Alberta Stroke Program Early Computed Tomography Score to Select Patients for Endovascular Treatment: Interventional Management of Stroke (IMS)-III Trial
Abstract
Background and Purpose—
The Interventional Management of Stroke (IMS)-III trial randomized patients with acute ischemic stroke to intravenous tissue-type plasminogen activator (tPA) plus endovascular therapy versus intravenous tPA therapy alone within 3 hours from symptom onset. A predefined secondary hypothesis was that subjects with significant early ischemic change on the baseline scan would not respond to endovascular therapy.
Methods—
The primary outcome was 90-day modified Rankin Scale score 0 to 2. The baseline and follow-up computed tomographic (CT) scan images were reviewed centrally and blinded to any clinical information. We assessed whether the baseline Alberta Stroke Program Early CT Score (ASPECTS) predicted outcome and interacted with study treatment. We analyzed subgroups defined by time from onset to intravenous tPA initiation and baseline occlusion status at a prespecified α=0.01.
Results—
Baseline demographic and clinical characteristics of 656 randomized patients were similar between subjects with a baseline ASPECTS 8 to 10 (58% of the study sample) versus 0 to 7. Subjects with ASPECTS 8 to 10 were almost twice as likely (relative risk, 1.8; 99% confidence interval, 1.4–2.4) to achieve a favorable outcome. There was insufficient evidence of a treatment-by-ASPECTS interaction. In those treated with onset to intravenous tPA <120 minutes, in CT angiography–proven internal carotid artery or middle cerebral artery occlusion, and in both, results were similar. The probability of achieving recanalization (arterial occlusion lesion, 2–3) of the primary arterial occlusive lesion (relative risk, 1.3; 99% confidence interval, 1.0–1.8) or achieving thrombolysis in cerebral ischemia score 2b/3 reperfusion (relative risk 2.0; 99% confidence interval, 1.2–3.2) was higher among subjects with higher ASPECTS.
Conclusions—
ASPECTS is a strong predictor of outcome and a predictor of reperfusion. ASPECTS did not identify a subpopulation of subjects that particularly benefitted from endovascular therapy immediately after routine intravenous tPA.
Clinical Trial Registration—
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.
Introduction
With technically high-quality noncontrast brain computed tomography (CT), changes of acute ischemia may be observed in a high proportion of patients with major stroke.1,2 Radiological hypoattenuation varies linearly with brain tissue water content and increases linearly with time after middle cerebral artery occlusion and is thus a measure of net water uptake of ischemic brain tissue (ionic edema).3,4 Early ischemic change, scored semiquantitatively using the Alberta Stroke Program Early CT Score (ASPECTS), has been shown to be a strong prognostic factor, equivalent in magnitude of effect to the assessment of clinical stroke severity using the National Institutes of Health Stroke Scale (NIHSS) score.5–8 In 2 studies, a dichotomized ASPECTS (8–10 versus 0–7) has been shown to modify the effect of endovascular thrombolytic therapy.9,10 Only patients with favorable baseline scans (ASPECTS, 8–10) benefitted from endovascular revascularization therapy. The prospective evaluation of baseline CT scans in European Cooperative Acute Stroke Study (ECASS) showed the best treatment response in patients with <1/3 middle cerebral artery territory hypoattenuation (n=215) when compared with patients with normal CT (n=336) and patients with brain tissue hypoattenuation exceeding 1/3 of the middle cerebral artery territory (n=52).2
We assessed the prognostic value of the CT ASPECTS in the Interventional Management of Stroke (IMS)-III study and, in particular, whether response to treatment was different according to the baseline ASPECTS.
Methods
The IMS-III trial was an international, phase III, randomized, open-label with blinded outcome assessment, clinical trial designed to test the approach of intravenous tissue-type plasminogen activator (tPA), started within 3 hours of symptoms onset, followed by protocol-approved endovascular treatment when compared with standard intravenous tPA.11,12 The trial was halted because a futility boundary was crossed at an interim analysis.
At the beginning of the trial, CT angiography (CTA) was infrequently used at participating hospitals to assess the presence of arterial occlusions in patients with acute stroke. Thus, the baseline NIHSS score, a clinical measure of neurological deficit with a range of 0 (no deficit) to 42 (maximum possible deficit), was used to identify those patients (with a score ≥10) and a >80% likelihood of a major arterial occlusion on subsequent angiography after intravenous tPA. In Amendment 3 (April 2009), after 284 participants were randomized, identification of occlusion using CTA was allowed to determine trial eligibility for those participants with NIHSS of 8 or 9 because its routine use increased rapidly during the early course of the study.
