in median procedural times of ≤16 min does not explain different functional outcomes. In contrast, the statistical trend of later treatment initiation in the ERIC group might account for the missing advantage of ERIC on favorable functional outcome despite higher rates of successful recanalization with ERIC as the first retriever in this study. Furthermore, potential intergroup differences in lesion location, which were not assessed in detail in this study, might contribute to variations in functional outcome16 and should also be examined in future prospective comparative trials.
Of note, ERIC and SR demonstrated similar safety profiles with no significant differences in intraprocedural complications, sICH, in-hospital mortality, and mortality 3 months after stroke. Interestingly, overall mortality 3 months after stroke reaches 30% and was higher than reported in the pivotal MT RCTs17 and comparable to the North American Solitaire Stent Retriever Acute Stroke registry and the TREVO 2 trial.18 19 Advanced age, which was on average 73 years in our study and between 65 and 71 years in the pivotal MT RCTs as well as late onset of vessel reperfusion (313 min vs less than 270 min in the milestone MT RCTs) might account, at least in part, for the current mortality. Still, MT remained beneficial in older patients and patients with delayed reperfusion.20
This study has some major limitations. (1) Owing to the retrospective and non-randomized design of the study, several potential confounders had to be considered. Using multiple logistic regression analysis we tried to adjust the statistics as far as possible. (2) In addition, as this was not a randomized trial, selection of the respective device by the treating interventionalist might bear a relevant bias. However, although we thoroughly searched for potential factors (eg, personal preference, location of occlusion), we were unable to identify a systematic bias towards preference for one device over the other. (3) As distal vessel occlusions were not included, we cannot comment on the efficacy and safety of ERIC or SR in these cases. A recent study applying the pREset lite SR to intracranial occlusions with an average vessel diameter of 1.6 mm showed promising results, with rates of successful recanalization of 70%.21 Future trials comparing devices should also examine recanalization of smaller but relevant vessels. (4) As there are no predefined stringent criteria in our protocols for when to change the device or when to terminate the intervention, procedural times are occasionally extended. (5) Lack of blinding to the type of device used while assessing outcome parameters might have resulted in a bias.
This study showed higher rates of successful recanalization if ERIC was used as the first and only device, an effect, which did not result in better functional outcome. Safety profiles were similar in both groups. Adding a SR to futile recanalizations with ERIC or vice versa increased the rate of final successful recanalization in both groups. Thus, the availability of both, ERIC and established SR, further strengthens the armamentarium of mechanical endovascular thrombectomy devices.
LR and TK contributed equally and share senior authorship. We appreciate the professional cooperation of physicians, nurses, and technical assistants from the Departments of Anesthesiology, Emergency Medicine, Neurology, Neuroradiology, Neurosurgery, and Vascular surgery in the specialized treatment of our patients with acute stroke.
LR and TK contributed equally.
Contributors PG, LR and TK: substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. SZ, CG-E, JB, JA, MD, KN, FF, and JF: the acquisition, analysis or interpretation of data for the work; revising it critically for important intellectual content; final approval of the version to be published and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests JF receives research support from the German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB), Medtronic, Microvention, Philips, Stryker. He is a consultant for Acandis, Cerenovus, Covidien, Medtronic, Microvention, Penumbra, Route92 and Stryker.
Ethics approval Ethikkommission Nordwest- und Zentralschweiz.
Provenance and peer review Not commissioned; externally peer reviewed.
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