Risk of stroke in patients with prior VKA or DOAC: A population-based real-world registry analysis.

INTRODUCTION: To date, risk assessment of suffering ischemic and hemorrhagic stroke in individuals under oral anticoagulation (OAC) is limited to hospital-based cohorts and patients with atrial fibrillation. PATIENTS AND METHODS: Through the combination of three individual datasets, (1) the population-based Tyrolean Stroke Pathway database, prospectively documenting all (unselected) stroke patients in the entire federal state of the Tyrol and (2) nation-wide prescription data, detailing each reimbursed prescription in Austria as well as (3) the Austrian Stroke Unit Registry, a nation-wide registry comprising data on all patients admitted to any of the 38 stroke units in Austria, we assessed risk of stroke in patients with prior oral anticoagulation and compared characteristics of patients taking direct oral anticoagulants and Vitamin-K-Antagonists. RESULTS: In Austria, oral anticoagulant prescription reimbursements increased from 292,475 in 2015 to 389,407 in 2021. In the Tyrol, prior oral anticoagulation treatment was evident in 586 of 3861 (15.2%) patients with ischemic and 131 of 523 (25.0%) with hemorrhagic stroke, with 20% and 35% of those stroke patients respectively having prior oral anticoagulation due to other indications than non-valvular atrial fibrillation. Considering prescription rates, treatment with direct oral anticoagulants was associated with a reduced stroke risk compared to Vitamin-K-Antagonists, especially in ischemic (1.05% vs 0.62%; RR 0.59, p < 0.001) but also in hemorrhagic stroke, even if less pronounced (0.21% vs 0.14%; RR 0.68, p = 0.06). In Austria, prior intake of direct oral anticoagulants was associated with lower risk of suffering acute large vessel occlusion stroke (RR 0.79, p = 0.003). DISCUSSION AND CONCLUSIONS: One in seven patients suffering ischemic and one in four suffering hemorrhagic stroke had prior oral anticoagulation treatment. Both ischemic and hemorrhagic strokes are less frequent in those with direct oral anticoagulant intake compared to those taking Vitamin-K-Antagonists. Establishment of clear standard operating procedures on how to best care for acute stroke patients with oral anticoagulation is essential.

IV Thrombolysis vs Early Dual Antiplatelet Therapy in Patients With Mild Noncardioembolic Ischemic Stroke.

BACKGROUND OBJECTIVES: It is unclear whether IV thrombolysis (IVT) outperforms early dual antiplatelet therapy (DAPT) in the acute setting of mild ischemic stroke. The aim of this study was to compare the early safety and efficacy of IVT with that of DAPT. METHODS: Data of mild noncardioembolic stroke patients with admission NIH Stroke Scale (NIHSS) score ≤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 neurologic deterioration ≥4 NIHSS points (END), and 3-month functional outcome by modified Rankin scale (mRS). RESULTS: A total of 1,195 mild stroke patients treated with IVT and 2,625 patients treated with DAPT were included. IVT patients were younger (68.1 vs 70.8 years), had less hypertension (72.8% vs 83.5%), diabetes (19% vs 28.8%), and a history of myocardial infarction (7.6% vs 9.2%), and slightly higher admission NIHSS scores (median 2 vs median 1) when compared with DAPT patients. After propensity score matching and multivariable adjustment, IVT was associated with sICH (4 [1.2%] vs 0) and END (adjusted odds ratio [aOR] 2.8, 95% CI 1.1-7.5), and there was no difference in mRS 0-1 at 3 months (aOR 1.3, 95% CI 0.7-2.6). DISCUSSION: This analysis from a prospective nationwide stroke unit network indicates that IVT is not superior to DAPT in the setting of mild noncardioembolic stroke and may eventually be associated with harm. Further research focusing on acute therapy of mild stroke is highly warranted. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that IVT is not superior to DAPT in patients with acute mild (NIHSS score ≤3) noncardioembolic stroke. The study lacks the statistical precision to exclude clinically important superiority of either therapy.

Endovascular stroke therapy outside core working hours in a nationwide stroke system.

