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.
Objective
Faster time from onset to recanalization (OTR) in acute ischemic stroke using endovascular therapy (ET) has been associated with better outcome. However, previous studies were based on ...less‐effective first‐generation devices, and analyzed only dichotomized disability outcomes, which may underestimate the full effect of treatment.
Methods
In the combined databases of the SWIFT and STAR trials, we identified patients treated with the Solitaire stent retriever with achievement of substantial reperfusion (Thrombolysis in Cerebral Infarction TICI 2b–3). Ordinal numbers needed to treat values were derived by populating joint outcome tables.
Results
Among 202 patients treated with ET with TICI 2b to 3 reperfusion, mean age was 68 (±13), 62% were female, and median National Institutes of Health Stroke Scale (NIHSS) score was 17 (interquartile range IQR: 14–20). Day 90 modified Rankin Scale (mRS) outcomes for OTR time intervals ranging from 180 to 480 minutes showed substantial time‐related reductions in disability across the entire outcome range. Shorter OTR was associated with improved mean 90‐day mRS (1.4 vs. 2.4 vs. 3.3, for OTR groups of 124‐240 vs. 241‐360 vs. 361‐660 minutes; p < 0.001). The number of patients identified as benefitting from therapy with shorter OTR were 3‐fold (range, 1.5–4.7) higher on ordinal, compared with dichotomized analysis. For every 15‐minute acceleration of OTR, 34 per 1,000 treated patients had improved disability outcome.
Interpretation
Analysis of disability over the entire outcome range demonstrates a marked effect of shorter time to reperfusion upon improved clinical outcome, substantially higher than binary metrics. For every 5‐minute delay in endovascular reperfusion, 1 of 100 patients has a worse disability outcome. Ann Neurol 2015;78:584–593
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.
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).
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.
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.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350.
Summary Background Early results of the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial showed that, by 30 days, 33 (14·7%) of 224 patients ...in the stenting group and 13 (5·8%) of 227 patients in the medical group had died or had a stroke (percentages are product limit estimates), but provided insufficient data to establish whether stenting offered any longer-term benefit. Here we report the long-term outcome of patients in this trial. Methods We randomly assigned (1:1, stratified by centre with randomly permuted block sizes) 451 patients with recent transient ischaemic attack or stroke related to 70–99% stenosis of a major intracranial artery to aggressive medical management (antiplatelet therapy, intensive management of vascular risk factors, and a lifestyle-modification programme) or aggressive medical management plus stenting with the Wingspan stent. The primary endpoint was any of the following: stroke or death within 30 days after enrolment, ischaemic stroke in the territory of the qualifying artery beyond 30 days of enrolment, or stroke or death within 30 days after a revascularisation procedure of the qualifying lesion during follow-up. Primary endpoint analysis of between-group differences with log-rank test was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT 00576693. Findings During a median follow-up of 32·4 months, 34 (15%) of 227 patients in the medical group and 52 (23%) of 224 patients in the stenting group had a primary endpoint event. The cumulative probability of the primary endpoints was smaller in the medical group versus the percutaneous transluminal angioplasty and stenting (PTAS) group (p=0·0252). Beyond 30 days, 21 (10%) of 210 patients in the medical group and 19 (10%) of 191 patients in the stenting group had a primary endpoint. The absolute differences in the primary endpoint rates between the two groups were 7·1% at year 1 (95% CI 0·2 to 13·8%; p=0·0428), 6·5% at year 2 (–0·5 to 13·5%; p=0·07) and 9·0% at year 3 (1·5 to 16·5%; p=0·0193). The occurrence of the following adverse events was higher in the PTAS group than in the medical group: any stroke (59 26% of 224 patients vs 42 19% of 227 patients; p=0·0468) and major haemorrhage (29 13%of 224 patients vs 10 4% of 227 patients; p=0·0009). Interpretation The early benefit of aggressive medical management over stenting with the Wingspan stent for high-risk patients with intracranial stenosis persists over extended follow-up. Our findings lend support to the use of aggressive medical management rather than PTAS with the Wingspan system in high-risk patients with atherosclerotic intracranial arterial stenosis. Funding National Institute of Neurological Disorders and Stroke (NINDS) and others.
Endovascular strategies provide unique opportunity to correlate angiographic measures of collateral circulation at the time of endovascular therapy. We conducted systematic analyses of collaterals at ...conventional angiography on recanalization, reperfusion, and clinical outcomes in the endovascular treatment arm of the Interventional Management of Stroke (IMS) III trial.
Prospective evaluation of angiographic collaterals was conducted via central review of subjects treated with endovascular therapy in IMS III (n=331). Collateral grade before endovascular therapy was assessed with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology scale, blinded to all other data. Statistical analyses investigated the association between collaterals with baseline clinical variables, angiographic measures of recanalization, reperfusion and clinical outcomes.
