Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size.

BACKGROUND: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied. METHODS: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage. RESULTS: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group. CONCLUSIONS: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.).

Intravenous Thrombolysis before Complete Angiographic Reperfusion: Beyond Angiographic Assessment to Target Microvascular Obstruction?

OBJECTIVE: Recent data have suggested that ineffective tissue reperfusion despite successful angiographic reperfusion was partly responsible for unfavorable outcomes after endovascular therapy (EVT) and might be modulated by intravenous thrombolysis (IVT) use before EVT. To specifically decipher the effect played by IVT before EVT, we compared the clinical and safety outcomes of patients who experienced a complete reperfusion at the end of EVT according to IVT use before EVT. METHODS: The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing, prospective, observational study at 21 centers that perform EVT in France. Patients were included if they had an anterior large vessel occlusion of the intracranial internal carotid artery or middle cerebral artery (M1/M2 segments) and complete reperfusion (expanded Thrombolysis in Cerebral Infarction score = 3) with EVT within 6 hours, between January 2015 and December 2021. The cohort was divided into two groups according to IVT use before EVT, and propensity score matching (PSM) was used to balance the two groups. Primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included favorable outcome (mRS 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. Outcomes were estimated with multivariate logistic models adjusted for age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and time from symptom onset to puncture. RESULTS: Among 5,429 patients included in the ETIS registry, 1,093 were included in the study, including 651 patients with complete recanalization treated with IVT before EVT. After PSM, 488 patients treated with IVT before EVT were compared to 337 patients without IVT. In the matched cohort analysis, the IVT+EVT group had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR] = 1.41, 95% confidence interval [CI] = 1.04-1.91, p = 0.023) and higher rates of favorable outcome (61.1% vs 48.7%, aOR = 1.49, 95% CI = 1.02-2.20, p = 0.041) at 90 days compared with the EVT alone group. Rates of symptomatic intracerebral hemorrhage were comparable between both groups (6.0% vs 4.3%, aOR = 1.16, 95% CI = 0.53-2.54, p = 0.709). INTERPRETATION: In clinical practice, even after complete angiographic reperfusion by EVT, prior IVT use improves clinical outcomes of patients without increasing bleeding risk. ANN NEUROL 2024;95:762-773.

The Benefit of a Complete over a Successful Reperfusion Decreases with Time.

OBJECTIVE: Time from stroke onset to reperfusion (TSOR) is strongly associated with outcomes after endovascular treatment. A near-to-complete or complete reperfusion (modified Treatment in Cerebral Ischemia [mTICI] 2c-3) is associated with improved outcomes compared with a successful reperfusion (mTICI 2b). However, it is unknown whether this association remains stable as TSOR increases. Therefore, we sought to investigate the association between TSOR and outcomes according to the reperfusion status. METHODS: We analyzed data from the Endovascular Treatment in Ischemic Stroke registry, a prospective, observational, multicentric study of acute ischemic stroke patients treated with endovascular treatment in 21 centers in France. We included patients with anterior occlusions (M1, internal carotid artery, tandem), with a known time of symptom onset. Outcomes were early neurological improvement at 24 hours and favorable outcome (modified Rankin Scale between 0 and 2) at 90 days. RESULTS: Overall, 4,444 patients were analyzed. Compared with a mTICI 2b, a mTICI 2c-3 at 1 hour was associated with higher mean marginal probabilities of early neurological improvement (25.6%, 95% CI 11.7-39.5, p = 0.0003) and favorable outcome (15.2%, 95% CI 3.0-27.4, p = 0.0143), and progressively declined with TSOR. The benefit of a mTICI 2c-3 over a mTICI 2b was no longer significant regarding the rates of early neurological improvement and favorable outcome after a TSOR of 414 and 344 minutes, respectively. INTERPRETATION: The prognostic value of a complete over a successful reperfusion progressively declined with time, and no difference regarding the rates of favorable outcome was observed between a complete and successful reperfusion beyond 5.7 hours. ANN NEUROL 2023;93:934-941.

Thrombectomy with or without Intravenous Thrombolytics in Basilar Artery Occlusion.

