Summary Background The Solitaire Flow Restoration Device is a novel, self-expanding stent retriever designed to yield rapid flow restoration in acute cerebral ischaemia. We compared the efficacy and ...safety of Solitaire with the standard, predicate mechanical thrombectomy device, the Merci Retrieval System. Methods In this randomised, parallel-group, non-inferiority trial, we enrolled patients from 18 sites (17 in the USA and one in France). Patients were eligible for inclusion if they had acute ischaemic stroke with moderate to severe neurological deficits and were treatable by thrombectomy within 8 h of stroke symptom onset. We used a computer-generated randomisation sequence to randomly allocate patients to receive thrombectomy treatment with either Solitaire or Merci (1:1; block sizes of four and stratified by centre and stroke severity). The primary endpoint was Thrombolysis In Myocardial Ischemia (TIMI) scale 2 or 3 flow in all treatable vessels without symptomatic intracranial haemorrhage, after up to three passes of the assigned device, as assessed by an independent core laboratory, which was masked to study assignment. Primary analysis was done by intention to treat. A prespecified efficacy stopping rule triggered an early halt to the trial. The study is registered with ClinicalTrials.gov , number NCT 01054560. Results Between February, 2010, and February, 2011, we randomly allocated 58 patients to the Solitaire group and 55 patients to the Merci group. The primary efficacy outcome was achieved more often in the Solitaire group than it was in the Merci group (61% vs 24%; difference 37% 95% CI 19–53, odds ratio OR 4·87 95% CI 2·14–11·10; pnon-inferiority <0·0001, psuperiority =0·0001). More patients had good 3-month neurological outcome with Solitaire than with Merci (58% vs 33%; difference 25% 6–43, OR 2·78 1·25–6·22; pnon-inferiority =0·0001, psuperiority =0·02). 90-day mortality was lower in the Solitaire group than it was in the Merci group (17 vs 38; difference −21% –39 to −3, OR 0·34 0·14–0·81; pnon-inferiority =0·0001, psuperiority =0·02). Interpretation The Solitaire Flow Restoration Device achieved substantially better angiographic, safety, and clinical outcomes than did the Merci Retrieval System. The Solitaire device might be a future treatment of choice for endovascular recanalisation in acute ischaemic stroke. Funding Covidien/ev3.
This article reviews recent breakthroughs in the treatment of acute ischemic stroke, mainly focusing on the evolution of endovascular thrombectomy, its impact on guidelines, and the need for and ...implications of next-generation randomized controlled trials.
Endovascular thrombectomy is a powerful tool to treat large vessel occlusion strokes and multiple trials over the past 5 years have established its safety and efficacy in the treatment of anterior circulation large vessel occlusion strokes up to 24 hours from stroke onset.
In 2015, multiple landmark trials (MR CLEAN, ESCAPE, SWIFT PRIME, REVASCAT, and EXTEND IA) established the superiority of endovascular thrombectomy over medical management for the treatment of anterior circulation large vessel occlusion strokes. Endovascular thrombectomy has a strong treatment effect with a number needed to treat ranging from 3 to 10. These trials selected patients based on occlusion location (proximal anterior occlusion: internal carotid or middle cerebral artery), time from stroke onset (early window: up to 6-12 hours), and acceptable infarct burden (Alberta Stroke Program Early CT Score ASPECTS ≥6 or infarct volume <50 mL). In 2017, the DAWN and DEFUSE-3 trials successfully extended the time window up to 24 hours in appropriately selected patients. Societal and national thrombectomy guidelines have incorporated these findings and offer Class 1A recommendation to a subset of well-selected patients. Thrombectomy ineligible stroke subpopulations are being studied in ongoing randomized controlled trials. These trials, built on encouraging data from pooled analysis of early trials (HERMES collaboration) and emerging retrospective data, are studying large vessel occlusion strokes with mild deficits (National Institutes of Health Stroke Scale <6) and large infarct burden (core volume >70 mL).
Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly ...assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis.
We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days.
Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years SD 13·7, 259 51·3% women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76–3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83–3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0–2) than best medical therapy alone (122 45·9% of 266 vs 46 19·3% of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 16·5% of 266 vs 46 19·3% of 238) or symptomatic intracerebral haemorrhage (14 5·3% of 266 vs eight 3·3% of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12–24 h (common OR 5·86 95% CI 3·14–10·94) than those randomly assigned within 6–12 h (1·76 1·18–2·62; pinteraction=0·0087).
These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6–24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6–24 h time window.
Stryker Neurovascular.
Summary Background Present mechanical devices are unable to achieve recanalisation in up to 20–40% of large vessel occlusion strokes. We compared efficacy and safety of the Trevo Retriever, a new ...stent-like device, with its US Food and Drug Administration-cleared predecessor, the Merci Retriever. Methods In this open-label randomised controlled trial, we recruited patients at 26 sites in the USA and one in Spain. We included adults aged 18–85 years with angiographically confirmed large vessel occlusion strokes and US National Institutes of Health Stroke Scale (NIHSS) scores of 8–29 within 8 h of symptom onset. We randomly assigned patients (1:1) with sequentially numbered sealed envelopes to thrombectomy with Trevo or Merci devices. Randomisation was stratified by age (≤68 years vs 69–85 years) and NIHSS scores (≤18 vs 19–29) with alternating blocks of various sizes. The primary efficacy endpoint, assessed by an unmasked core laboratory, was thrombolysis in cerebral infarction (TICI) scores of 2 or greater reperfusion with the assigned device alone. The primary safety endpoint was a composite of procedure-related adverse events. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov , number NCT01270867. Findings Between Feb 3, 2011, and Dec 1, 2011, we randomly assigned 88 patients to the Trevo Retriever group and 90 patients to Merci Retriever group. 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device was used (odds ratio 4·22, 95% CI 1·92–9·69; psuperiority <0·0001). Incidence of the primary safety endpoint did not differ between groups (13 15% patients in the Trevo group vs 21 23% in the Merci group; p=0·1826). Interpretation Patients who have had large vessel occlusion strokes but are ineligible for (or refractory to) intravenous tissue plasminogen activator should be treated with the Trevo Retriever in preference to the Merci Retriever. Funding Stryker Neurovascular.