Adequate views of collateral circulation to the ischemic territory were available in 276 of 331 (83%) subjects. Collateral grade was strongly related to both recanalization of the occluded arterial segment (P=0.0016) and downstream reperfusion (P<0.0001). Multivariable analyses confirmed that robust angiographic collateral grade was a significant predictor of good clinical outcome (modified Rankin Scale score≤2) at 90 days (P=0.0353), adjusted for age, history of diabetes mellitus, National Institutes of Health Stroke Scale strata, and Alberta Stroke Program Early CT Score. The relationship between collateral flow and clinical outcome may depend on the degree of reperfusion.
More robust collateral grade was associated with better recanalization, reperfusion, and subsequent better clinical outcomes. These data, from the largest endovascular trial to date, suggest that collaterals are an important consideration in future trial design.
http://www.clinicaltrials.gov. Unique identifier: NCT00359424.
Collaterals at angiography before endovascular therapy were analyzed to ascertain the effect on a novel end point of successful revascularization without symptomatic hemorrhage in the Solitaire FR ...With the Intention for Thrombectomy (SWIFT) study.
Collateral grade (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology) on baseline angiography was independently assessed, blind to other data, with statistical analyses delineating the relationship with clinical, laboratory, and imaging parameters.
Angiographic data on collaterals were available in 119 of 144 subjects (mean age, 67±12 years; 52% woman; median National Institutes of Health Stroke Scale, 18 range, 8-28). Worse collaterals were noted in subjects with elevated baseline blood glucose (P=0.013) and those with elevated baseline systolic blood pressure (P=0.039). Multivariate predictors of partial or worse collaterals included absence of prior hypertension (odds ratio, 4.049, P=0.012), smoking history (odds ratio, 3.822; P=0.013), and higher blood glucose (odds ratio, 1.017; P=0.022). Collaterals were strongly related to Alberta Stroke Program Early CT Score (ASPECTS) at baseline (0-1: median 8 3-10; 2-9 5-10; 3-9 7-10; 4-9 8-10; P<0.001) and 24 hours (0-1: median 1 0-5; 2-6 0-10; 3-8 0-10; 4-8 4-8; P<0.001). Better collaterals were linked with Thrombolysis in Cerebral Infarction 2b/3 reperfusion (P=0.019), better median National Institutes of Health Stroke Scale at day 7/discharge (P<0.001), and better day 90 modified Rankin Scale (P<0.001). Better collateral grade was associated with successful revascularization without symptomatic hemorrhage, mean 2.3 (95% confidence interval, 2.1-2.5) versus 1.9 (95% confidence interval, 1.7-2.2), P=0.021.
Better collaterals were associated with lower glucose, lower blood pressure, smaller baseline infarcts in SWIFT, and greater likelihood of successful revascularization without hemorrhage and good clinical outcomes.
http://www.clinicaltrials.gov. Unique identifier: NCT01054560.
Intracranial stenosis is one of the most common etiologies of stroke. To our knowledge, no randomized clinical trials have compared balloon-expandable stent treatment with medical therapy in ...symptomatic intracranial arterial stenosis.
To evaluate the efficacy and safety of the balloon-expandable stent plus medical therapy vs medical therapy alone in patients with symptomatic intracranial stenosis (≥70%).
VISSIT (the Vitesse Intracranial Stent Study for Ischemic Stroke Therapy) trial is an international, multicenter, 1:1 randomized, parallel group trial that enrolled patients from 27 sites (January 2009-June 2012) with last follow-up in May 2013.
Patients (N = 112) were randomized to receive balloon-expandable stent plus medical therapy (stent group; n = 59) or medical therapy alone (medical group; n = 53).
a composite of stroke in the same territory within 12 months of randomization or hard transient ischemic attack (TIA) in the same territory day 2 through month 12 postrandomization. A hard TIA was defined as a transient episode of neurological dysfunction caused by focal brain or retinal ischemia lasting at least 10 minutes but resolving within 24 hours. Primary safety measure: a composite of any stroke, death, or intracranial hemorrhage within 30 days of randomization and any hard TIA between days 2 and 30 of randomization. Disability was measured with the modified Rankin Scale and general health status with the EuroQol-5D, both through month 12.
Enrollment was halted by the sponsor after negative results from another trial prompted an early analysis of outcomes, which suggested futility after 112 patients of a planned sample size of 250 were enrolled. The 30-day primary safety end point occurred in more patients in the stent group (14/58; 24.1% 95% CI, 13.9%-37.2%) vs the medical group (5/53; 9.4% 95% CI, 3.1%-20.7%) (P = .05). Intracranial hemorrhage within 30 days occurred in more patients in the stent group (5/58; 8.6% 95% CI, 2.9%-19.0%) vs none in the medical group (95% CI, 0%-5.5%) (P = .06). The 1-year primary outcome of stroke or hard TIA occurred in more patients in the stent group (21/58; 36.2% 95% CI, 24.0-49.9) vs the medical group (8/53; 15.1% 95% CI, 6.7-27.6) (P = .02). Worsening of baseline disability score (modified Rankin Scale) occurred in more patients in the stent group (14/58; 24.1% 95% CI, 13.9%-37.2%) vs the medical group (6/53; 11.3% 95% CI, 4.3%-23.0%) (P = .09).The EuroQol-5D showed no difference in any of the 5 dimensions between groups at 12-month follow-up.