BACKGROUND: Endovascular therapy (EVT) has been established as a major component in the acute treatment of large vessel occlusion stroke. However, it is unclear whether outcome and other treatment-related factors differ if patients are treated within or outside core working hours. METHODS: We analyzed data from the prospective nationwide Austrian Stroke Unit Registry capturing all consecutive stroke patients treated with EVT between 2016 and 2020. Patients were trichotomized according to the time of groin puncture into treatment within regular working hours (08:00-13:59), afternoon/evening (14:00-21:59) and night-time (22:00-07:59). Additionally, we analyzed 12 EVT treatment windows with equal patient numbers. Main outcome variables included favorable outcome (modified Rankin Scale scores of 0-2) 3 months post-stroke as well as procedural time metrics, recanalization status and complications. RESULTS: We analyzed 2916 patients (median age 74 years, 50.7% female) who underwent EVT. Patients treated within core working hours more frequently had a favorable outcome (42.6% vs 36.1% treated in the afternoon/evening vs 35.8% treated at night-time; p=0.007). Similar results were found when analyzing 12 treatment windows. All these differences remained significant in multivariable analysis adjusting for outcome-relevant co-factors. Onset-to-recanalization time was considerably longer outside core working hours, which was mainly explained by longer door-to-groin time (p<0.001). There was no difference in the number of passes, recanalization status, groin-to-recanalization time and EVT-related complications. CONCLUSIONS: The findings of delayed intrahospital EVT workflows and worse functional outcomes outside core working hours in this nationwide registry are relevant for optimization of stroke care, and might be applicable to other countries with similar settings.

Pre-hospital and intrahospital workflow optimization for patients with suspected ischemic stroke due to large vessel occlusion - findings from a tertiary care facility.

BACKGROUND: The efficacy of recanalization treatment in patients with ischemic stroke due to large vessel occlusion (LVO) is highly time dependent. We aimed to investigate the effects of an optimization of prehospital and intrahospital pathways on time metrics and efficacy of endovascular treatment in ischemic stroke due to LVO. METHODS: Patients treated with mechanical thrombectomy (MT) at the Hospital of St. John of God Vienna, Austria, between 2013 and 2020 were extracted from the Austrian Stroke Unit Registry. Study endpoints including time metrics, early neurological improvement and functional outcome measured by modified Rankin Scale (mRS) at 3 months were compared before and after optimization of prehospital and intrahospital pathways. RESULTS: Two hundred ninety-nine patients were treated with MT during the study period, 94 before and 205 after the workflow optimization. Workflow optimization was significantly associated with time metrics improvement (door to groin puncture time 45 versus 31 min; p < 0.001), rates of neurological improvement (NIHSS ≥ 8: 30 (35%) vs. 70 (47%), p = 0.04) and radiological outcome (TICI ≥ 2b: 71 (75%) versus 153 (87%); p = 0.013). Functional outcome (mRS 0-2: 17 (18%) versus 57 (28%); p = 0.067) and mortality (34 (37%) versus 54 (32%); p = 0.450) at 3 months showed a non-significant trend in the later time period group. CONCLUSION: The implementation of workflow optimization was associated a significant reduction of intrahospital time delays and improvement of neurological and radiological outcomes.

CT- versus MRI-Based Imaging for Thrombolysis and Mechanical Thrombectomy in Ischemic Stroke: Analysis from the Austrian Stroke Registry.