OBJECTIVE: Two randomized trials demonstrated the benefit of endovascular therapy (EVT) in patients suffering from a stroke due to a basilar artery occlusion (BAO). However, intravenous thrombolytic (IVT) use before EVT was low in these trials, questioning the added value of this treatment in this setting. We sought to investigate the efficacy and safety of EVT alone compared to IVT + EVT in stroke patients with a BAO. METHODS: We analyzed data from the Endovascular Treatment in Ischemic Stroke registry, a prospective, observational, multicenter study of acute ischemic stroke patients treated with EVT in 21 centers in France between 1 January 2015 and 31 December 2021. We included patients with BAO and/or intracranial vertebral artery occlusion and compared patients treated with EVT alone versus IVT + EVT after propensity score (PS) matching. Variables selected for the PS were pre-stroke mRS, dyslipidemia, diabetes, anticoagulation, admission mode, baseline NIHSS and ASPECTS, type of anesthesia, and time from symptom onset to puncture. Efficacy outcomes were good functional outcome (modified Rankin Scale [mRS] 0-3) and functional independence (mRS 0-2) at 90 days. Safety outcomes were symptomatic intracranial hemorrhages and all-cause mortality at 90 days. RESULTS: Among 385 patients, 243 (134 EVT alone and 109 IVT + EVT) were included after PS matching. There was no difference between EVT alone and IVT + EVT regarding good functional outcome (adjusted odd ratio [aOR] labeling = 1.27, 95% confidence interval [CI], 0.68-2.37, p = 0.45) and functional independence (aOR = 1.50, 95% CI, 0.79-2.85, p = 0.21). Symptomatic intracranial hemorrhage and all-cause mortality were also similar between the two groups (aOR = 0.42, 95% CI, 0.10-1.79, p = 0.24 and aOR = 0.56, 95% CI, 0.29-1.10, p = 0.09, respectively). INTERPRETATION: In this PS matching analysis, EVT alone seemed to lead to similar neurological recovery than IVT + EVT, with comparable safety profile. However, given our sample size and the observational nature of this study, further studies are needed to confirm these findings. ANN NEUROL 2023;94:596-604.

Tenecteplase versus Alteplase before thrombectomy: A comprehensive evaluation of clinical and angiographic impact: Insights from the ETIS registry.

INTRODUCTION: Data on prior use of Tenecteplase versus Alteplase in acute stroke management by mechanical thrombectomy are controversial. Our primary objective was to make a comprehensive comparative assessment of clinical and angiographic efficacy and safety outcomes in a large prospective observational study. METHODS: We included stroke patients who were eligible for intravenous thrombolysis and endovascular thrombectomy between 2019 and 2021, from an ongoing registry in twenty comprehensive stroke centers in France. We divided patients into two groups based on the thrombolytic agent used (Alteplase vs Tenecteplase). We then compared their treatment times, and their angiographic (TICI scale), clinical (mRS at three months and sICH) and safety outcomes after controlling for potential confounders using propensity score methods. RESULTS: We evaluated 1131 patients having undergone thrombectomy for the final analysis, 250 received Tenecteplase and 881 Alteplase. Both groups were of the same median age (75 vs 74 respectively), and had the same baseline NIHSS score (16) and ASPECTS (8). There was no significant difference for First Pass Effect (OR 0.93, 95 % CI 0.76-1.14, p = 0.75), time required for reperfusion (OR 0.03, 95 % CI 0.09-0.16, p = 0.49), or for final reperfusion status. Clinically, functional independence at 90 days was similar in both groups (OR 0.82, 95 % CI 0.61-1.10, p = 0.18) with the same risk of sICH (OR 1.36, 95 % CI 0.77-2.41, p = 0.28). However, Tenecteplase patients had shorter imaging-to-groin puncture times (99 vs 142 min, p < 0.05). CONCLUSIONS: Tenecteplase showed no better clinical or angiographic impact on thrombectomy compared to Alteplase. Nevertheless, it appeared associated with a shorter thrombolysis-to-groin puncture time.

24-Hour Carotid Stent Patency and Outcomes After Endovascular Therapy: A Multicenter Study.