CT scans were performed at baseline, at 24±6 hours, and in the setting of neurological decline. A CTA was performed at baseline at those study sites that routinely included CTA in their baseline imaging protocol. CTA was planned for all participants at 24 hours to assess vascular patency. CT scans were acquired using contiguous noncontrast axial 5-mm slices. A minority of CT images were acquired using 10-mm axial slices. The power (kV and mAs) and scan obliquity were not prespecified. All CT scans were acquired within 3 hours of stroke onset. ASPECTS was scored (Methods in the online-only Data Supplement) on all baseline and follow-up CT scans using a 3-people panel consensus method, including a neuroradiologist for all interpretations. The reviewers were blind to all clinical data. Hemorrhage was scored using the Pessin criteria and formalized in the ECASS trials (hemorrhagic infarction, types 1 and 2; parenchymal hematoma, types 1 and 2).13–15
Statistical Methods
The primary clinical outcome was a modified Rankin Scale score of 0 to 2 at 90 days from randomization. Secondary clinical outcomes included the modified Rankin Scale score of 0 to 1 and NIHSS score of 0 to 1 at 90 days from randomization. Recanalization, defined as the arterial occlusion lesion, and reperfusion by the thrombolysis in cerebral ischemia score were secondary surrogate outcome measures. A priori, we divided ASPECTS into 2 groups: favorable (ASPECTS, 8–10) and unfavorable (ASPECTS, 0–7). In addition, we evaluated a third group (ASPECTS, 0–4) that correlates well with the previously defined one third middle cerebral artery rule6 and which defines an ASPECTS trichotomy: ASPECT 8 to 10 as favorable, ASPECTS 5 to 7 as moderately favorable, and ASPECTS 0 to 4 as unfavorable. Data are reported using conventional descriptive statistics, by group. We used an intention-to-treat approach in reporting the outcome data by ASPECTS group. Subjects with missing baseline CT images (n=7) were imputed to have a poor ASPECTS (0–7) score. The CTA subset consisted of those patients who had a routine CTA before enrollment, which defined their location of arterial occlusion pretreatment. For exploratory analyses, we considered the cohort of patients with proven baseline occlusions and with treatment within 2 hours of stroke onset.
Results
Baseline characteristics are shown in Table 1. Baseline demographic and clinical characteristics were similar between subjects with a baseline ASPECTS 8 to 10 (58% of the study sample) versus 0 to 7. There was a gradient of more severe NIHSS scores with more unfavorable ASPECTS and an association between more proximal occlusion location and poorer ASPECTS scores. Thus, clinical stroke severity, vessel occlusion location, and ASPECTS are correlated variables. There was an increased chance of reperfusion at 24 hours with higher ASPECTS. Patients with favorable ASPECTS were more likely to show reperfusion overall (Table 2), but this effect was overcome by endovascular therapy with high rates of recanalization at 24 hours even in the ASPECTS 0 to 4 group.
| ASPECTS 8–10 (n=378) | ASPECTS 0–7 (n=278) | ASPECTS 0–4 (n=92) | |
|---|---|---|---|
| Demographics | |||
| Age (median, IQR) | 70 (17) | 67 (19) | 69 (15.5) |
| Sex (women) % (n) | 49% (187) | 46% (129) | 49% (45) |
| White % (n) | 86% (326) | 82% (228) | 82% (75) |
| Historical variables | |||
| Hypertension % (n) | 76% (288) | 73% (202) | 87% (80) |
| Diabetes mellitus % (n) | 24% (92) | 20% (56) | 21% (19) |
| Atrial fibrillation % (n)* | 32% (122) | 36% (101) | 34% (31) |
| Hyperlipidemia % (n) | 51% (193) | 48% (134) | 50% (46) |
| Current smoker % (n) | 21% (78) | 31% (85) | 34% (31) |
| Congestive heart failure % (n) | 14% (52) | 10% (29) | 11% (10) |
| Peripheral vascular disease % (n) | 7% (28) | 9% (24) | 15% (14) |
| Clinical variables | |||
| NIHSS (median, IQR) | 16 (7) | 18 (7) | 19 (5) |
| Onset-to-IV tPA time, min (median, IQR) | 120 (50) | 120 (47) | 122 (55.5) |
| Onset-to-groin puncture time, min (median, IQR; n=424) | 206.5 (60) | 211 (70) | 214 (80) |
| Glucose, mmol/L (median, IQR) | 6.7 (2.7) | 6.6 (2.3) | 6.7 (1.9) |
| Treatment assignment | |||
| IV+endovascular arm % (n) | 65% (247) | 67% (187) | 62% (57) |
ASPECTS indicates Alberta Stroke Program Early CT Score; IQR, interquartile range; IV, intravenous; NIHSS, National Institutes of Health Stroke Scale; and tPA, tissue-type plasminogen activator.