BACKGROUND AND PURPOSE: It is unclear whether a particular stroke imaging modality offers an advantage for the acute stroke treatment. The aim of this study was to compare procedure times, efficacy and safety of thrombolysis and/or thrombectomy based on computed tomography (CT) versus magnetic resonance imaging (MRI) acute stroke imaging. METHODS: Data of stroke patients who received intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) were extracted from a nationwide, prospective stroke unit registry and categorized according to initial imaging modality. Study endpoints included procedure times, symptomatic intracerebral hemorrhage (sICH), early neurological improvement, 3-month functional outcome by modified Rankin Scale (mRS) and mortality. RESULTS: Stroke patients (n=16,799) treated with IVT and 2,248 treated with MT were included. MRI-guided patients (n=2,599) were younger, had less comorbidities and higher rates of strokes with unknown onset as compared to CT-guided patients. In patients treated with IVT, no differences were observed regarding the rates of functional outcome by mRS 0-1 (adjusted odds ratio [OR], 0.87; 95% confidence interval [CI], 0.71 to 1.05), sICH (adjusted OR, 0.82; 95% CI, 0.61 to 1.08), and mortality (adjusted OR, 0.88; 95% CI, 0.63 to 1.22). Patients undergoing MT selected by MRI as compared to CT showed equal rates of functional outcome by mRS 0-2 (adjusted OR, 0.87; 95% CI, 0.65 to 1.16), sICH (adjusted OR, 0.9; 95% CI, 0.51 to 1.69), and mortality (adjusted OR, 0.62; 95% CI, 0.35 to 1.09). MRI-guided patients showed a significant intrahospital delay of about 20 minutes in both the IVT and the MT group. CONCLUSIONS: This large non-randomized comparison study indicates that CT- and MRI-guided patient selection for IVT/MT may perform equally well in terms of functional outcome and safety.

Mechanical Thrombectomy in Acute Stroke Patients with Moderate to Severe Pre-Stroke Disability.

BACKGROUND AND PURPOSE: Studies on mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with preexisting disability are limited. We aimed to compare the outcomes of MT versus best medical treatment (BMT) in these patients. METHODS: In the nationwide Austrian registry and Swiss monocentric registry, we identified 462 AIS patients with pre-stroke disability (modified Rankin Scale [mRS] score ≥3) and acute large vessel occlusion. The primary outcome was returning to pre-stroke mRS or better at 3 months. Secondary outcomes were early neurological improvement (National Institutes of Health Stroke Scale score improvement ≥8 at 24 to 48 hours), 3-month mortality, and symptomatic intracerebral hemorrhage (sICH). Multivariable regression models and propensity score matching (PSM) were used for statistical analyses. RESULTS: Compared with the BMT group (n=175), the MT group (n=175) had younger age, more severe strokes, and lower pre-stroke mRS, but similar proportion of receiving intravenous thrombolysis. MT was associated with higher odds of returning to baseline mRS or better at 3 months (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI], 1.39 to 4.47), early neurological improvement (aOR, 2.62; 95% CI, 1.41 to 4.88), and lower risk of 3-month mortality (aOR, 0.29; 95% CI, 0.18 to 0.49). PSM analysis showed similar findings. MT was not associated with an increased risk of sICH (4.0% vs. 2.1% in all patients; 4.2% vs. 2.4% in the PSM cohort). CONCLUSIONS: MT in patients with pre-stroke mRS ≥3 might improve the 3-month outcomes and short-term neurological impairment, suggesting that pre-stroke disability alone should not be a reason to withhold MT, but that individual case-by-case decisions may be more appropriate.

Long-term outcome of a pragmatic trial of multifaceted intervention (STROKE-CARD care) to reduce cardiovascular risk and improve quality-of-life after ischaemic stroke and transient ischaemic attack: study protocol.

BACKGROUND: Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of incident cardiovascular events and recurrent stroke. Despite compelling evidence about the efficacy of secondary prevention, a substantial gap exists between risk factor management in real life and that recommended by international guidelines. We conducted the STROKE-CARD trial (NCT02156778), a multifaceted pragmatic disease management program between 2014 and 2018 with follow-up until 2019. This program successfully reduced cardiovascular risk and improved health-related quality of life and functional outcome in patients with acute ischaemic stroke or TIA within 12 months after the index event. To investigate potential long-term effects of STROKE-CARD care compared to standard care, an extension of follow-up is warranted. METHODS: We aim to include all patients from the STROKE-CARD trial (n = 2149) for long-term follow-up between 2019 and 2021 with the study visit scheduled 3-6 years after the stroke/TIA event. The co-primary endpoint is the composite of major recurrent cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, and vascular death) from hospital discharge until the long-term follow-up visit and health-related quality of life measured with the European Quality of Life-5 Dimensions (EQ-5D-3L) at the final visit. Secondary endpoints include overall mortality, long-term functional outcome, and target-level achievement in risk factor management. DISCUSSION: This long-term follow-up will provide evidence on whether the pragmatic post-stroke/TIA intervention program STROKE-CARD is capable of preventing recurrent cardiovascular events and improving quality-of-life in the long run. Trial registration clinicaltrials.gov: NCT04205006 on 19 December 2019.