BACKGROUND: Management of extracranial internal carotid artery steno-occlusive lesion during endovascular therapy remains debated. Stent occlusion within 24 hours of endovascular therapy is a frequent event after acute carotid artery stenting, and we currently lack large population results. We investigated the incidence, predictors, and clinical impact of stent occlusion after acute carotid artery stenting in current clinical practice. METHODS: Patients treated by endovascular therapy with acute carotid artery stenting between 2015 and 2019 in 5 large-volume endovascular-capable centers were retrospectively analyzed. Patients were separated in 2 groups according to the stent patency at 24 hours after carotid artery stenting. We compared baseline characteristics, treatment modalities, and clinical outcome depending on 24-hour stent patency. Primary end point was favorable outcome, defined as a modified Rankin Scale score 0-2 at 3 months. RESULTS: A stent occlusion was observed in 47/225 patients (20.9%). Patients with stent patency had a lower baseline National Institutes of Health Stroke Scale (median [interquartile range]: 13 [7-17] versus 18 [12-21]) and had more often stroke of atherothrombotic origin (77.0% versus 53.2%). A higher stent patency rate was found for patients treated with P2Y12 antagonists at the acute phase (odds ratio [OR]' 2.95 [95% CI' 1.10-7.91]; P=0.026) and treated with angioplasty (OR' 2.42 [95% CI' 1.24-4.67]; P=0.008). A better intracranial angiographic reperfusion was observed in patients with 24-hour stent patency compared with patients without stent patency (OR' 8.38 [95% CI' 3.07-22.78]; P<0.001). Patients with a stent patency at 24 hours had a higher chance of favorable outcome (OR' 3.29 [95% CI, 1.66-6.52]; P<0.001) and a lower risk of death (OR' 0.32 [95% CI, 0.13-0.76]; P=0.009). CONCLUSIONS: One out of 5 patients treated with carotid artery stenting during endovascular therapy presented a stent occlusion within 24 hours. This event was associated with worse functional outcome. Stroke etiology, P2Y12 antagonist administration, quality of intracranial reperfusion, and angioplasty were associated with 24-hour stent patency.

Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial.

BACKGROUND: Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. METHODS: In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0·9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. FINDINGS: Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047). INTERPRETATION: Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. FUNDING: Medtronic and University Hospital Bern.

Parenchymal Hemorrhage Rate Is Associated with Time to Reperfusion and Outcome.

OBJECTIVE: Despite a 90% reperfusion rate, only 50% of patients with anterior circulation large vessel occlusion-related acute ischemic stroke (LVO-AIS) have a functional recovery at 3 months. Parenchymal hematoma (PH) is a predictor of poor outcome after endovascular treatment (EVT). We aim to investigate the relationship between the delay from onset to reperfusion, the occurrence of PH, and functional outcome. METHODS: The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing prospective observational study. Data were analyzed from the subgroup of patients who underwent a successful EVT defined by a modified Thrombolysis in Cerebral Infarction (mTICI) score 2b-3. We assessed the factors associated with PH, (ie, PH1 or PH2 grade according to the European Collaborative Acute Stroke Study 2 (ECASS) classification of hemorrhagic transformation), then evaluated the relationships between PH, delay from onset to reperfusion, and functional recovery defined by a modified Rankin Scale (mRS) of 0-2. RESULTS: We analyzed 2,919 patients with an LVO-related AIS who underwent a successful EVT. Overall, 13.3% of the participant experienced a PH. The rate of PH increased by 2.5% (95% CI 1.5%-3.6%, p < 0.001) for every additional hour of onset to reperfusion delay and was, by comparison with the other study patients, consistently associated with a lower rate of functional recovery 19.7% (95% CI 11.6%-27.7%, p < 0.001) irrespective of time from onset to reperfusion. INTERPRETATION: Our results demonstrate that PH rate is associated with the delay from onset to reperfusion and participates in the relationship between time to reperfusion and outcome. Time is Bleeding. ANN NEUROL 2022;92:882-887.

Effect of small vessel disease severity on blood pressure management after endovascular therapy in the BP TARGET trial.