*
Atrial fibrillation from medical history and baseline ECG.
| ASPECTS 8–10 | ASPECTS 0–7 | ASPECTS 0–4 | ||||
|---|---|---|---|---|---|---|
| Baseline CTA* | (N=154) | (N=128) | (N=40) | |||
| ICA T or L or other ICA occlusion, % (n)† | 16% (24) | 33% (42) | 43% (17) | |||
| M1 occlusion, % (n) | 53% (82) | 52% (67) | 43% (17) | |||
| M2 occlusion, % (n) | 21% (33) | 14% (18) | 13% (5) | |||
| M3 occlusion, % (n/N) | 2% (3) | 1% (1) | 3% (1) | |||
| M4 or distal occlusion, % (n) | 1% (2) | 0% (0) | 0% (0) | |||
| PCA occlusion, % (n) | 2% (3) | ... | ... | |||
| BA/VA occlusion, % (n) | 3% (5) | ... | ... | |||
| Treatment | N=177 | N=129 | N=40 | |||
| IV+endovascular arm % (n) | 67% (119) | 71% (92) | 63% (25) | |||
| Onset-to-IV tPA time (median, IQR) | 120 (54) | 116 (44) | 119 (52) | |||
| Onset-to-groin puncture time (median, IQR; N=210‡ | 208.5 (69) | 202.5 (62) | 210 (71) | |||
| Angiographic outcome (endovascular group only) | ||||||
| AOL recanalization, 3 (% n/N) | 71% (60/84) | 54% (46/85) | 59% (13/22) | |||
| TICI 2b-3 flow (% n/N) | 60% (47/78) | 31% (26/85) | 45% (10/22) | |||
| CTA 24-h vascular outcome | ||||||
| Recanalization (% n/N) | 83% (104/126) | 71% (64/90) | 50% (13/26) | |||
| IV-IA | IV | IV-IA | IV | IV-IA | IV | |
| 87% (73/84) | 74% (31/42) | 88% (42/48) | 56% (9/16) | 73% (11/15) | 18% (2/11) | |
| ICH | ||||||
| Symptomatic | 6% (10/177) | 9% (11/129) | 5% (2/40) | |||
| Asymptomatic | 20% (36/177) | 27% (37/129) | 30% (12/40) | |||
AOL indicates arterial occlusive lesion; ASPECTS, Alberta Stroke Program Early CT Score; BA, basilar artery; CTA, computed tomographic angiography; ICA, internal carotid artery; ICH, intracranial hemorrhage; IQR, interquartile range; IV, intravenous; M1, M1 middle cerebral artery occlusion; M2, M2 branch middle cerebral artery; M3, M3 branch middle cerebral artery; PCA, posterior cerebral artery; TICI, thrombolysis in cerebral ischemia score; tPA, tissue-type plasminogen activator; and VA, vertebral artery.
*
Twenty-three cases in ASPECTS 8–10 were missing CTA adjudication of the baseline occlusion site and 1 case in the ASPECTS 0–7 group.
†
Does not include proximal ICA occlusions.
‡
One subject randomized to IV who underwent acute endovascular treatment.
The treatment effect was not modified by the dichotomized ASPECTS (P=0.871). Because the study did not show benefit of 1 treatment arm compared with the other and both groups had active treatment, effect modification, as a secondary analysis, would a priori be difficult to demonstrate unless there was a clear qualitative interaction with counterbalanced effects in each group. However, the direction of effect for endovascular therapy, although imprecise because of the small sample size, was toward fewer good outcomes among patients with unfavorable baseline CT scans (ASPECTS, 0–4), similar to the analysis undertaken for IMS-1.10 Among patients with favorable scans, a directional trend to a greater treatment effect was observed among patients treated earlier and with proven arterial occlusions (Table I and Figure I in the online-only Data).