Time trends in stroke severity in the years 2005 to 2020: results from the Austrian Stroke Unit Registry.

BACKGROUND AND PURPOSE: With aging population, there is an increase of atrial fibrillation (AF) and other vascular risk factors. We investigated trends in stroke severity at hospital admission with respect to AF and other risk factors in a prospective national stroke registry from 2005 to 2020. METHODS: Data from the prospective Austrian Stroke Unit Registry were used to study demographic and clinical factors associated with the change in admission stroke severity over years. Time trends in admission stroke severity of patients with pre-stroke modified Rankin Score ≤ 3 were investigated with respect to clinical variables and predefined age groups 18-54, 55-64, 65-74, 75-84 and ≥ 85 years. Time trends were studied using robust generalized linear models assuming normal distribution with a log link. Stroke severity on admission was assessed according to the National Institutes of Health Stroke Scale Score (NIHSS). RESULTS: In total, 140,312 patients with acute ischemic stroke were included in the analysis. Within the study period, mean patients' age increased from 70 to 72 years (p < 0.001) and median NIHSS at admission decreased from 4 to 3 (p < 0.001). The frequency of AF increased from 25 to 32% (p < 0.001). The decrease in median admission NIHSS was evident in all relevant subgroups but more pronounced in patients with risk factors including AF, diabetes, hypercholesterolemia, smoking, elderly patients and those with pre-stroke disability. CONCLUSION: Despite an aging population and generally increasing AF frequency, we observed a consistent trend towards less disabling strokes on admission.

Intravenous thrombolysis in stroke with admission NIHSS score 0 or 1.

BACKGROUND: Up to 30% of stroke patients initially presenting with non-disabling or mild deficits may experience poor functional outcome. Despite, intravenous thrombolysis remains controversial in this subgroup of stroke patients due to its uncertain risk benefit ratio. AIM: We aimed to analyze the real-world experience with intravenous thrombolysis in stroke patients presenting with very low NIHSS. METHODS: Data of stroke patients presenting with mild initial stroke severity (NIHSS 0-5) including vascular risk factors, stroke syndrome and etiology, early neurological deterioration, symptomatic intracerebral haemorrhage (sICH), and functional outcome by modified Rankin Scale were extracted from a large nationwide stroke registry and analysed. Patients were categorized and compared according to admission severity NIHSS 0-1 versus NIHSS 2-5 and intravenous thrombolysis use. RESULTS: Seven hundred and three (2%) of 35,113 patients presenting with NIHSS 0-1 and 6316 (13.9%) of 45,521 of patients presenting with NIHSS 2-5 underwent intravenous thrombolysis. In the NIHSS 0-1 group, intravenous thrombolysis was associated with early neurological deterioration (adjusted OR 8.84, CI 6.61-11.83), sICH (adjusted OR 9.32, CI 4.53-19.15) and lower rate of excellent outcome (mRS 0-1) at three months (adjusted OR 0.67, CI 0.5-0.9). In stroke patients with NIHSS 2-5, intravenous thrombolysis was associated with early neurological deterioration (adjusted OR 1.7, 1.47-1.98), sICH (adjusted OR 5.75, CI 4.45-7.45), and higher rate of excellent outcome (mRS 0-1) at three months (adjusted OR 1.21, CI 1.08-1.34). CONCLUSIONS: Among patients with NIHSS 0-1, intravenous thrombolysis did not increase the likelihood of excellent outcome. Moreover, potential signals of harm were observed. Further research seems to be warranted.

Acute Ischemic Stroke With Mild Symptoms-To Thrombolyse or Not to Thrombolyse?