BACKGROUND AND PURPOSE: Acute ischaemic stroke patients with cerebral small vessel disease (CSVD), including cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs), have worse outcomes. The effect was investigated of two blood pressure strategies (intensive vs. standard) and blood pressure variability (BPV) after reperfusion according to CSVD burden in the BP TARGET trial. METHODS: Patients with available magnetic resonance imaging at baseline were included. CMBs were described as absent or present and WMH severity was described according to the Fazekas classification (0-1, absent-mild; 2-3, moderate to severe). Outcomes consisted of any intracerebral hemorrhage (ICH) at 24 h and favorable outcome at 90 days (modified Rankin Scale score between 0 and 2). RESULTS: In all, 246 patients were included. The intensive systolic blood pressure target was not associated with lower rates of ICH or favorable outcome according to CSVD subgroups (all p values >0.35). Several BPV parameters were associated with increased odds of ICH in patients with CMBs but not in patients without CMBs (diastolic blood pressure coefficient of variation, odds ratio 2.06, 95% confidence interval [CI] 1.13-3.77, in patients with ≥1 CMB vs. 0.94, 95% CI 0.68-1.31, in patients without CMBs, phet  = 0.026). Several diastolic BPV parameters were associated with worse outcomes in patients with severe WMHs but not in patients without WMHs (diastolic blood pressure coefficient of variation, odds ratio 0.32, 95% CI 0.17-0.61, in patients with severe WMHs vs. 1.09, 95% CI 0.67-1.79, in patients without WMHs; phet  = 0.003). CONCLUSION: No effect of the intensive systolic blood pressure management strategy was found on ICH occurrence or functional outcome according to CSVD burden. BPV was associated with higher odds of ICH in patients with CMBs and worse outcome in patients with moderate-to-severe WMHs.

Effects of weather conditions on endovascular treatment case volume for patients with ischemic stroke.

BACKGROUND: Weather conditions have been shown to influence the occurrence of cardiovascular events. We tested the hypothesis that weather parameters may be associated with variations of case volume of endovascular treatment (EVT) for acute ischemic stroke. METHODS: Individual data from the ETIS (Endovascular Treatment in Ischemic Stroke) French national registry were matched to local weather stations. Meteorological parameters (rainfall, humidity, atmospheric pressure, air temperature) were gathered from national online resources. Weather readings and EVT case volumes were annually standardized per weather station and EVT center, and their associations tested with non-parametric univariable and generalized linear statistical models. RESULTS: Between 2015 and 2021, 9913 EVT procedures addressed by 135 primary stroke units were matched to weather conditions. The mean daily case volume per center was 0.41 [StDev 0.33], and there was a median of 0.84 procedures daily linked to a weather station [StDev 0.47]. We found lower atmospheric pressure (ß estimate -0.04; 95%CI[-0.07;-0.03], p<0.001), higher humidity (ß estimate 0.07; 95%CI [0.05;0.09], p<0.001) and lower temperatures (ß estimate -0.08; 95%CI[-0.10;-0.06], p<0.001) to be associated with higher standardized EVT daily case volumes. These associations were stable when testing them across strata of binned EVT standardized case volumes. CONCLUSIONS: Our study suggests that lower ambient temperature, lower atmospheric pressure, and higher air humidity are associated with significantly more daily EVT cases in a European temperate country. These results may provide insight into both system of care optimization at times of climate change and intracranial LVO pathophysiology. REGISTRATION-URL: https://clinicaltrials.gov/ct2/show/NCT03776877.

Dual-layer carotid stenting for symptomatic carotid web: Results from the Caroweb study.

BACKGROUND & PURPOSE: Carotid Web (CaW) is a growingly recognized cause of ischemic stroke, associated with a high recurrence risk. Several therapeutic strategies have been proposed as a tertiary prevention including carotid stenting, endarterectomy and antithrombotic medications. Among these, carotid stenting with dual-layer stent may be promising to adequately cover the focal arterial dysplasia. Our aim was to investigate the safety and efficacy of the Casper stent in the treatment of symptomatic CaW. METHODS: We conducted a retrospective analysis of consecutive patients presenting with a symptomatic CaW and included in the ongoing prospective observational multicenter CAROWEB registry. The study period was January 2015 to December 2021. Inclusion criteria were CaW treated with dual-layer Casper stent. Patients treated with other types of carotid stent, endarterectomy or antithrombotic medication were excluded. Clinical and radiological initial data and outcomes were recorded. RESULTS: twenty-seven patients (with 28 caw) were included. median age was 52 (iqr: 46-68). median delay between index cerebrovascular event and cervical stenting was 9 days (IQR: 6-101). In all cases, the cervical carotid stenting was successfully performed. No major perioperative complication was recorded. No recurrent stroke or transient ischemic attack was observed during a median follow-up time of 272 days (IQR: 114-635). Long-term imaging follow-up was available in 25/28 (89.3%) stented CaW with a median imaging follow-up of 183 days (IQR: 107-676; range: 90-1542). No in-stent occlusion or stenosis was detected. CONCLUSION: In this study, carotid stenting with dual-layer Casper stent in the treatment of symptomatic CaW was effective regarding stroke recurrence prevention and safe, without procedural nor delayed detected adverse event. However, the optimal therapeutic approach of symptomatic CaW still needs to be explored through randomized trials.

