Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion.

BACKGROUND: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited. METHODS: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control). The primary outcome was good functional status, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]), at 90 days. Secondary outcomes included a modified Rankin scale score of 0 to 2, distribution across the modified Rankin scale score categories, and quality of life. Safety outcomes included symptomatic intracranial hemorrhage at 24 to 72 hours, 90-day mortality, and procedural complications. RESULTS: Of the 507 patients who underwent screening, 340 were in the intention-to-treat population, with 226 assigned to the thrombectomy group and 114 to the control group. Intravenous thrombolysis was used in 31% of the patients in the thrombectomy group and in 34% of those in the control group. Good functional status at 90 days occurred in 104 patients (46%) in the thrombectomy group and in 26 (23%) in the control group (adjusted rate ratio, 2.06; 95% confidence interval [CI], 1.46 to 2.91, P<0.001). Symptomatic intracranial hemorrhage occurred in 12 patients (5%) in the thrombectomy group and in none in the control group. Results for the secondary clinical and imaging outcomes were generally in the same direction as those for the primary outcome. Mortality at 90 days was 37% in the thrombectomy group and 55% in the control group (adjusted risk ratio, 0.66; 95% CI, 0.52 to 0.82). Procedural complications occurred in 14% of the patients in the thrombectomy group, including one death due to arterial perforation. CONCLUSIONS: In a trial involving Chinese patients with basilar-artery occlusion, approximately one third of whom received intravenous thrombolysis, endovascular thrombectomy within 12 hours after stroke onset led to better functional outcomes at 90 days than best medical care but was associated with procedural complications and intracerebral hemorrhage. (Funded by the Program for Innovative Research Team of the First Affiliated Hospital of USTC and others; ATTENTION ClinicalTrials.gov number, NCT04751708.).

Which Acute Ischemic Stroke Patients Are Fast Progressors?: Results From the ESCAPE Trial Control Arm.

BACKGROUND AND PURPOSE: Fast infarct progression in acute ischemic stroke has a severe impact on patient prognosis and benefit of endovascular thrombectomy. In this post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), we identified acute ischemic stroke patients with rapid infarct growth and investigated their baseline clinical and imaging characteristics. METHODS: Control arm patients were included if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging. Clinical and imaging baseline characteristics were compared between fast progressors and other patients, and occlusion site and collateral flow patterns were assessed in detail. RESULTS: Fast infarct progression occurred in 15 of 43 included patients (34.9%). Fast progressors had worse collaterals (poor in 3/15 [20%] versus 0/28 patients, P=0.021) and more carotid-T or -L occlusions (8/15 [53.4%] versus 3/28[10.7%], P=0.021). In 8 out of 15 (53.3%), occlusion site and circle of Willis configuration prevented collateral flow via the anterior or posterior cerebral artery. CONCLUSIONS: Most patients with fast infarct progression had terminal carotid occlusions and impaired collateral flow via the anterior or posterior cerebral artery, indicating that occlusion location and intracranial vascular anatomy are relevant for infarct progression.

Stroke Imaging Selection Modality and Endovascular Therapy Outcomes in the Early and Extended Time Windows.

BACKGROUND AND PURPOSE: Advanced imaging has been increasingly used for patient selection in endovascular stroke therapy. The impact of imaging selection modality on endovascular stroke therapy clinical outcomes in extended time window remains to be defined. We aimed to study this relationship and compare it to that noted in early-treated patients. METHODS: Patients from a prospective multicentric registry (n=2008) with occlusions involving the intracranial internal carotid or the M1- or M2-segments of the middle cerebral arteries, premorbid modified Rankin Scale score 0 to 2 and time to treatment 0 to 24 hours were categorized according to treatment times within the early (0-6 hour) or extended (6-24 hour) window as well as imaging modality with noncontrast computed tomography (NCCT)±CT angiography (CTA) or NCCT±CTA and CT perfusion (CTP). The association between imaging modality and 90-day modified Rankin Scale, analyzed in ordinal (modified Rankin Scale shift) and dichotomized (functional independence, modified Rankin Scale score 0-2) manner, was evaluated and compared within and across the extended and early windows. RESULTS: In the early window, 332 patients were selected with NCCT±CTA alone while 373 also underwent CTP. After adjusting for identifiable confounders, there were no significant differences in terms of 90-day functional disability (ordinal shift: adjusted odd ratio [aOR], 0.936 [95% CI, 0.709-1.238], P=0.644) or independence (aOR, 1.178 [95% CI, 0.833-1.666], P=0.355) across the CTP and NCCT±CTA groups. In the extended window, 67 patients were selected with NCCT±CTA alone while 180 also underwent CTP. No significant differences in 90-day functional disability (aOR, 0.983 [95% CI, 0.81-1.662], P=0.949) or independence (aOR, 0.640 [95% CI, 0.318-1.289], P=0.212) were seen across the CTP and NCCT±CTA groups. There was no interaction between the treatment time window (0-6 versus 6-24 hours) and CT selection modality (CTP versus NCCT±CTA) in terms of functional disability at 90 days (P=0.45). CONCLUSIONS: CTP acquisition was not associated with better outcomes in patients treated in the early or extended time windows. While confirmatory data is needed, our data suggests that extended window endovascular stroke therapy may remain beneficial even in the absence of advanced imaging.