Irrespective of treatment modality, ASPECTS was a strong prognostic variable. A favorable scan conferred a 2-fold or greater chance of an independent functional outcome (Table 3). This result was unchanged after multivariable adjustment. Similar to the above, the direction of effect showed a larger effect size among patients treated earlier and with proven arterial occlusions (Table 3). Remarkably, some 20% of patients with highly unfavorable scans (ASPECTS, 0–4) achieved an independent functional outcome (Table 4).
| ASPECTS 8–10 | ASPECTS 0–7 | RR (CI99) | ASPECTS 0–4 | |
|---|---|---|---|---|
| ITT population | n=378 | n=278 | n=92 | |
| mRS 0–2 at 90 d, % (n) | 49% (187) | 27% (76) | 1.8 (1.4–2.4) | 21% (19) |
| mRS 0–1 at 90 d, % (n) | 34% (130) | 18% (50) | 1.9 (1.3–2.8) | 12% (11) |
| NIHSS 0–1 at 90 d, % (n) | 33% (123) | 17% (47) | 1.9 (1.3–2.8) | 7% (6) |
| Onset-to-IV tPA time ≤120 min | n=202 | n=143 | n=45 | |
| mRS 0–2 at 90 d, % (n) | 50% (101) | 29% (42) | 1.7 (1.2–2.5) | 29% (13) |
| mRS 0–1 at 90 d, % (n) | 34% (69) | 22% (31) | 1.6 (1.0–2.5) | 20% (9) |
| NIHSS 0–1 at 90 d, % (n) | 35% (71) | 21% (30) | 1.7 (1.0–2.7) | 11% (5) |
| Baseline ICA and M1-MCA occlusion on CTA | n=106 | n=109 | n=34 | |
| mRS 0–2 at 90 d, % (n) | 57% (60) | 25% (27) | 2.3 (1.4–3.7) | 15% (5) |
| mRS 0–1 at 90 d, % (n) | 40% (42) | 14% (15) | 2.9 (1.4–5.7) | 6% (2) |
| NIHSS 0–1 at 90 d, % (n) | 39% (41) | 16% (17) | 2.5 (1.3–4.8) | 3% (1) |
| Onset-IV tPA time ≤120 min and baseline ICA and M1-MCA occlusion on CTA | n=57 | n=65 | n=17 | |
| mRS 0–2 at 90 d, % (n) | 61% (35) | 25% (16) | 2.5 (1.3–4.6) | 12% (2) |
| mRS 0–1 at 90 d, % (n) | 44% (25) | 17% (11) | 2.6 (1.2–5.8) | 12% (2) |
| NIHSS 0–1 at 90 d, % (n) | 44% (25) | 20% (13) | 2.2 (1.0–4.6) | 6% (1) |
| Baseline ICA and MCA (M1–M4) occlusion on CTA | n=144 | n=128 | n=40 | |
| mRS 0–2 at 90d, % n | 54% (78) | 29% (37) | 1.9 (1.2–2.8) | 20% (8) |
| mRS 0–1 at 90d, % n | 39% (56) | 16% (20) | 2.5 (1.4–4.5) | 5% (2) |
| NIHSS 0–1 at 90d, % n | 36% (52) | 16% (21) | 2.2 (1.2–4.0) | 3% (1) |
| Onset-IV tPA time ≤120 min and baseline ICA and MCA (M1–M4) occlusion on CTA | n=76 | n=74 | n=21 | |
| mRS 0–2 at 90 d, % (n) | 61% (46) | 31% (23) | 1.9 (1.2–3.2) | 24% (5) |
| mRS 0–1 at 90 d, % (n) | 46% (35) | 19% (14) | 2.4 (1.2–4.9) | 10% (2) |
| NIHSS 0–1 at 90 d, % (n) | 43% (33) | 20% (15) | 2.1 (1.1–4.2) | 5% (1) |
AOL indicates arterial occlusive lesion; ASPECTS, Alberta Stroke Program Early CT Score; BA, basilar artery; CI99, 99% confidence interval; CTA, computed tomographic angiography; ICA, internal carotid artery; ICH, intracranial hemorrhage; ITT, intention-to-treat; IV, intravenous; M1, M1 middle cerebral artery occlusion; M2, M2 branch middle cerebral artery; M3, M3 branch middle cerebral artery; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; PCA, posterior cerebral artery; RR, relative risk; and tPA, tissue-type plasminogen activator.