Magnitude of Blood Pressure Change After Endovascular Therapy and Outcomes: Insight From the BP-TARGET Trial.

BACKGROUND AND PURPOSE: To assess the association between systolic blood pressure change (ΔSBP) at different time intervals after successful reperfusion with radiographic and clinical outcomes. METHODS: This is a post hoc analysis of the BP-TARGET multicenter trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy). ΔSBP was defined as end of procedure SBP minus mean SBP at different time intervals (15-60 minutes, 1-6 hours, and 6-24 hours postprocedure). The primary outcome was the poor functional outcome (90-day modified Rankin Scale score 3-6). RESULTS: We included a total of 267 patients (130 in the intensive treatment group). Compared with patients with favorable outcome, patients with poor outcome had lower ΔSBP (less SBP reduction) at all times intervals. After adjusting for potential confounders including baseline SBP, both ΔSBP15-60M and ΔSBP6-24H were associated with lower odds of poor outcome (adjusted odds ratio per 5 mm Hg SBP reduction, 0.89 [95% CI, 0.81-0.99], and adjusted odds ratio 0.82 [95% CI, 0.73-0.92], respectively). Concerning safety outcomes, patients with intraparenchymal hemorrhage had lower ΔSBP at all time intervals. ΔSBP15-60M was associated with lower odds of any intraparenchymal hemorrhage (adjusted odds ratio per 5 mm Hg SBP reduction 0.91 [95% CI, 0.83-0.99]). Conversely, ΔSBP was not associated with mortality or neurological deterioration at any time interval. CONCLUSIONS: After successful reperfusion, ΔSBP had a linear relationship with poor outcome and the risk of poor outcome was higher with less reduction from the baseline SBP. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03160677.

Effect of Baseline Antihypertensive Treatments on Stroke Severity and Outcomes in the BP TARGET Trial.

BACKGROUND: Acute ischemic stroke (AIS) patients with a history of hypertension experience worse outcomes, which may be explained by a deleterious impact of the renin-angiotensin system (RAS) overactivation. We sought to investigate whether prestroke antihypertensive treatments (AHT) influenced baseline stroke severity and neurological outcomes, in patients with AIS successfully treated by endovascular therapy. METHODS: We performed a post hoc analysis of the BP TARGET trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy) and included hypertensive patients with available data regarding AHT at admission, categorized as RAS inhibitors (ACE [angiotensin-converting enzyme] inhibitors, ARBs [angiotensin 2 receptor blockers], and ß-blockers) and non-RAS inhibitors (calcium channel blockers and diuretics). Associations of each AHT with National Institutes of Health Stroke Scale (NIHSS) score at baseline were investigated in linear mixed model adjusted for the number of treatments and center. Associations of each AHT with 24-hour NIHSS change, intracranial hemorrhage were performed using linear mixed model adjusted for baseline NIHSS, the number of treatments, center, age, and sex and adjusted for age, sex, diabetes, and current smoking for favorable outcome. All analyses were performed on cases-available data regarding the low number of missing data. RESULTS: Overall, 203 patients with at least one AHT were included. Patients under non-RAS inhibitor treatments had a higher NIHSS score at baseline (adjusted mean difference=3.28 [95% CI, 1.33-5.22]; P=0.001). Conversely, patients under RAS inhibitor treatments had a lower baseline NIHSS score (adjusted mean difference=-2.81 [95% CI, -5.37 to -0.25]; P=0.031). Intracranial hemorrhage occurrence was significantly more frequent in patients under non-RAS inhibitor treatments (adjusted odds ratio of 2.48 [95% CI, 1.12-5.47]; P=0.025). Conversely, the use of RAS inhibitor treatments before AIS was not associated with higher odds of radiographic intracranial hemorrhage. Patients with non-RAS inhibitor treatments had less improvement of NIHSS at 24 hours compared with patients without (adjusted mean difference, 2.83 [95% CI, -0.16 to 5.81]; P=0.063). Baseline RAS inhibitor or noninhibitor treatments were not associated with favorable outcome. CONCLUSIONS: We showed an opposite effect of baseline AHT, based on their effect on the RAS. Patients treated with RAS inhibitor agents before AIS exhibited less severe AIS compared with patients under non-RAS inhibitor treatments, developed less intracranial hemorrhage at 24 hours and had a trend toward better NIHSS score at 24 hours. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03160677.