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct.

BACKGROUND: The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. METHODS: We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days. RESULTS: A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00). CONCLUSIONS: Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .).

Aspiration thrombectomy versus stent retriever thrombectomy as first-line approach for large vessel occlusion (COMPASS): a multicentre, randomised, open label, blinded outcome, non-inferiority trial.

BACKGROUND: Stent retriever thrombectomy of large-vessel occlusion results in better outcomes than medical therapy alone. Alternative thrombectomy strategies, particularly a direct aspiration as first pass technique, while promising, have not been rigorously assessed for clinical efficacy in randomised trials. We designed COMPASS to assess whether patients treated with aspiration as first pass have non-inferior functional outcomes to those treated with a stent retriever as first line. METHODS: We did a multicentre, randomised, open label, blinded outcome, core lab adjudicated non-inferiority trial at 15 sites (ten hospitals and four specialty clinics in the USA and one hospital in Canada). Eligible participants were patients presenting with acute ischaemic stroke from anterior circulation large-vessel occlusion within 6 h of onset and an Alberta Stroke Program Early CT Score of greater than 6. We randomly assigned participants (1:1) via a central web-based system without stratification to either direct aspiration first pass or stent retriever first line thrombectomy. Those assessing primary outcomes via clinical examinations were masked to group assignment as they were not involved in the procedures. Physicians were allowed to use adjunctive technology as was consistent with their standard of care. The null hypothesis for this study was that patients treated with aspiration as first pass achieve inferior outcomes compared with those treated with a stent retriever first line approach. The primary outcome was non-inferiority of clinical functional outcome at 90 days as measured by the percentage of patients achieving a modified Rankin Scale score of 0-2, analysed by intent to treat; non-inferiority was established with a margin of 0·15. All randomly assigned patients were included in the safety analyses. This trial is registered at ClinicalTrials.gov, number: NCT02466893. FINDINGS: Between June 1, 2015, and July 5, 2017, we assigned 270 patients to treatment: 134 to aspiration first pass and 136 to stent retriever first line. A modified Rankin score of 0-2 at 90 days was achieved by 69 patients (52%; 95% CI 43·8-60·3) in the aspiration group and 67 patients (50%; 41·6-57·4) in the stent retriever group, showing that aspiration as first pass was non-inferior to stent retriever first line (pnon-inferiority=0·0014). Intracranial haemorrhage occurred in 48 (36%) of 134 in the aspiration first pass group, and 46 (34%) of 135 in the stent retriever first line group. All-cause mortality at 3 months occurred in 30 patients (22%) in both groups. INTERPRETATION: A direct aspiration as first pass thrombectomy conferred non-inferior functional outcome at 90 days compared with stent retriever first line thrombectomy. This study supports the use of direct aspiration as an alternative to stent retriever as first-line therapy for stroke thrombectomy. FUNDING: Penumbra.

WEAVE Trial: Final Results in 152 On-Label Patients.