| mRS 0–2 | mRS 3–6 | |
|---|---|---|
| Demographics | n=19 | n=73 |
| Age (median, IQR) | 63 (22) | 70 (15) |
| Sex (women), % (n) | 42% (8) | 51% (37) |
| White, % (n) | 84% (16) | 81% (59) |
| Historical variables | ||
| Hypertension, % (n) | 89% (17) | 86% (63) |
| Diabetes mellitus, % (n) | 11% (2) | 23% (17) |
| Atrial fibrillation, % (n) | 47% (9) | 30% (22) |
| Hyperlipidemia, % (n) | 58% (11) | 48% (35) |
| Current smoker, % (n) | 37% (7) | 33% (24) |
| Congestive heart failure, % (n) | 11% (2) | 11% (8) |
| Peripheral vascular disease, % (n) | 16% (3) | 15% (11) |
| Clinical variables | ||
| NIHSS (median, IQR) | 16 (8) | 19 (4) |
| Onset-to-IV tPA time (median, IQR) | 115 (32) | 125 (56) |
| Onset-to-groin puncture time (median, IQR) | 196 (80) | 215 (70) |
| Glucose, mmol/L (median, IQR) | 6.3 (1.1) | 6.9 (1.9) |
| Affected hemisphere on baseline imaging | ||
| Left hemisphere | 26% (5) | 27% (20) |
| Right hemisphere | 58% (11) | 70% (51) |
| Unknown/multiple | 5% (1) | 0% (0) |
| No acute occlusion | 11% (2) | 3% (2) |
| Treatment assignment | ||
| IV+endovascular arm, % (n) | 58% (11) | 63% (46) |
| Safety events | ||
| Symptomatic ICH | 0% (0) | 7% (5) |
ASPECTS indicates Alberta Stroke Program Early CT Score; ICH, intracranial hemorrhage; IQR, interquartile range; IV, intravenous; mRS, modified Rankin Scale score; NIHSS, National Institutes of Health Stroke Scale; TICI, thrombolysis in cerebral ischemia score; and tPA, tissue-type plasminogen activator.
Discussion
ASPECTS is a measure of imaging-defined ischemic injury to the brain that is a strong and consistent predictor of clinical outcome. Although previous smaller studies of endovascular therapy, a retrospective analysis of the Prolyse in Acute Cerebral Thromboembolism (PROACT)-2 study and a historically controlled analysis of IMS-1,9,10 and prior intravenous thrombolysis studies,13 showed evidence of effect modification (a multiplicative interaction) between favorable ASPECTS (score, 8–10) and good clinical outcome, this was not demonstrated in our study. Subjects with low ASPECTS scores benefitted far less in IMS-III and this observation, consistent with prior trials of thrombolysis,9,10 supports the concept of non-nutritive, futile, or even harmful reperfusion. Reperfusing dead brain is simply unhelpful to acute neurological recovery. Although reliable and pragmatic imaging biomarkers for patient selection continue to be sought, these data do not convincingly support the use of noncontrast CT ASPECTS in isolation to select patients for an intravenous plus endovascular approach to therapy.
There are multiple limitations in the assessment of potential ASPECTS-by-treatment interactions, in the search for an imaging-defined biomarker that helps select patients for treatment. These are generalizable in varying degree to other imaging modalities (including CTP and multimodal MR) and other potential biomarkers.
First, measurement error is underappreciated. The reliability of ASPECTS interpretation is moderate within 90 minutes of stroke onset, good between 90 and 180 minutes, and excellent beyond that.1,16 There are subtleties of interpretation, which may result in situations where a patient with an apparently unfavorable scan does well. Patients with unfavorable ASPECTS at baseline may do well if the infarcts are located in tolerant regions of brain, such as the right temporal lobe; there is a real-estate effect. In addition, patients may do well despite a large infarction if the capacity for regeneration, adaptation, and recovery is exceptional.
Second, reperfusion therapy has only worked part of the time. Although reperfusion rates were relatively high at 24 hours in IMS-III, the reperfusion rates early after treatment (1–4 hours) were not defined for the intravenous tPA-only group. The quality and proportional recanalization in the endovascular arm (measured using the thrombolysis in cerebral ischemia scoring system) were poor. Thus, the relationship between outcome and pretreatment ASPECTS continues to be confounded by variability in treatment response.
Third, the baseline scan is a snapshot in time that reflects a physiological state only for a short period of time; the scan has a shelf-life and consequently the shorter the time interval from CT scan to reperfusion, the stronger the potential predictive value of ASPECTS.17 In future studies, it will be critical to measure the picture-to-puncture and picture-to-reperfusion times.18 In IMS-III, the average time to treatment was long, during which time infarction progressed. Therefore, time to reperfusion is a related confounding variable.