Management of stroke with minor symptoms may represent a therapeutical dilemma as the hemorrhage risk of acute thrombolytic therapy may eventually outweigh the stroke severity. However, around 30% of patients presenting with minor stroke symptoms are ultimately left with disability. The objective of this review is to evaluate the current literature and evidence regarding the management of minor stroke, with a particular emphasis on the role of IV thrombolysis. Definition of minor stroke, pre-hospital recognition of minor stroke and stroke of unknown onset are discussed together with neuroimaging aspects and existing evidence for IV thrombolysis in minor strokes. Though current guidelines advise against the use of thrombolysis in those without clearly disabling symptoms due to a paucity of evidence, advanced imaging techniques may be able to identify those likely to benefit. Further research on this topic is ongoing.

European Stroke Organisation expedited recommendation for the use of short-term dual antiplatelet therapy early after minor stroke and high-risk TIA.

Prevention of early recurrent ischaemic stroke remains a priority in people with TIA or ischaemic stroke. A number of trials have recently been completed assessing the efficacy of short-term dual antiplatelet therapy (DAPT) versus single antiplatelet therapy early after minor or moderate stroke or high-risk TIA. We present an Expedited Recommendation for use of dual antiplatelet therapy early after ischaemic stroke and TIA on behalf of the ESO Guideline Board. We make a strong recommendation based on high quality of evidence for use of 21-days of dual antiplatelet therapy with aspirin and clopidogrel in people with a non-cardioembolic minor ischaemic stroke or high-risk TIA in the past 24 hours. We make a weak recommendation based on moderate quality evidence for 30-days of dual antiplatelet therapy with aspirin and ticagrelor in people with non-cardioembolic mild to moderate ischaemic stroke or high-risk TIA in the past 24 hours.

European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack.

The aim of the present European Stroke Organisation Transient Ischaemic Attack (TIA) management guideline document is to provide clinically useful evidence-based recommendations on approaches to triage, investigation and secondary prevention, particularly in the acute phase following TIA. The guidelines were prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined TIA clinically and pragmatically for generalisability as transient neurological symptoms, likely to be due to focal cerebral or ocular ischaemia, which last less than 24 hours. High risk TIA was defined based on clinical features in patients seen early after their event or having other features suggesting a high early risk of stroke (e.g. ABCD2 score of 4 or greater, or weakness or speech disturbance for greater than five minutes, or recurrent events, or significant ipsilateral large artery disease e.g. carotid stenosis, intracranial stenosis). Overall, we strongly recommend using dual antiplatelet treatment with clopidogrel and aspirin short term, in high-risk non-cardioembolic TIA patients, with an ABCD2 score of 4 or greater, as defined in randomised controlled trials (RCTs). We further recommend specialist review within 24 hours after the onset of TIA symptoms. We suggest review in a specialist TIA clinic rather than conventional outpatients, if managed in an outpatient setting. We make a recommendation to use either MRA or CTA in TIA patients for additional confirmation of large artery stenosis of 50% or greater, in order to guide further management, such as clarifying degree of carotid stenosis detected with carotid duplex ultrasound. We make a recommendation against using prediction tools (eg ABCD2 score) alone to identify high risk patients or to make triage and treatment decisions in suspected TIA patients as due to limited sensitivity of the scores, those with score value of 3 or less may include significant numbers of individual patients at risk of recurrent stroke, who require early assessment and treatment. These recommendations aim to emphasise the importance of prompt acute assessment and relevant secondary prevention. There are no data from randomised controlled trials on prediction tool use and optimal imaging strategies in suspected TIA.

European Stroke Organisation expedited recommendation for the use of short-term dual antiplatelet therapy early after minor stroke and high-risk TIA.

Prevention of early recurrent ischaemic stroke remains a priority in people with TIA or ischaemic stroke. A number of trials have recently been completed assessing the efficacy of short-term dual antiplatelet therapy (DAPT) versus single antiplatelet therapy early after minor or moderate stroke or high-risk TIA. We present an Expedited Recommendation for use of dual antiplatelet therapy early after ischaemic stroke and TIA on behalf of the ESO Guideline Board. We make a strong recommendation based on high quality of evidence for use of 21-days of dual antiplatelet therapy with aspirin and clopidogrel in people with a non-cardioembolic minor ischaemic stroke or high-risk TIA in the past 24 hours. We make a weak recommendation based on moderate quality evidence for 30-days of dual antiplatelet therapy with aspirin and ticagrelor in people with non-cardioembolic mild to moderate ischaemic stroke or high-risk TIA in the past 24 hours.