Background and Purpose- The WEAVE trial (Wingspan Stent System Post Market Surveillance) is a postmarket surveillance trial mandated by the Food and Drug Administration to assess the periprocedural safety of the Wingspan Stent system in the treatment of symptomatic intracranial atherosclerotic disease. Methods- A total of 152 consecutive patients who met the Food and Drug Administration on-label usage criteria were enrolled at 24 hospitals and underwent angioplasty and stenting with the Wingspan stent. On-label criteria included age 22 to 80 years, symptomatic intracranial atherosclerotic stenosis of 70% to 99%, baseline modified Rankin Scale score ≤3, ≥2 strokes in the vascular territory of the stenotic lesion with at least 1 stroke while on medical therapy, and stenting of the lesion ≥8 days after the last stroke. The primary analysis assessed the periprocedural stroke, bleed, and death rate within 72 hours of the procedure with adjudication by a core study Stroke Neurologist. Results- The trial was stopped early after interim analysis of 152 consecutive patients demonstrated a lower than expected 2.6% (4/152 patients) periprocedural stroke, bleed, and death rate. This was lower than the 4% periprocedural primary event safety benchmark set for the interim analysis in the study. A total of 97.4% (148/152) patients were event-free at 72 hours, 1.3% (2/152) had nonfatal strokes, and 1.3% (2/152) of patients died. Conclusions- With experienced interventionalists, and proper patient selection following the on-label usage guidelines, the use of the Wingspan stent for intracranial atherosclerotic disease demonstrated a low periprocedural complication rate and excellent safety profile. This is the largest on-label, multicenter, prospective trial of the Wingspan stent system to date with the lowest reported complication rate. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02034058.

Influence of Guidelines in Endovascular Therapy Decision Making in Acute Ischemic Stroke: Insights From UNMASK EVT.

Background and Purpose- The American Heart Association and the American Stroke Association guidelines for early management of patients with ischemic stroke offer guidance to physicians involved in acute stroke care and clarify endovascular treatment indications. The purpose of this study was to assess concordance of physicians' endovascular treatment decision-making with current American Heart Association and the American Stroke Association stroke treatment guidelines using a survey-approach and to explore how decision-making in the absence of guideline recommendations is approached. Methods- In an international cross-sectional survey (UNMASK-EVT), physicians were randomly assigned 10 of 22 case scenarios (8 constructed with level 1A and 11 with level 2B evidence for endovascular treatment and 3 scenarios without guideline coverage) and asked to declare their treatment approach (1) under their current local resources and (2) assuming there were no external constraints. The proportion of physicians offering endovascular therapy (EVT) was calculated. Subgroup analysis was performed for different specialties, geographic regions, with regard to physicians' age, endovascular, and general stroke treatment experience. Results- When facing level 1A evidence, participants decided in favor of EVT in 86.8% under current local resources and in 90.6% under assumed ideal conditions, that is, 9.4% decided against EVT even under assumed ideal conditions. In case scenarios with level 2B evidence, 66.3% decided to proceed with EVT under current local resources and 69.7% under assumed ideal conditions. Conclusions- There is potential for improving thinking around the decision to offer endovascular treatment, since physicians did not offer EVT even under assumed ideal conditions in 9.4% despite facing level 1A evidence. A majority of physicians would offer EVT even for level 2B evidence cases.

Factors Associated With the Decision-Making on Endovascular Thrombectomy for the Management of Acute Ischemic Stroke.

Background and Purpose- Little is known about the real-life factors that clinicians use in selection of patients that would receive endovascular treatment (EVT) in the real world. We sought to determine patient, practitioner, and health system factors associated with therapeutic decisions around endovascular treatment. Methods- We conducted a multinational cross-sectional web-based study comprising of 607 clinicians and interventionalists from 38 countries who are directly involved in acute stroke care. Participants were randomly allocated to 10 from a pool of 22 acute stroke case scenarios. Each case was classified as either Class I, Class II, or unknown evidence according to the current guidelines. We used logistic regression analysis applying weight of evidence approach. Main outcome measures were multilevel factors associated with EVT, adherence to current EVT guidelines, and practice gaps between current and ideal practice settings. Results- Of the 1330 invited participants, 607 (45.6%) participants completed the study (53.7% neurologists, 28.5% neurointerventional radiologists, 17.8% other clinicians). The weighed evidence approach revealed that National Institutes of Health Stroke Scale (34.9%), level of evidence (30.2%), ASPECTS (Alberta Stroke Program Early CT Score) or ischemic core volume (22.4%), patient's age (21.6%), and clinicians' experience in EVT use (19.3%) are the most important factors for EVT decision. Of 2208 responses that met Class I evidence for EVT, 1917 (86.8%) were in favor of EVT. In case scenarios with no available guidelines, 1070 of 1380 (77.5%) responses favored EVT. Comparison between current and ideal practice settings revealed a small practice gap (941 of 6070 responses, 15.5%). Conclusions- In this large multinational survey, stroke severity, guideline-based level of evidence, baseline brain imaging, patients' age and physicians' experience were the most relevant factors for EVT decision-making. The high agreement between responses and Class I guideline recommendations and high EVT use even when guidelines were not available reflect the real-world acceptance of EVT as standard of care in patients with disabling acute ischemic stroke.

