Abstract
Two previous pan-European consensus meetings, the 1995 and 2006 Helsingborg meetings, were convened to review the scientific evidence and the state of current services to identify priorities ...for research and development and to set targets for the development of stroke care for the decade to follow. Adhering to the same format, the European Stroke Organisation (ESO) prepared a European Stroke Action Plan (ESAP) for the years 2018 to 2030, in cooperation with the Stroke Alliance for Europe (SAFE). The ESAP included seven domains: primary prevention, organisation of stroke services, management of acute stroke, secondary prevention, rehabilitation, evaluation of stroke outcome and quality assessment and life after stroke. Research priorities for translational stroke research were also identified. Documents were prepared by a working group and were open to public comments. The final document was prepared after a workshop in Munich on 21–23 March 2018. Four overarching targets for 2030 were identified: (1) to reduce the absolute number of strokes in Europe by 10%, (2) to treat 90% or more of all patients with stroke in Europe in a dedicated stroke unit as the first level of care, (3) to have national plans for stroke encompassing the entire chain of care, (4) to fully implement national strategies for multisector public health interventions. Overall, 30 targets and 72 research priorities were identified for the seven domains. The ESAP provides a basic road map and sets targets for the implementation of evidence-based preventive actions and stroke services to 2030.
The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with ...those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.
The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P<or=0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P<0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration >or=1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.
The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.
The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.
Mechanical thrombectomy using stent retriever devices have been advocated to increase revascularization in intracranial vessel occlusion. We present the results of a large prospective study on the ...use of the Solitaire Flow Restoration in patients with acute ischemic stroke.
Solitaire Flow Restoration Thrombectomy for Acute Revascularization was an international, multicenter, prospective, single-arm study of Solitaire Flow Restoration thrombectomy in patients with large vessel anterior circulation strokes treated within 8 hours of symptom onset. Strict criteria for site selection were applied. The primary end point was the revascularization rate (thrombolysis in cerebral infarction ≥2b) of the occluded vessel as determined by an independent core laboratory. The secondary end point was the rate of good functional outcome (defined as 90-day modified Rankin scale, 0-2).
A total of 202 patients were enrolled across 14 comprehensive stroke centers in Europe, Canada, and Australia. The median age was 72 years, 60% were female patients. The median National Institute of Health Stroke Scale was 17. Most proximal intracranial occlusion was the internal carotid artery in 18%, and the middle cerebral artery in 82%. Successful revascularization was achieved in 79.2% of patients. Device and procedure-related severe adverse events were found in 7.4%. Favorable neurological outcome was found in 57.9%. The mortality rate was 6.9%. Any intracranial hemorrhagic transformation was found in 18.8% of patients, 1.5% were symptomatic.
In this single-arm study, treatment with the Solitaire Flow Restoration device in intracranial anterior circulation occlusions results in high rates of revascularization, low risk of clinically relevant procedural complications, and good clinical outcomes in combination with low mortality at 90 days.
http://www.clinicaltrials.gov. Unique identifier: NCT01327989.