European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack.

The aim of the present European Stroke Organisation Transient Ischaemic Attack (TIA) management guideline document is to provide clinically useful evidence-based recommendations on approaches to triage, investigation and secondary prevention, particularly in the acute phase following TIA. The guidelines were prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined TIA clinically and pragmatically for generalisability as transient neurological symptoms, likely to be due to focal cerebral or ocular ischaemia, which last less than 24 hours. High risk TIA was defined based on clinical features in patients seen early after their event or having other features suggesting a high early risk of stroke (e.g. ABCD2 score of 4 or greater, or weakness or speech disturbance for greater than five minutes, or recurrent events, or significant ipsilateral large artery disease e.g. carotid stenosis, intracranial stenosis). Overall, we strongly recommend using dual antiplatelet treatment with clopidogrel and aspirin short term, in high-risk non-cardioembolic TIA patients, with an ABCD2 score of 4 or greater, as defined in randomised controlled trials (RCTs). We further recommend specialist review within 24 hours after the onset of TIA symptoms. We suggest review in a specialist TIA clinic rather than conventional outpatients, if managed in an outpatient setting. We make a recommendation to use either MRA or CTA in TIA patients for additional confirmation of large artery stenosis of 50% or greater, in order to guide further management, such as clarifying degree of carotid stenosis detected with carotid duplex ultrasound. We make a recommendation against using prediction tools (eg ABCD2 score) alone to identify high risk patients or to make triage and treatment decisions in suspected TIA patients as due to limited sensitivity of the scores, those with score value of 3 or less may include significant numbers of individual patients at risk of recurrent stroke, who require early assessment and treatment. These recommendations aim to emphasise the importance of prompt acute assessment and relevant secondary prevention. There are no data from randomised controlled trials on prediction tool use and optimal imaging strategies in suspected TIA.

Genetic identity and genotype × genotype interactions between symbionts outweigh species level effects in an insect microbiome.

Microbial symbionts often alter the phenotype of their host. Benefits and costs to hosts depend on many factors, including host genotype, symbiont species and genotype, and environmental conditions. Here, we present a study demonstrating genotype-by-genotype (G×G) interactions between multiple species of endosymbionts harboured by an insect, and the first to quantify the relative importance of G×G interactions compared with species interactions in such systems. In the most extensive study to date, we microinjected all possible combinations of five Hamiltonella defensa and five Fukatsuia symbiotica (X-type; PAXS) isolates into the pea aphid, Acyrthosiphon pisum. We applied several ecological challenges: a parasitoid wasp, a fungal pathogen, heat shock, and performance on different host plants. Surprisingly, genetic identity and genotype × genotype interactions explained far more of the phenotypic variation (on average 22% and 31% respectively) than species identity or species interactions (on average 12% and 0.4%, respectively). We determined the costs and benefits associated with co-infection, and how these compared to corresponding single infections. All phenotypes were highly reliant on individual isolates or interactions between isolates of the co-infecting partners. Our findings highlight the importance of exploring the eco-evolutionary consequences of these highly specific interactions in communities of co-inherited species.

STROKE-CARD care to prevent cardiovascular events and improve quality of life after acute ischaemic stroke or TIA: A randomised clinical trial.