Standards of Practice in Acute Ischemic Stroke Intervention International Recommendations.

After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.

Computed Tomographic Perfusion Predicts Poor Outcomes in a Randomized Trial of Endovascular Therapy.

BACKGROUND AND PURPOSE: In the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), patients with large vessel occlusions and small infarct cores identified with computed tomography (CT)/CT angiography were randomized to endovascular therapy or standard of care. CT perfusion (CTP) was obtained in some cases but was not used to select patients. We tested the hypothesis that patients with penumbral CTP patterns have higher rates of good clinical outcome. METHODS: All CTP data acquired in ESCAPE patients were analyzed centrally using a semiautomated perfusion threshold-based approach. A penumbral pattern was defined as an infarct core <70 mL, penumbral volume >15 mL, and a total hypoperfused volume:core volume ratio of >1.8. The primary outcome was good functional outcome at 90 days (modified Rankin Scale score, 0-2). RESULTS: CTP was acquired in 138 of 316 ESCAPE patients. Penumbral patterns were present in 116 of 128 (90.6%) of patients with interpretable CTP data. The rate of good functional outcome in penumbral pattern patients (53 of 114; 46%) was higher than that in nonpenumbral patients (2 of 12; 17%; P=0.041). In penumbral patients, endovascular therapy increased the likelihood of a good clinical outcome (34 of 58; 57%) compared with those in the control group (19 of 58; 33%; odds ratio, 2.68; 95% confidence interval, 1.25-5.76; P=0.011). Only 3 of 12 nonpenumbral patients were randomized to the endovascular group, preventing an analysis of treatment effect. CONCLUSIONS: The majority of patients with CTP imaging in the ESCAPE trial had penumbral patterns, which were associated with better outcomes overall. Patients with penumbra treated with endovascular therapy had the greatest odds of good functional outcome. Nonpenumbral patients were much less likely to achieve good outcomes.

Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.

BACKGROUND: Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome. METHODS: We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death]). RESULTS: The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12). CONCLUSIONS: In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.).

Randomized assessment of rapid endovascular treatment of ischemic stroke.

BACKGROUND: Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. METHODS: We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). RESULTS: The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P<0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P<0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P=0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P=0.75). CONCLUSIONS: Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality. (Funded by Covidien and others; ESCAPE ClinicalTrials.gov number, NCT01778335.).

Analysis of Workflow and Time to Treatment on Thrombectomy Outcome in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) Randomized, Controlled Trial.

BACKGROUND: The Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial used innovative imaging and aggressive target time metrics to demonstrate the benefit of endovascular treatment in patients with acute ischemic stroke. We analyze the impact of time on clinical outcome and the effect of patient, hospital, and health system characteristics on workflow within the trial. METHODS AND RESULTS: Relationship between outcome (modified Rankin Scale) and interval times was modeled by using logistic regression. Association between time intervals (stroke onset to arrival in endovascular-capable hospital, to qualifying computed tomography, to groin puncture, and to reperfusion) and patient, hospital, and health system characteristics were modeled by using negative binomial regression. Every 30-minute increase in computed tomography-to-reperfusion time reduced the probability of achieving a functionally independent outcome (90-day modified Rankin Scale 0-2) by 8.3% (P=0.006). Symptom onset-to-imaging time was not associated with outcome (P>0.05). Onset-to-endovascular hospital arrival time was 42% (34 minutes) longer among patients receiving intravenous alteplase at the referring hospital (drip and ship) versus direct transfer (mothership). Computed tomography-to-groin puncture time was 15% (8 minutes) shorter among patients presenting during work hours versus off hours, 41% (24 minutes) shorter in drip-ship patients versus mothership, and 43% (22 minutes) longer when general anesthesia was administered. The use of a balloon guide catheter during endovascular procedures shortened puncture-to-reperfusion time by 21% (8 minutes). CONCLUSIONS: Imaging-to-reperfusion time is a significant predictor of outcome in the ESCAPE trial. Inefficiencies in triaging, off-hour presentation, intravenous alteplase administration, use of general anesthesia, and endovascular techniques offer major opportunities for improvement in workflow. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Ischemic core and hypoperfusion volumes predict infarct size in SWIFT PRIME.