Summary Background Previous studies have suggested that desmoteplase, a novel plasminogen activator, has clinical benefit when given 3–9 h after the onset of the symptoms of stroke in patients with ...presumptive tissue at risk that is identified by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI). Methods In this randomised, placebo-controlled, double-blind, dose-ranging study, patients with acute ischaemic stroke and tissue at risk seen on either MRI or CT imaging were randomly assigned (1:1:1) to 90 μg/kg desmoteplase, 125 μg/kg desmoteplase, or placebo within 3–9 h after the onset of symptoms of stroke. The primary endpoint was clinical response rates at day 90, defined as a composite of improvement in National Institutes of Health stroke scale (NIHSS) score of 8 points or more or an NIHSS score of 1 point or less, a modified Rankin scale score of 0–2 points, and a Barthel index of 75–100. Secondary endpoints included change in lesion volume between baseline and day 30, rates of symptomatic intracranial haemorrhage, and mortality rates. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , NCT00111852. Findings Between June, 2005, and March, 2007, 193 patients were randomised, and 186 patients received treatment: 57 received 90 μg/kg desmoteplase; 66 received 125 μg/kg desmoteplase; and 63 received placebo. 158 patients completed the study. The median baseline NIHSS score was 9 (IQR 6–14) points, and 30% (53 of 179) of the patients had a visible occlusion of a vessel at presentation. The core lesion and the mismatch volumes were small (median volumes were 10·6 cm3 and 52·5 cm3 , respectively). The clinical response rates at day 90 were 47% (27 of 57) for 90 μg/kg desmoteplase, 36% (24 of 66) for 125 μg/kg desmoteplase, and 46% (29 of 63) for placebo. The median changes in lesion volume were: 90 μg/kg desmoteplase 14·0% (0·5 cm3 ); 125 μg/kg desmoteplase 10·8% (0·3 cm3 ); placebo −10·0% (−0·9 cm3 ). The rates of symptomatic intracranial haemorrhage were 3·5% (2 of 57) for 90 μg/kg desmoteplase, 4·5% (3 of 66) for 125 μg/kg desmoteplase, and 0% for placebo. The overall mortality rate was 11% (5% 3 of 57 for 90 μg/kg desmoteplase; 21% 14 of 66 for 125 μg/kg desmoteplase; and 6% 4 of 63 for placebo). Interpretation The DIAS-2 study did not show a benefit of desmoteplase given 3–9 h after the onset of stroke. The high response rate in the placebo group could be explained by the mild strokes recorded (low baseline NIHSS scores, small core lesions, and small mismatch volumes that were associated with no vessel occlusions), which possibly reduced the potential to detect any effect of desmoteplase. Funding PAION Deutschland GmbH; Forest Laboratories.
OBJECTIVETo test the hypothesis that IV thrombolysis (IVT) treatment before endovascular thrombectomy (EVT) is associated with better outcomes in patients with anterior circulation large artery ...occlusion (LAO) stroke, we examined a large real-world database, the Safe Implementation of Treatment in Stroke-International Stroke Thrombectomy Register (SITS-ISTR). METHODSWe identified centers recording ≥10 consecutive patients in the SITS-ISTR, with at least 70% available modified Rankin Scale (mRS) scores at 3 months during 2014 to 2019. We defined LAO as intracranial internal carotid artery, first and second segment of middle cerebral artery, and first segment of anterior cerebral artery. Main outcomes were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial hemorrhage (SICH) per modified SITS-Monitoring Study. We performed propensity score-matched (PSM) and multivariable logistic regression analyses. RESULTSOf 6,350 patients from 42 centers, 3,944 (62.1%) received IVT. IVT + EVT-treated patients had less frequent atrial fibrillation, ongoing anticoagulation, previous stroke, heart failure, and prestroke disability. PSM analysis showed that IVT + EVT-treated patients had a higher rate of functional independence than patients treated with EVT alone (46.4% vs 40.3%, p < 0.001) and a lower rate of death at 3 months (20.3% vs 23.3%, p = 0.035). SICH rates (3.5% vs 3.0%, p = 0.42) were similar in both groups. Multivariate adjustment yielded results consistent with PSM. CONCLUSIONPretreatment with IVT was associated with favorable outcomes in EVT-treated LAO stroke in the SITS-ISTR. These findings, while indicative of international routine clinical practice, are limited by observational design, unmeasured confounding, and possible residual confounding by indication. CLASSIFICATION OF EVIDENCEThis study provides Class II evidence that IVT before EVT increases the probability of functional independence at 3 months compared to EVT alone.
Limited data exist on clot composition and detailed characteristics of arterial thrombi associated with large vessel occlusion in acute ischemic stroke. Advances in endovascular thrombectomy and ...related imaging modalities have created a unique opportunity to analyze thrombi removed from cerebral arteries. Insights into thrombus composition, etiology, physical properties and neurovascular interactions may lead to future advancements in acute ischemic stroke treatment and improved clinical outcomes. Advances in imaging techniques may enhance clot characterization and inform therapeutic decision-making prior to treatment and reveal stroke etiology to guide secondary prevention. Current imaging techniques can provide some information about thrombi, but there remains much to evaluate about relationships that may exist among thrombus composition, occlusion characteristics and treatment outcomes. Improved pathophysiological characterization of clot types, their properties and how these properties change over time, together with clinical correlates from ongoing studies, may facilitate revascularization with thrombolysis and thrombectomy. Interdisciplinary approaches covering clinical, engineering and scientific aspects of thrombus research will be key to advancing the understanding of thrombi and improving acute ischemic stroke therapy. This consensus statement integrates recent research on clots and thrombi retrieved from cerebral arteries and provides a rationale for further analyses, including current opportunities and limitations.
Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient ...populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSS
- NIHSS
= ΔNIHSS
), to examine its relevance to AIS mechanisms and long-term outcomes.
Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced ΔNIHSS
. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS
was examined. Finally, the association of ΔNIHSS
with 90-day favorable outcomes (modified Rankin Scale score 0-2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA).
For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4-16), and median ΔNIHSS
was 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS
(R
=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R
=0.27), but much of the variance remained unexplained. ΔNIHSS
had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS
was similarly associated with 90-day outcomes.
The dynamic phenotype, ΔNIHSS
, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, ΔNIHSS
promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.
Abstract only Introduction: The benefit that endovascular thrombectomy (EVT) offers to stroke patients with large vessel occlusions depends strongly on reperfusion grade as defined by the mTICI ...(modified Thrombolysis in Cerebral Infarction) scale. Our aim was to estimate the public health potential of improved reperfusion. Methods: A Markov model estimated lifetime quality-adjusted life years (QALY) of EVT-treated patients and associated costs based on mTICI grades. The analysis was performed from a United States healthcare perspective. Input parameters were based on best available evidence, including patient data from the HERMES collaboration. The lead analysis was conducted for stroke onset at 65 years. Overall lifetime costs and the net monetary benefit (NMB), which combines weighted QALYs and costs into one composite outcome, were analyzed. A willingness-to-pay threshold of $100,000 per QALY was used for NMB calculations. Results: Lifetime QALYs and the NMB per patient increased for every grade of improved mTICI reperfusion (Fig 1). The final mTICI 2C/3 rate across all trials in the HERMES collaboration was 31%, yielding on average 5.09 QALYs at lifetime costs of $230,799, resulting in a positive NMB of $278,336. Every 10% increase in the final mTICI 2C/3 rate would yield 0.16 incremental QALYs and $16,878 incremental NMB for the average patient. For a national 10% improvement of the mTICI 2C/3 rate of all EVT-treated patients in the United States, we estimated 3,645 additional QALYs and an incremental NMB of $385 million per year. Conclusions: The public health and economic impact of the grade of reperfusion is significant, warranting further improvement of devices and procedural techniques.
The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial ...comparing rivaroxaban versus aspirin in patients with recent ESUS.
We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups.
We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus.
Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe.
NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research.
The purpose of this study was to evaluate safety and efficacy of the Solitaire FR device in the treatment of patients with acute ischemic stroke secondary to large artery occlusion.
We conducted a ...retrospective study of consecutive patients presenting with acute ischemic stroke treated with Solitaire FR as the first-line device to restore blood flow in 6 experienced European centers. This study was entirely funded and supported by Coviden Neurovascular. An independent Corelab determined modified Thrombolysis in Cerebral Infarction scores on the preprocedure and postprocedure angiograms. Complete revascularization was defined as modified Thrombolysis in Cerebral Infarction 2b or 3 post-Solitaire FR device use. Symptomatic intracranial hemorrhage was defined as parenchymal hemorrhage Type 2 associated with a decline of ≥ 4 points in the National Institutes of Health Stroke Scale score within 24 hours or causing death. Favorable functional outcome was considered as modified Rankin Scale score ≤ 2 at Day 90.
We studied 141 patients (mean age, 66 years; median National Institutes of Health Stroke Scale, 18); 74 patients received intravenous tissue-type plasminogen activator before endovascular treatment. Complete revascularization was achieved in 120 of 142 occlusion sites (85%) and good outcome in 77 of 141 (55%) patients. Good outcome was more frequent in patients treated with intravenous tissue-type plasminogen activator than in those without (66% versus 42%; P<0.01). Symptomatic intracranial hemorrhage was reported in 5 patients (4%) and 29 of 141 (20%) patients died or were lost during follow-up (3 cases).
This retrospective study with centralized evaluation shows that the use of Solitaire FR is safe and achieves good revascularization rates and functional outcomes in patients with acute ischemic stroke and large artery occlusion.
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