BACKGROUND: Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke and other cardiovascular diseases and commonly suffer from reduced quality of life. We aimed to determine whether the disease management programme STROKE-CARD can prevent cardiovascular diseases and improve quality of life in these patients. METHODS: In this pragmatic open-label two-centre randomised controlled trial with blinded outcome assessment, we randomly assigned patients with acute ischaemic stroke or TIA (ABCD2 score ≥3) in a 2:1 ratio to receive STROKE-CARD care or standard care. STROKE-CARD care is a disease management programme by a multidisciplinary stroke team that comprises a standardised 3-month visit and access to a web-based patient portal targeting risk factor management, post-stroke complications, comorbidities and cardiovascular warning signs, rehabilitation demands, and patient education, counselling, and self-empowerment. Co-primary outcomes were analysed on an intention-to-treat basis and were: (i) major cardiovascular disease events defined as nonfatal ischaemic or haemorrhagic stroke, nonfatal myocardial infarction, or vascular death occurring between hospital discharge and 12 months; and (ii) health-related quality of life at 12 months quantified with the EuroQol-5-Dimensions-3-Levels (EQ-5D-3L) overall utility score. This trial is registered with ClinicalTrials.gov, number NCT02156778. FINDINGS: Of 2149 patients enrolled between January 2014 and December 2017 (mean age 69 years, 41% female, 83% with ischaemic stroke, 17% with TIA), 1438 were assigned to STROKE-CARD care and 711 to standard care. Major cardiovascular disease events occurred in 78 patients in the STROKE-CARD care group (5.4%) and in 59 patients in the standard care group (8.3%) (hazard ratio, 0.63; 95% confidence interval: 0.45-0.88; P=0.007). STROKE-CARD care also led to a better EQ-5D-3L overall utility score at 12 months (P<0.001). Among pre-specified secondary outcomes, STROKE-CARD care improved all individual EQ-5D-3L dimensions and functional outcome on the modified Rankin Scale at 12 months. Post hoc explanatory analyses identified considerable demands for additional rehabilitation and refinement of preventive therapy regimes at the 3-month visit and high proportions of post-stroke complications and warning signs of imminent cardiovascular diseases within the first three months. INTERPRETATION: The pragmatic and easily implementable STROKE-CARD care programme reduced cardiovascular risk and improved health-related quality of life and functional outcome in patients with acute ischaemic stroke or TIA. FUNDING: Tirol Kliniken, Tyrolean Health Insurance Company, Tyrol Health Care Funds, Boehringer Ingelheim, Nstim Services, Sanofi, Bayer Healthcare.

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Trends of r-tPA (Recombinant Tissue-Type Plasminogen Activator) Treatment and Treatment-Influencing Factors in Acute Ischemic Stroke.

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.

Thrombolysis in Stroke With Unknown Onset Based on Non-Contrast Computerized Tomography (TRUST CT).

Background Intravenous thrombolysis (IVT) in wake-up stroke (WUS) or stroke with unknown onset (SUO) has been recently proven to be safe and effective using advanced neuroimaging (magnetic resonance imaging or computerized tomography-perfusion) for patient selection. However, in most of the thrombolyzing centers advanced neuroimaging is not instantly available. We hypothesize that pragmatic non-contrast computed tomography-based IVT in WUS/SUO may be feasible and safe. Methods and Results TRUST-CT (Thrombolysis in Stroke With Unknown Onset Based on Non-Contrast Computerized Tomography) is an international multicenter registry-based study. WUS/SUO patients undergoing non-contrast computed tomography-based IVT with National Institute of Health Stroke Scale ≥4 and initial Alberta Stroke Program Early Computerized Tomography score ≥7 were included and compared with propensity score matched non-thrombolyzed WUS/SUO controls. Primary end point was the incidence of symptomatic intracranial hemorrhage; secondary end points included 24-hour National Institute of Health Stroke Scale improvement of ≥4 and modified Rankin Scale at 90 days. One hundred and seventeen WUS/SUO patients treated with non-contrast computed tomography-based IVT were included. As compared with 112 controls, the median admission National Institute of Health Stroke Scale was 10 and the median Alberta Stroke Program Early Computerized Tomography score was 10 in both groups. Four (3.4%) IVT patients and one control patient (0.9%) suffered symptomatic intracranial hemorrhage (adjusted odds ratio 7.9, 95% CI 0.65-96, P=0.1). A decrease of ≥4 National Institute of Health Stroke Scale points was observed in 67 (57.3%) of IVT patients as compared with 25 (22.3%) in controls (adjusted odds ratio 5.8, CI 3.0-11.2, P<0.001). A months, 39 (33.3%) IVT patients reached a modified Rankin Scale score of 0 or 1 versus 23 (20.5%) controls (adjusted odds ratio 1.94, CI 1.0-3.76, P=0.05). Conclusions Non-contrast computed tomography-based thrombolysis in WUS/SUO seems feasible and safe and may be effective. Randomized prospective comparisons are warranted. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT03634748.