OBJECTIVE: Within the context of a prospective randomized trial (SWIFT PRIME), we assessed whether early imaging of stroke patients, primarily with computed tomography (CT) perfusion, can estimate the size of the irreversibly injured ischemic core and the volume of critically hypoperfused tissue. We also evaluated the accuracy of ischemic core and hypoperfusion volumes for predicting infarct volume in patients with the target mismatch profile. METHODS: Baseline ischemic core and hypoperfusion volumes were assessed prior to randomized treatment with intravenous (IV) tissue plasminogen activator (tPA) alone versus IV tPA + endovascular therapy (Solitaire stent-retriever) using RAPID automated postprocessing software. Reperfusion was assessed with angiographic Thrombolysis in Cerebral Infarction scores at the end of the procedure (endovascular group) and Tmax > 6-second volumes at 27 hours (both groups). Infarct volume was assessed at 27 hours on noncontrast CT or magnetic resonance imaging (MRI). RESULTS: A total of 151 patients with baseline imaging with CT perfusion (79%) or multimodal MRI (21%) were included. The median baseline ischemic core volume was 6 ml (interquartile range= 0-16). Ischemic core volumes correlated with 27-hour infarct volumes in patients who achieved reperfusion (r = 0.58, p < 0.0001). In patients who did not reperfuse (<10% reperfusion), baseline Tmax > 6-second lesion volumes correlated with 27-hour infarct volume (r = 0.78, p = 0.005). In target mismatch patients, the union of baseline core and early follow-up Tmax > 6-second volume (ie, predicted infarct volume) correlated with the 27-hour infarct volume (r = 0.73, p < 0.0001); the median absolute difference between the observed and predicted volume was 13 ml. INTERPRETATION: Ischemic core and hypoperfusion volumes, obtained primarily from CT perfusion scans, predict 27-hour infarct volume in acute stroke patients who were treated with reperfusion therapies.

Clinical and Procedural Predictors of Outcomes From the Endovascular Treatment of Posterior Circulation Strokes.

BACKGROUND AND PURPOSE: Patients with posterior circulation strokes have been excluded from recent randomized endovascular stroke trials. We reviewed the recent multicenter experience with endovascular treatment of posterior circulation strokes to identify the clinical, radiographic, and procedural predictors of successful recanalization and good neurological outcomes. METHODS: We performed a multicenter retrospective analysis of consecutive patients with posterior circulation strokes, who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including A Direct Aspiration First Pass Technique [ADAPT] approach). We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. RESULTS: A total of 100 patients were included in the final analysis (mean age, 63.5±14.2 years; mean admission National Institutes of Health Stroke Scale score, 19.2±8.2). Favorable clinical outcome at 3 months (modified Rankin Scale score ≤2) was achieved in 35% of patients. Successful recanalization and shorter time from stroke onset to the start of the procedure were significant predictors of favorable clinical outcome at 90 days. Stent retriever and aspiration thrombectomy as primary treatment approaches showed comparable procedural and clinical outcomes. None of the baseline advanced imaging modalities (magnetic resonance imaging, computed tomographic perfusion, or computed tomography angiography assessment of collaterals) showed superiority in selecting patients for thrombectomy. CONCLUSIONS: Time to the start of the procedure is an important predictor of clinical success after thrombectomy in patients with posterior circulation strokes. Both stent retriever and aspiration thrombectomy as primary treatment approaches are effective in achieving successful recanalization.

Intra-Arterial Therapy and Post-Treatment Infarct Volumes: Insights From the ESCAPE Randomized Controlled Trial.

