BACKGROUND AND PURPOSE—Frequencies of treatment with r-tPA (recombinant tissue-type plasminogen activator) are increasing over the past 15 years. However, published data on the influence of various ...demographic and clinical factors on r-tPA treatment as well as estimates of future trajectories are limited. We evaluated time trends and future trajectories of r-tPA treatment in patients with acute stroke and the influence of various factors on r-tPA treatment by analyzing data of 103 970 patients enrolled in the Austrian Stroke Unit Registry from 2006 to 2018, of which 18 953 were treated with r-tPA.
METHODS—Time trends of r-tPA-treatment were investigated in predefined subgroups (minor/major stroke, age, anterior/posterior circulation stroke); limited exponential time series models were calculated to estimate future trends of r-tPA-treatment. Logistic regression models were calculated to estimate the influence of clinical variables on r-tPA-treatment.
RESULTS—Overall, r-tPA treatment frequencies increased from 9.9% in 2006 to 21.8% in 2018. We observed a particular increase in patients >80 years, patients presenting with a National Institutes of Health Stroke Scale Score of 2 to 3, patients with posterior circulation stroke, patients with wake-up stroke, and patients without atrial fibrillation. Forecast of overall r-tPA frequencies predicted a further but flattened increase up to 24% by 2025. Logistic regression of time-dependent associations of clinical variables with r-tPA-treatment revealed increasing odds of r-tPA-treatment in patients with a posterior circulation stroke and decreasing odds of r-tPA-treatment in patients with atrial fibrillation.
CONCLUSIONS—We observed a positive development of r-tPA-treatment frequencies mirroring increasing confidence with intravenous thrombolysis in clinical practice; however, decreasing odds of r-tPA-treatment over time in patients with atrial fibrillation deserve particular attention.
Implementation of endovascular treatment for acute stroke due to large vessel occlusion has resulted in a substantial improvement in outcomes after stroke.1 The success of acute stroke treatment is ...highly time dependent.2 Although substantial improvements have been seen in in-hospital workflow,3 the clock starts ticking from time of symptom onset in the prehospital setting. ...prehospital assessment needs to be optimised to enable allocation of the patient to the appropriate hospital—ie, direct transfer to the endovascular thrombectomy-capable centre or transport to the closest primary stroke centre. Notably, in the RACECAT trial (which is based on the RACE score, which performed best in PRESTO), a difference in outcome was not seen for patients directly transferred to the endovascular thrombectomy-capable centre compared with those allocated to a drip-and-ship model.5 Depending on the individual setting and situation, relative travel times between endovascular thrombectomy-capable centres and primary stroke centres will probably affect the optimal workflow of acute stroke care and have a major role in decision-making.6 The bigger challenge for prehospital assessment is patients who do not present with obvious symptoms of severe ischaemic stroke. ...although the performance of some prehospital triage tools seems reasonable,4 it is possible that with expanding candidacy for endovascular thrombectomy and the reducing role of alteplase in patients with large vessel occlusion we could reach a ceiling on prehospital scores.
Background and Purpose:
During the months and years post-stroke, treatment benefits from endovascular therapy (EVT) may be magnified by disability-related differences in morbidity/mortality or may be ...eroded by recurrent strokes and non-stroke-related disability/mortality. Understanding the extent to which EVT benefits may be sustained at 5 years, and the factors influencing this outcome, may help us better promote the sustenance of EVT benefits until 5 years post-stroke and beyond.
Methods:
In this review, undertaken 5 years after EVT became the standard of care, we searched PubMed and EMBASE to examine the current state of the literature on 5-year post-stroke outcomes, with particular attention to modifiable factors that influence outcomes between 3 months and 5 years post-EVT.
Results:
Prospective cohorts and follow-up data from EVT trials indicate that 3-month EVT benefits will likely translate into lower 5-year disability, mortality, institutionalization, and care costs and higher quality of life. However, these group-level data by no means guarantee maintenance of 3-month benefits for individual patients. We identify factors and associated “action items” for stroke teams/systems at three specific levels (medical care, individual psychosocioeconomic, and larger societal/environmental levels) that influence the long-term EVT outcome of a patient. Medical action items include optimizing stroke rehabilitation, clinical follow-up, secondary stroke prevention, infection prevention/control, and post-stroke depression care. Psychosocioeconomic aspects include addressing access to primary care, specialist clinics, and rehabilitation; affordability of healthy lifestyle choices and preventative therapies; and optimization of family/social support and return-to-work options. High-level societal efforts include improving accessibility of public/private spaces and transportation, empowering/engaging persons with disability in society, and investing in treatments/technologies to mitigate consequences of post-stroke disability.