Impact of Strategy on Clinical Outcome in Large Vessel Occlusion Stroke Successfully Reperfused: ETIS Registry Results.

BACKGROUND AND PURPOSE: Approximately half of the patients with acute ischemic stroke due to anterior circulation large vessel occlusion do not achieve functional independence despite successful reperfusion. We aimed to determine influence of reperfusion strategy (bridging therapy, intravenous thrombolysis alone, or mechanical thrombectomy alone) on clinical outcomes in this population. METHODS: From ongoing, prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke registry in France, all patients with anterior circulation large vessel occlusion who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3) following reperfusion therapy were included. Primary end point was favorable outcome, defined as 90-day modified Rankin Scale score ≤2. Patient groups were compared using those treated with bridging therapy as reference. Differences in baseline characteristics were reduced after propensity score-matching, with a maximum absolute standardized difference of 14% for occlusion site. RESULTS: Among 1872 patients included, 970 (51.8%) received bridging therapy, 128 (6.8%) received intravenous thrombolysis alone, and the remaining 774 (41.4%) received MT alone. The rate of favorable outcome was comparable between groups. Excellent outcome (90-day modified Rankin Scale score 0-1) was achieved more frequently in the bridging therapy group compared with the MT alone (odds ratio after propensity score-matching, 0.70 [95% CI, 0.50-0.96]). Regarding safety outcomes, hemorrhagic complications were similar between the groups, but 90-day mortality was significantly higher in the MT alone group compared with the bridging therapy group (odds ratio, 1.60 [95% CI, 1.09-2.37]). CONCLUSIONS: This real-world observational study of patients with anterior circulation large vessel occlusion demonstrated a similar rate of favorable outcome following successful reperfusion with different therapeutic strategies. However, our results suggest that bridging therapy compared with MT alone is significantly associated with excellent clinical outcome and lower mortality. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03776877.

Blood Pressure Trajectory Groups and Outcome After Endovascular Thrombectomy: A Multicenter Study.

BACKGROUND: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. METHODS: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. RESULTS: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days (P<0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8-6.7], P=0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5-3.2], P<0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1-3.2]; P=0.04). No significant association was found between trajectory group and hemorrhagic transformation. CONCLUSIONS: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

Time from I.V. Thrombolysis to Thrombectomy and Outcome in Acute Ischemic Stroke.

OBJECTIVE: Whether the time from intravenous thrombolysis (IVT) to endovascular treatment (EVT) in patients with acute ischemic stroke has an effect on the functional outcome is unknown. METHODS: The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing, prospective, multicenter, observational study that perform EVT in France. Data were analyzed from patients treated by IVT and EVT between October 2013 and December 2018 in 6 comprehensive stroke centers. In the primary analysis, we assessed the association of time from IVT administration to start of EVT with functional outcome (measured with the modified Rankin Scale [mRS]), by means of ordinal logistic regression. Secondary end points included angiographic and safety outcomes. RESULTS: We analyzed 1,986 patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent IVT and EVT. An increased IVT to start of EVT time was associated with a worse functional outcome at 90 days (mRS = 0-2, adjusted odds ratio [OR] per 30 minutes increase in time = 0.91, 95% confidence interval [CI] = 0.86-0.96; mRS = 0-1, adjusted OR per 30 minutes increase in time = 0.89, 95% CI = 0.84-0.94), a lower chance of modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b to 3 reperfusion (adjusted OR per 30 minutes increase in time = 0.93, 95% CI = 0.87-0.98), and an increased probability of symptomatic intracerebral hemorrhage (adjusted OR per 30 minutes increase in time = 1.09, 95% CI = 0.99-1.18). INTERPRETATION: These findings provide a basis for further studies to determine if the functional outcome of patients with stroke can be greatly improved by optimizing IVT to EVT times. ANN NEUROL 2021;89:511-519.