BACKGROUND AND PURPOSE: The goal of reperfusion therapy in acute ischemic stroke is to limit brain infarction. The objective of this study was to investigate whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in post-treatment infarct volume. METHODS: The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 315 enrolled subjects (endovascular treatment n=165; control n=150), 314 subject's infarct volumes at 24 to 48 hours on magnetic resonance imaging (n=254) or computed tomography (n=60) were measured. Post-treatment infarct volumes were compared by treatment assignment and recanalization/reperfusion status. Appropriate statistical models were used to assess relationship between baseline clinical and imaging variables, post-treatment infarct volume, and functional status at 90 days (modified Rankin Scale). RESULTS: Median post-treatment infarct volume in all subjects was 21 mL (interquartile range =65 mL), in the intervention arm, 15.5 mL (interquartile range =41.5 mL), and in the control arm, 33.5 mL (interquartile range =84 mL; P<0.01). Baseline National Institute of Health Stroke Scale (P<0.01), site of occlusion (P<0.01), baseline noncontrast computed tomographic scan Alberta Stroke Program Early CT score (ASPECTS) (P<0.01), and recanalization (P<0.01) were independently associated with post-treatment infarct volume, whereas age, sex, treatment type, intravenous alteplase, and time from onset to randomization were not (P>0.05). Post-treatment infarct volume (P<0.01) and delta National Institute of Health Stroke Scale (P<0.01) were independently associated with 90-day modified Rankin Scale, whereas laterality (left versus right) was not. CONCLUSIONS: These results support the primary results of the ESCAPE trial and show that the biological underpinning of the success of endovascular therapy is a reduction in infarct volume. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Aspiration Thrombectomy After Intravenous Alteplase Versus Intravenous Alteplase Alone.

BACKGROUND AND PURPOSE: Thrombectomy, primarily with stent retrievers with or without adjunctive aspiration, provided clinical benefit across multiple prospective randomized trials. Whether this benefit is exclusive to stent retrievers is unclear. METHODS: THERAPY (The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke; NCT01429350) was an international, multicenter, prospective, randomized (1:1), open label, blinded end point evaluation, concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase (IAT) administration compared with intravenous-alteplase alone in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm. The primary efficacy end point was the percent of patients achieving independence at 90 days (modified Rankin Scale score, 0-2; intention-to-treat analysis). The primary safety end point was the rate of severe adverse events (SAEs) by 90 days (as treated analysis). Patients were randomized 1:1 across 36 centers in 2 countries (United States and Germany). RESULTS: Enrollment was halted after 108 (55 IAT and 53 intravenous) patients (of 692 planned) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone. Functional independence was achieved in 38% IAT and 30% intravenous intention-to-treat groups (P=0.52). Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 (95% confidence interval, 0.86-3.59; P=0.12) in favor of IAT. Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT. No differences in symptomatic intracranial hemorrhage rates (9.3% IAT versus 9.7% intravenous, P=1.0) or 90-day mortality (IAT: 12% versus intravenous: 23.9%, P=0.18) were observed. CONCLUSIONS: THERAPY did not achieve its primary end point in this underpowered sample. Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit. It is possible that an alternate method of thrombectomy, primary aspiration, will benefit selected patients harboring large vessel occlusions. Further study on this topic is indicated. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350.

Infarct in a New Territory After Treatment Administration in the ESCAPE Randomized Controlled Trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times).

BACKGROUND AND PURPOSE: Infarct in a new previously unaffected territory (INT) is a potential complication of endovascular treatment. We applied a recently proposed methodology to identify and classify INTs in the ESCAPE randomized controlled trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). METHODS: The core laboratory identified INTs on 24-hour follow-up imaging, blinded to treatment allocation, after assessing all baseline imaging. INTs were classified into 3 types (I-III) and 2 subtypes (A/B) based on size and if catheter manipulation was likely performed across the vessel territory ostium. Logistic regression was used to understand the effect of multiple a priori identified variables on INT occurrence. Ordinal logistic regression was used to analyze the effect of INTs on modified Rankin Scale shift at 90 days. RESULTS: From 308 patients included, 14 INTs (4.5% overall; 2.8% on follow-up noncontrast computed tomography, 11.7% on follow-up magnetic resonance imaging) were identified (5.0% in endovascular treatment arm versus 4.0% in control arm [P=0.7]). The use of intravenous alteplase was associated with a 68% reduction in the odds of INT occurrence (3.0% with versus 9.1% without; odds ratio, 0.32; 95% confidence interval, 0.11-0.96; adjusted for age, sex, and treatment type). No other variables were associated with INTs. INT occurrence was associated with reduced probability of good clinical outcome (common odds ratio, 0.25; 95% confidence interval, 0.09-0.74; adjusted for age, type of treatment, and follow-up scan). CONCLUSIONS: INTs are uncommon, detected more frequently on follow-up magnetic resonance imaging, and affect clinical outcome. In experienced centers, endovascular treatment is likely not causal, whereas intravenous alteplase may be therapeutic. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Analysis of Workflow and Time to Treatment and the Effects on Outcome in Endovascular Treatment of Acute Ischemic Stroke: Results from the SWIFT PRIME Randomized Controlled Trial.