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.
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).
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).
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.).
Revascularization after endovascular therapy for acute ischemic stroke is measured by the Thrombolysis In Cerebral Infarction (TICI) scale, yet variability exists in scale definitions. We examined ...the degree of reperfusion with the expanded TICI (eTICI) scale and association with outcomes in the HERMES collaboration of recent endovascular trials.
The HERMES Imaging Core, blind to all other data, evaluated angiography after endovascular therapy in HERMES. A battery of TICI scores (mTICI, TICI, TICI2C) was used to define reperfusion of the initial target occlusion defined by non-invasive imaging and conventional angiography.
Angiography of 801 subjects was available, including 797 defined by non-invasive imaging (154 internal carotid artery (ICA), 583 M1, 60 M2) and 748 by conventional angiography (195 ICA, 459 M1, 94 M2). Among 729 subjects in whom the reperfusion grade could be established, using eTICI (3=100%, 2C=90-99%, 2b67=67-89%, 2b50=50-66%) of the conventional angiography target occlusion, there were 63 eTICI 3 (9%), 166 eTICI 2c (23%), 218 eTICI 2b67 (30%), 103 eTICI 2b50 (14%), 100 eTICI 2a (14%), 19 eTICI 1 (3%), and 60 eTICI 0 (8%). Modified Rankin Scale shift analyses from baseline to 90 days showed that increasing TICI grades were linked with better outcomes, with significant distinctions between TICI 0/1 versus 2a (p=0.028), 2a versus 2b50 (p=0.017), and 2b50 versus 2b67 (p=0.014).
The benefit of endovascular therapy in HERMES was strongly associated with increasing degrees of reperfusion defined by eTICI. The eTICI metric identified meaningful distinctions in clinical outcomes and may be used in future studies and routine practice.
Endovascular therapy is increasingly used in acute ischemic stroke treatment and is now considered the gold standard approach for selected patient populations. Prior studies have demonstrated that ...eventual patient outcomes depend on both patient-specific factors and procedural considerations. However, these factors remain unclear for acute basilar artery occlusion stroke. We sought to determine prognostic factors of good outcome in acute posterior circulation large vessel occlusion strokes treated with endovascular therapy.
We reviewed our prospectively collected endovascular databases at 2 US tertiary care academic institutions for patients with acute posterior circulation strokes from September 2005 to September 2015 who had 3-month modified Rankin Scale documented. Baseline characteristics, procedural data, and outcomes were evaluated. A good outcome was defined as a 90-day modified Rankin Scale score of 0 to 2. The association between clinical and procedural parameters and functional outcome was assessed.
A total of 214 patients qualified for the study. Smoking status, creatinine levels, baseline National Institutes of Health Stroke Scale score, anesthesia modality (conscious sedation versus general anesthesia), procedural length, and reperfusion status were significantly associated with good outcomes in the univariate analysis. Multivariate logistic regression indicated that only smoking (odds ratio=2.61; 95% confidence interval, 1.23-5.56;
=0.013), low baseline National Institutes of Health Stroke Scale score (odds ratio=1.09; 95% confidence interval, 1.04-1.13;
<0.0001), and successful reperfusion status (odds ratio=10.80; 95% confidence interval, 1.36-85.96;
=0.025) were associated with good outcome.
In our retrospective case series, only smoking, low baseline National Institutes of Health Stroke Scale score, and successful reperfusion status were associated with good outcome in patients with posterior circulation stroke treated with endovascular therapy.
Background and Purpose- Fast and slow progressors of infarct growth due to anterior circulation large vessel occlusion are commonly observed in clinical practice. We aimed to estimate the prevalence ...and temporal distribution of fast and slow progressors among anterior circulation large vessel occlusion patients diagnosed within 24 hours of stroke onset. Methods- Single-center retrospective study of all patients with anterior circulation large vessel occlusion who underwent baseline computed tomographic perfusion or magnetic resonance imaging within 24 hours of stroke onset. Prevalence was determined for fast progressors (ischemic core >70 mL, <6 hours of stroke onset) and slow progressors (ischemic core ≤30 mL, >6-24 hours of stroke onset). Results- One hundred eighty-five patients were included. The median time interval from stroke onset to baseline core imaging was 7.6 hours (interquartile range, 3.9-13.2), and median core volume was 17 mL (range, 0-405). Patients had core volume ≤70 mL in 72% of cases in the overall cohort. The prevalence of fast progressors was 25% (95% CI, 17%-37%) and reached 40% (95% CI, 24%-59%) between 3 and 4.5 hours after stroke onset. The prevalence of slow progressors was 55% (95% CI, 46%-64%) and was similar across time intervals beyond 6 hours after stroke onset. Conclusions- Most anterior circulation large vessel occlusion patients had small-to-moderate ischemic core volume, irrespective of early or delayed presentation within 24 hours of stroke onset. Fast progressors were highly prevalent between 3 and 4.5 hours after stroke onset.
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