Conclusions:
In the longtime horizon from 3 months to 5 years, several factors in the medical and societal spheres could negate EVT benefits. However, many factors can be leveraged to preserve or magnify treatment benefits, with opportunities to share responsibility with widening circles of care around the patient.
BACKGROUND AND PURPOSE—Posterior circulation stroke (PCS) account for 20% of all ischemic strokes. There is limited evidence whether functional outcome of PCS is comparable to that of anterior ...circulation stroke (ACS). We aimed to analyze whether 3-month functional outcome is different in PCS and ACS.
METHODS—Patients with acute ischemic stroke prospectively enrolled within the Austrian Stroke Unit Registry were stratified by infarct localization according to the Oxfordshire Community Stroke Project Classification. Propensity score matching was used to control for covariate imbalances and to match patients with PCS and ACS. Patients were matched for stroke severity, recombinant tissue-type plasminogen activator treatment, and demographic and vascular risk factors. Main outcomes were the distribution of modified Rankin Scale after 3 months and multiple proportional odds models to estimate the influence of the infarct localization on the functional outcome.
RESULTS—From a total of 90 484 patients enrolled within the Austrian Stroke Unit Registry, 9208 (4604 PCS/4604 ACS) were matched, of those 954 (477 in each group) were treated with recombinant tissue-type plasminogen activator. We detected a significant shift towards better 3-month functional outcome in patients with ACS compared with PCS (odds ratio OR, 1.19; 95% CI, 1.1–1.28; P<0.0001). In particular, functional outcome was worse in PCS with onset-to-door-time >270 minutes (OR, 1.34; 95% CI, 1.17–1.54; P<0.0001) and in PCS with unknown onset-to-door-time (OR, 1.26; 95% CI, 1.13–1.42; P<0.0001); however, we did not detect any difference in functional outcome between ACS and PCS in patients with an onset-to-door-time ≤270 minutes (1–180 minutesOR, 0.92, 95% CI, 0.78–1.09, P=0.3554; 181–270 minutesOR, 1.04, 95% CI, 0.79–1.37, P=0.7689). In patients treated with recombinant tissue-type plasminogen activator, functional outcome was not significantly different between PCS and ACS.
CONCLUSIONS—PCS was associated with worse outcome compared with ACS in patients arriving later than 4.5 hours at hospital or in those with unknown onset of symptoms. Our results urge for implementation of symptoms found in the posterior circulation into preclinical patient-triage tools.
Informed consent is a key concept to ensure patient autonomy in clinical trials and routine care. The coronavirus disease 2019 (COVID-19) pandemic has complicated informed consent processes, due to ...physical distancing precautions and increased physician workload. As such, obtaining timely and adequate patient consent has become a bottleneck for many clinical trials. However, this challenging situation might also present an opportunity to rethink and reappraise our approach to consent in clinical trials. This viewpoint discusses the challenges related to informed consent during the COVID-19 pandemic, whether it could be acceptable to alter current consent processes under these circumstances, and outlines a possible framework with predefined criteria and a system of checks and balances that could allow for alterations of existing consent processes to maximize patient benefit under exceptional circumstances such as the COVID-19 pandemic without undermining patient autonomy.
Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we ...assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke.
For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0–2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0–1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018.
Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0–2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96–1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups.
Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.
Canadian Institutes for Health Research, Alberta Innovates, and NoNO.
and purpose: It is unclear whether intravenous thrombolysis (IVT) outperforms early dual antiplatelet therapy (DAPT) in the acute setting of mild ischemic stroke. The aim of this study was to compare ...early safety and efficacy of IVT to DAPT.
Data of mild non-cardioembolic stroke patients with admission NIHSS <=3 who received IVT or early DAPT in the period 2018-2021 were extracted from a nationwide, prospective stroke unit registry. Study endpoints included symptomatic intracerebral hemorrhage (sICH), early neurological deterioration ≥4 NIHSS points (END), and 3-months functional outcome by modified Rankin Scale (mRS).
1195 mild stroke patients treated with IVT and 2625 treated with DAPT were included. IVT patients were younger (68.1 versus 70.8 years), had less hypertension (72.8% versus 83.5%), diabetes (19% versus 28.8%) and history of myocardial infarction (7.6% versus 9.2%) and slightly higher admission NIHSS scores (median 2 versus median 1) as compared to DAPT patients. After propensity score matching and multivariable adjustment, IVT was associated with sICH (4 (1.2%) vs 0), END (aOR 2.8, CI 1.1-7.5), and there was no difference in mRS 0-1 at 3 months (aOR 1.3, CI 0.7-2.6).