Finally, most studies, including this one, are underpowered to assess for interaction effects. All of these issues applied less to the PROACT-2 analysis,9 which did show evidence of interaction. Key differences between PROACT-2 and IMS-III were the much later onset-to-treatment time and the large difference in reperfusion rates between the 2 treatment groups in PROACT-2 when compared with IMS-III.12,19
There is strong biological evidence that a low ASPECTS score implies a poor outcome irrespective of treatment. Consistent with past reports, a favorable ASPECTS predicted good outcome. Interestingly, patients with favorable ASPECTS were also more likely to recanalize and reperfuse. The stroke itself may be impacting defensive vascular mechanisms that are designed to restore blood flow in the brain. Favorable ASPECTS is associated with good collateral blood flow allowing ischemic brain tissue to survive for longer time periods and enabling intravenous thrombolytics to attack the thrombus from both sides.20–22 Moreover, higher ASPECTS may be associated with more distal arterial occlusions with smaller sized thrombi when compared with the proximal occlusion of major cerebral arteries. Intriguingly, we did observe that about one fifth of patients with highly unfavorable scans (ASPECTS, 0–4) achieved a good functional clinical outcome. We attribute this finding to a linear combination of lower age, faster treatment, lower baseline stroke severity, lower baseline serum glucose, higher number of no baseline occlusion cases, and fewer symptomatic intracranial hemorrhage occurrences as principal reasons for good outcome in this group (Table 4).
One limitation of our data was the imaging itself. Qualitatively, we found significant variability in image quality related to age of the CT scanner, helical versus sequential scan acquisition, scanning energy used (keV and mAs settings), scanner-type image reconstruction algorithms, including iterative reconstruction. Older scanners, helical image acquisition, lower scanning energy, and nonoptimized image reconstruction algorithms were associated with much poorer image contrast between gray and white matter. Optimizing CT scanner parameters may substantially improve measurement issues at an individual site.
Overall, ASPECTS is a strong prognostic variable. Until we can treat all patients quickly with 80% to 90% thrombolysis in cerebral ischemia-3 flow, we will not be able to understand the degree to which baseline imaging—using ASPECTS—is a useful method to select patients for combined intravenous thrombolysis immediately followed by endovascular therapy.
Acknowledgments
Dr Hill wrote the first draft of the article. Dr Palesch, Dr Yeatts, and L.D. Foster performed statistical analysis. Drs Broderick and Tomsick are the principal investigators for the Interventional Management of Stroke (IMS)-III study. Drs Demchuk and Goyal are the principals for the core imaging laboratory. Dr Jovin is a member of the IMS-III Executive Committee and has reviewed the article. Dr von Kummer is principal investigator for IMS-III in Europe and reviewed the article. All authors provided key roles in study design, execution data collection, analysis, and interpretation of the study results.
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The image is taken from an article in this issue, “Evaluating Intracranial Atherosclerosis Rather Than Intracranial Stenosis” by Leng et al (Stroke. 2014;45:645�651). The image is 2B and 2C.
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© 2013 American Heart Association, Inc.
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History
Received: 24 September 2013
Revision received: 21 October 2013
Accepted: 31 October 2013
Published online: 12 December 2013
Published in print: February 2014
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Disclosures
Dr von Kummer is a consultant to Lundbeck AC and Penumbra Inc. Dr Goyal has received honouraria for speaking from Covidien EV3. Dr Jovin is a consultant to Silk Road Medical. Dr Demchuk is a consultant to Covidien EV3. Dr Broderick has is a consultant to Genentech Ltd, Schering Plough, EKOS Corp. Dr Hill has been a consultant to Covidien EV3. The other authors report no conflicts.
Sources of Funding
This study was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke grant numbers: Univeristy of Cincinnati U01NS052220; Medical University of South Carolina U01NS054630. Genentech Inc supplied study drug used for intra-arterial tissue-type plasminogen activator in the Endovascular group. EKOS Corp, Concentric Inc, Cordis Neurovascular, Inc supplied study catheters during Amendments 1 to 3. In Europe, Interventional Management of Stroke-III Investigator meeting support was provided in part by Boehringer Ingelheim.
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- Mechanical thrombectomy after 6 hours from the symptoms onset in acute ischemic stroke in the carotid basin due to the large vessel occlusion, Ukrainian Interventional Neuroradiology and Surgery, 45, 3, (16-26), (2023).https://doi.org/10.26683/2786-4855-2023-3(45)-16-26
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