Among patients with symptomatic intracranial arterial stenosis, the use of a balloon-expandable stent compared with medical therapy resulted in an increased 12-month risk of added stroke or TIA in the same territory, and increased 30-day risk of any stroke or TIA. These findings do not support the use of a balloon-expandable stent for patients with symptomatic intracranial arterial stenosis.
clinicaltrials.gov Identifier: NCT00816166.
Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular ...intervention among subgroups needs better definition.
To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke.
We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library without language restriction through August 2015.
Eligible studies were randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, which includes the use of intravenous tissue plasminogen activator (tPA).
Independent reviewers evaluated the quality of studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed subgroup and sensitivity analyses to examine whether certain imaging, patient, treatment, or study characteristics were associated with improved functional outcome. The strength of the evidence was examined for all outcomes using the GRADE method.
Ordinal improvement across modified Rankin scale (mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic revascularization at 24 hours, symptomatic intracranial hemorrhage within 90 days, and all-cause mortality at 90 days.
Data were included from 8 trials involving 2423 patients (mean SD age, 67.4 14.4 years; 1131 46.7% women), including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA. In a meta-analysis of these trials, endovascular therapy was associated with a significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI, 1.14-2.13; P = .005). Functional independence at 90 days (mRS score, 0-2) occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the endovascular therapy group vs 351 of 1094 patients (31.8%; 95% CI, 24.6%-40.0%) in the standard medical care group (risk difference, 12%; 95% CI, 3.8%-20.3%; OR, 1.71; 95% CI, 1.18-2.49; P = .005). Compared with standard medical care, endovascular thrombectomy was associated with significantly higher rates of angiographic revascularization at 24 hours (75.8% vs 34.1%; OR, 6.49; 95% CI, 4.79-8.79; P < .001) but no significant difference in rates of symptomatic intracranial hemorrhage within 90 days (70 events 5.7% vs 53 events 5.1%; OR, 1.12; 95% CI, 0.77-1.63; P = .56) or all-cause mortality at 90 days (218 deaths 15.8% vs 201 deaths 17.8%; OR, 0.87; 95% CI, 0.68-1.12; P = .27).
Among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy vs standard medical care with tPA was associated with improved functional outcomes and higher rates of angiographic revascularization, but no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.
Background and Purpose- We determined the effect of sex on outcome after endovascular stroke thrombectomy in acute ischemic stroke, including lifelong disability outcomes. Methods- We analyzed ...patients treated with the Solitaire stent retriever in the combined SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) cohorts. Ordinal and logistic regression were used to examine known factors influencing outcome after endovascular stroke thrombectomy and study the effect of sex on the association between these factors and outcomes, including age and time to reperfusion. Years of optimal life after thrombectomy were defined as disability-adjusted life years and calculated by projecting disability through adjusted poststroke life expectancy by sex. Results- Among 389 patients treated with endovascular stroke thrombectomy, 55% were females, and median National Institutes of Health Stroke Scale was 17 (interquartile range, 8-28). There were no differences between females versus males in presenting deficit severity (National Institutes of Health Stroke Scale score, 17 versus 17, P=0.21), occlusion location (69% versus 64% M1, P=0.62), presenting infarct extent (Alberta Stroke Program Early CT Score 8 versus 8, P=0.24), rate of substantial reperfusion (Thrombolysis in Cerebral Infarction 2b/3, 87% versus 83%, P=0.37), onset to reperfusion time (294 versus 302 minutes, P=0.46). Despite older ages (69 versus 64, P<0.001) and higher rate of atrial fibrillation (45% versus 30%, P=0.002) for females compared with males, adjusted rates of functional independence at 90 days were similar (odds ratio, 1.0; 95% CI, 0.6-1.6). After adjusting for age at presentation and stroke severity, females had more years of optimal life (disability-adjusted life year) after endovascular stroke thrombectomy, 10.6 versus 8.5 years (P<0.001). Conclusions- Despite greater age and higher rate of atrial fibrillation, females experienced comparable functional outcomes and greater years of optimal life after intervention compared with males.
Large vessel occlusion stroke due to underlying intracranial atherosclerotic disease (ICAD-LVO) is prevalent in 10 to 30% of LVOs depending on patient factors such as vascular risk factors, race and ...ethnicity, and age. Patients with ICAD-LVO derive similar functional outcome benefit from endovascular thrombectomy as other mechanisms of LVO, but up to half of ICAD-LVO patients reocclude after revascularization. Therefore, early identification and treatment planning for ICAD-LVO are important given the unique considerations before, during, and after endovascular thrombectomy. In this review of ICAD-LVO, we propose a multistep approach to ICAD-LVO identification, pretreatment and endovascular thrombectomy considerations, adjunctive medications, and medical management. There have been no large-scale randomized controlled trials dedicated to studying ICAD-LVO, therefore this review focuses on observational studies.
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