Mechanical thrombectomy failure in anterior circulation strokes: Outcomes and predictors of favorable outcome.

BACKGROUND AND PURPOSE: Despite continuous improvement and growing knowledge in the endovascular therapy of large vessel occlusion stroke (LVOS), mechanical thrombectomy (MT) still fails to obtain satisfying intracranial recanalization in 10% to 15% of cases. However, little is known regarding clinical and radiological outcomes among this singularly underexplored subpopulation undergoing failed MT. We aimed to investigate the outcome after failed MT and identify predictive factors of favorable outcome despite recanalization failure. METHODS: We conducted a retrospective analysis of consecutive patients prospectively included in the ongoing observational multicenter Endovascular Treatment in Ischemic Stroke registry from January 2015 to September 2020. Patients presenting with anterior circulation LVOS treated with MT but experiencing failed intracranial recanalization defined as final modified Thrombolysis In Cerebral Infarction (mTICI) score of 0, 1 and 2a were included. Clinical and radiological outcomes were assessed along with the exploration of predictive factors of Day-90 favorable outcome. RESULTS: The study population comprised 533 patients. Mean age was 68.8 ± 16 years, and median admission National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) were 17 (IQR 12-21) and 7 (IQR 5-8), respectively. Favorable outcomes were observed in 85 patients (18.2%) and 186 died (39.0%). The rate of symptomatic intracranial hemorrhage was 14.1%. In multivariable analysis, younger age (odds ratio [OR] 0.96, 95% CI 0.94-0.98, p < 0.001), a lower admission NIHSS (OR 0.87, 95% CI 0.83-0.91, p < 0.001), a lower number of MT passes (OR 0.77, 95% CI 0.77-0.87, p < 0.001), a lower delta ASPECTS between initial and Day-1 imaging (OR 0.83, 95% CI 0.71-0.98, p = 0.026) and stroke etiology [significant difference among etiological subtypes (p = 0.024) with a tendency toward more favorable outcomes for dissection (OR 2.01, 95% CI 0.71-5.67)] were significantly associated with a 90-day favorable outcome. CONCLUSIONS: In this large retrospective analysis of a multicenter registry, we quantified the poor outcome after MT failure. We also identified factors associated with favorable outcome despite recanalization failure that might influence therapeutic management.

Endovascular Therapy of Anterior Circulation Tandem Occlusions: Pooled Analysis From the TITAN and ETIS Registries.

Background and Purpose: Endovascular therapy for tandem occlusion strokes of the anterior circulation is an effective and safe treatment. The best treatment approach for the cervical internal carotid artery (ICA) lesion is still unknown. In this study, we aimed to compare the functional and safety outcomes between different treatment approaches for the cervical ICA lesion during endovascular therapy for acute ischemic strokes due to tandem occlusion in current clinical practice. Methods: Individual patients' data were pooled from the French prospective multicenter observational ETIS (Endovascular Treatment in Ischemic Stroke) and the international TITAN (Thrombectomy in Tandem Lesions) registries. TITAN enrolled patients from January 2012 to September 2016, and ETIS from January 2013 to July 2019. Patients with acute ischemic stroke due to anterior circulation tandem occlusion who were treated with endovascular therapy were included. Patients were divided based on the cervical ICA lesion treatment into stent and no-stent groups. Outcomes were compared between the two treatment groups using propensity score methods. Results: A total of 603 patients were included, of whom 341 were treated with acute cervical ICA stenting. In unadjusted analysis, the stent group had higher rate of favorable outcome (90-day modified Rankin Scale score, 0­2; 57% versus 45%) and excellent outcome (90-day modified Rankin Scale score, 0­1; 40% versus 27%) compared with the no-stent group. In inverse probability of treatment weighting propensity score­adjusted analyses, stent group had higher odds of favorable outcome (adjusted odds ratio, 1.09 [95% CI, 1.01­1.19]; P=0.036) and successful reperfusion (modified Thrombolysis in Cerebral Ischemia score, 2b-3; adjusted odds ratio, 1.19 [95% CI, 1.11­1.27]; P<0.001). However, stent group had higher odds of any intracerebral hemorrhage (adjusted odds ratio, 1.10 [95%, 1.02­1.19]; P=0.017) but not higher rate of symptomatic intracerebral hemorrhage or parenchymal hemorrhage type 2. Subgroup analysis demonstrated heterogeneity according to the lesion type (atherosclerosis versus dissection; P for heterogeneity, 0.01), and the benefit from acute carotid stenting was only observed for patients with atherosclerosis. Conclusions: Patients treated with acute cervical ICA stenting for tandem occlusion strokes had higher odds of 90-day favorable outcome, despite higher odds of intracerebral hemorrhage; however, most of the intracerebral hemorrhages were asymptomatic.