This analysis from a prospective nationwide stroke unit network indicates that IVT is not superior to DAPT in the setting of mild non-cardioembolic stroke and may eventually be associated with harm. Further research focusing on acute therapy of mild stroke is highly warranted.
This study provides Class III evidence that IVT is not superior to dual antiplatelet therapy in patients with acute mild (NIHSS<=3) non-cardioembolic stroke. The study lacks the statistical precision to exclude clinically important superiority of either therapy.
BACKGROUND AND PURPOSE—Embolic stroke of undetermined source (ESUS) constitutes a large proportion of acute ischemic stroke. It is crucial to identify possible stroke etiologies in this patient ...subgroup to individually tailor secondary stroke prevention strategies. This study aimed to assess the prevalence of carotid plaques causing <50% stenosis in ESUS patients on computed tomography angiography and the association of these plaques with ipsilateral strokes.
METHODS—Patients from INTERRSeCT—a multicenter prospective study of patients with acute ischemic stroke—were included in this study if their stroke etiology was not large artery atherosclerosis (>50% stenosis), and neck computed tomography angiography was obtained. Degree of stenosis (<30% versus 30%–50%), maximum plaque thickness, degree of plaque calcification (<50% versus ≥50%), plaque irregularity, ulceration, hypodensity, carotid web, and focal vessel outpouching were assessed for both carotid arteries on computed tomography angiography. Prevalence of carotid plaques with <50% stenosis (nonstenotic plaques), ipsilateral and contralateral to the stroke, in ESUS patients was determined and compared with non-ESUS patients. Features of these plaques with versus without ipsilateral stroke in ESUS patients were compared. Uni- and multivariable logistic regression was performed to determine associations between nonstenotic carotid plaque, plaque characteristics, and ipsilateral stroke in ESUS patients.
RESULTS—Four hundred forty-six patients were included in the study (median age, 73 years; 218 men), 138 of which were ESUS patients (median age, 70 years; 61 men). Nonstenotic carotid plaques (with <50% stenosis) were present in 54 of 138 (39.1%) ESUS patients. Twelve (8.7%) patients had bilateral carotid plaques. Forty (60.6%) of these plaques were ipsilateral and 26 (39.4%) contralateral to the side of the stroke (P=0.004). Nonstenotic carotid plaques were significantly associated with ipsilateral strokes (adjusted odds ratio, 1.83 95% CI, 1.05–3.18).
CONCLUSIONS—In patients with ESUS, nonstenotic carotid plaques were significantly more common on the side of the ischemic stroke, suggesting that these plaques could be a potential stroke etiology in patients in whom the ischemic stroke is classified currently as ESUS.
Abstract only Objective: To determine the prevalence of non-stenotic carotid plaques (<50%) and their association with ipsilateral strokes. Methods: Data was analyzed from the STRATIS registry ...(Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)—a prospective, nonrandomized study of patients undergoing thrombectomy with the Solitaire device. Prevalence of non-stenotic carotid plaques, ipsilateral and contralateral to the stroke was compared in patients with ESUS and cardioembolic strokes. Plaque features were further compared within both subgroups between patients with and without ipsilateral stroke. Uni- and multivariable logistic regression was performed to determine associations between non-stenotic carotid plaque, plaque characteristics, and ipsilateral stroke in both subgroups. Results: Of the 946 patients in the database, 226 patients with cardioembolic stroke (median age, 72 years) and 141 patients with ESUS (median age, 69 years) were included in the analysis.The prevalence of non-stenotic carotid plaque in the cardioembolic and ESUS subgroups was 33/226 (14.6%) and 32/141(22.7%) respectively. Bilateral non-stenotic carotid plaques were seen in 10/226(4.4%) cardioembolic and 13/141(9.2%) ESUS patients. Non-stenotic carotid plaques were significantly associated with ipsilateral strokes in cardioembolic stroke (aOR,1.91 95% CI,1.15-3.18) and in ESUS (aOR,1.69 95% CI, 1.05-2.73). Plaque irregularity, plaque hypodensity and increasing plaque thickness were significantly associated with ipsilateral stroke, only in the ESUS subgroup. Conclusion: Non-stenotic carotid plaques were significantly associated with ipsilateral stroke in cardioembolic and ESUS subgroups and there was increased association of hypodense plaque, increasing plaque thickness and plaque irregularity with ipsilateral stroke in the ESUS subgroup, suggesting these plaques could be a potential cause of stroke in these patient subgroups.
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