Purpose To study the relationship between functional independence and time to reperfusion in the Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial in patients with disabling acute ischemic stroke who underwent endovascular therapy plus intravenous tissue plasminogen activator (tPA) administration versus tPA administration alone and to investigate variables that affect time spent during discrete steps. Materials and Methods Data were analyzed from the SWIFT PRIME trial, a global, multicenter, prospective study in which outcomes were compared in patients treated with intravenous tPA alone or in combination with the Solitaire device (Covidien, Irvine, Calif). Between December 2012 and November 2014, 196 patients were enrolled. The relation between time from (a) symptom onset to reperfusion and (b) imaging to reperfusion and clinical outcome was analyzed, along with patient and health system characteristics that affect discrete steps in patient workflow. Multivariable logistic regression was used to assess relationships between time and outcome; negative binomial regression was used to evaluate effects on workflow. The institutional review board at each site approved the trial. Patients provided written informed consent, or, at select sites, there was an exception from having to acquire explicit informed consent in emergency circumstances. Results In the stent retriever arm of the study, symptom onset to reperfusion time of 150 minutes led to 91% estimated probability of functional independence, which decreased by 10% over the next hour and by 20% with every subsequent hour of delay. Time from arrival at the emergency department to arterial access was 90 minutes (interquartile range, 69-120 minutes), and time to reperfusion was 129 minutes (interquartile range, 108-169 minutes). Patients who initially arrived at a referring facility had longer symptom onset to groin puncture times compared with patients who presented directly to the endovascular-capable center (275 vs 179.5 minutes, P < .001). Conclusion Fast reperfusion leads to improved functional outcome among patients with acute stroke treated with stent retrievers. Detailed attention to workflow with iterative feedback and aggressive time goals may have contributed to efficient workflow environments. (©) RSNA, 2016 Online supplemental material is available for this article.

Computed tomography perfusion imaging in the selection of acute stroke patients to undergo emergent carotid endarterectomy.

Severe acute stroke patients with critical carotid stenosis or occlusion without intracranial thrombus typically do not undergo emergent carotid thromboendarterectomy (CEA) because of the risk of reperfusion-related intracranial hemorrhage. Past studies have not consistently demonstrated benefit of early operative intervention. Cerebral computed tomography (CT), cervical and cerebral CT angiography (CTA), and cerebral CT perfusion (CTP) imaging may identify a subset of acute stroke patients without intracranial thrombus who may benefit from emergent CEA. Acute stroke patients underwent unenhanced brain CT imaging to exclude pathology that would contraindicate emergent therapy. Emergent CTAs of the intracranial and extracranial vessels were utilized to identify patients who presented with stroke symptoms based on the presence of isolated extracranial carotid disease in the absence of intracranial thromboembolism. CTP was then used to assess the extent of potentially reversible cerebral ischemia (penumbral tissue). Patients with isolated extracranial carotid lesions with significant reversible ischemia in the absence of large areas of irreversible cerebral damage underwent emergent CEA to salvage ischemic penumbra. In 1 year, 3 patients presented with large acute strokes in which CTA disclosed symptomatic extracranial internal carotid artery preocclusive or occlusive lesions without intracranial thromboembolic occlusions. CTP indicated a large area of ischemic penumbra with limited permanent injury. Mean age, time to presentation, and National Institutes of Health stroke score (NIHSS) were 66 years, 4.2 hr, and 19.3. All patients underwent emergent CEA with cervical carotid thrombectomy. Average time from stroke symptom onset to revascularization was 12.5 (range 5.9-19.0) hr. There were no perioperative deaths. At day 5, the mean NIHSS decreased to 7.6 and at day 30 was 4.7. The modified Rankin scale score dropped from a poststroke, preoperative level of 5 to 2.3 by day 30. Emergent CEA should be considered in patients presenting with large acute strokes based on favorable CT, CTA, and CTP findings. Emergent clot localization and physiological assessment of brain "tissue at risk" relative to irreversible cerebral infarction using CT, CTA, and CTP is now available. Utilization of this information by an experienced stroke team of neurologists, radiologists, and surgeons may aid in the recognition of a select group of patients in which emergent CEA may drive to improved outcomes.