First-Pass Effect in Basilar Artery Occlusions: Insights From the Endovascular Treatment of Ischemic Stroke Registry.

BACKGROUND AND PURPOSE: In the settings of thrombectomy, the first-pass effect (FPE), defined by a complete recanalization after one pass with no rescue therapy, has been shown to be associated with an improved outcome. As this phenomenon has been predominantly described in anterior circulation strokes, we aimed to study the prevalence, outcomes, and predictors of FPE in patients with a basilar artery occlusion. METHODS: From a prospective multicentric registry, we collected the data of all consecutive basilar artery occlusion patients who underwent thrombectomy and compared the outcomes of patients who achieved FPE and those who did not. We also compared FPE patients with those who achieved a complete recanalization with >1 pass. Finally, a multivariate analysis was performed to determine the predictors of FPE. RESULTS: Data from 280 patients were analyzed in our study, including 84 of 280 patients (30%) with an atheromatous etiology. An FPE was achieved in 93 patients (33.2%), with a significantly higher proportion of good outcomes (modified Rankin Scale score 0-2 at 3 months) and lower mortality than non-FPE patients. An FPE was also associated with improved outcomes compared with patients who went on to have full recanalization with >1 pass. Contact aspiration as first-line strategy was a strong predictor of FPE, whereas baseline antiplatelets and atheromatous etiology were negative predictors. CONCLUSIONS: In our study, an FPE was achieved in approximately one-third of patients with a basilar artery occlusion and was associated with improved outcomes. More research is needed to improve devices and techniques to increase the incidence of FPE. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03776877.

Effect of Operator's Experience on Proficiency in Mechanical Thrombectomy: A Multicenter Study.

BACKGROUND AND PURPOSE: We aimed to evaluate among trained interventional neuroradiologist, whether increasing individual experience was associated with an improvement in mechanical thrombectomy (MT) procedural performance metrics. METHODS: Individual MT procedural data from 5 centers of the Endovascular Treatment in Ischemic Stroke registry and 2 additional high-volume stroke centers were pooled. Operator experience was defined for each operator as a continuous variable, cumulating the number of MT procedures performed since January 2015, as MT became standard of care or, if later than this date, since the operator started performing mechanical thrombectomies in autonomy. We tested the associations between operator's experience and procedural metrics. RESULTS: A total of 4516 procedures were included, performed by 36 operators at 7 distinct centers, with a median of 97.5 endovascular treatment procedures per operator (interquartile range, 57-170.2) over the study period. Higher operator's experience, analyzed as a continuous variable, was associated with a significantly shorter procedural duration (ß estimate, -3.98 [95% CI, -5.1 to -2.8]; P<0.001), along with local anesthesia and M1 occlusion location in multivariable models. Increasing experience was associated with better Thrombolysis in Cerebral Infarction scores (estimate, 1.02 [1-1.04]; P=0.013). CONCLUSIONS: In trained interventional neuroradiologists, increasing experience in MT is associated with significantly shorter procedural duration and better reperfusion rates, with a theoretical ceiling effect observed after around 100 procedures. These results may inform future training and practice guidelines to set minimal experience standards before autonomization, and to set-up operators' recertification processes tailored to individual case volume and prior experience.