Intravenous Recombinant Tissue Plasminogen Activator Research Articles

Patterns of Acute Ischemic Stroke Treatment from 2010 to 2020: An Evolving Landscape in Stroke Management Following Thrombectomy Trials.

Population-based studies on stroke can help guide the care of patients with acute ischemic stroke (AIS) by providing health care communities with information regarding the current usage of stroke treatments. It remains unclear how rapidly new techniques, particularly endovascular stroke treatment (EST), are being adopted and whether there is any disparity in their availability. Although studies using the National Inpatient Sample (NIS) have been conducted, updated studies over a longer period may provide further insights. This study aimed to understand patterns of AIS treatment, discharge disposition, in-hospital mortality, and mean length of stay (LOS) for each modality from 2010 to 2020 using the NIS database. This retrospective longitudinal study was conducted using NIS data from 2010 to 2020. Patients were categorized into groups based on whether they received intravenous recombinant tissue plasminogen activator (rt-PA), EST, both rt-PA and EST (combined therapy), or supportive care alone. Demographic, socioeconomic, regional, insurance, and hospital data were also obtained. The primary outcome was the proportion of patients receiving each modality, whereas the secondary outcomes were in-hospital mortality, mean LOS, and discharge disposition. The usage rates increased (p < 0.001) in all groups between 2010 and 2020 (rt-PA: 5.09% to 8.39%, EST: 0.31% to 4.40%, and rt-PA+EST: 0.46% to 1.09%). The highest increase in usage was observed for EST, with a thirteen-fold increase. Mortality decreased from 2010 to 2020 in all groups (rt-PA: 8.45% to 3.54%, EST: 25.22% to 12.50%, and rt-PA+EST: 21.12% in 2010 to 9.30%) (p < 0.001). Combination therapy demonstrated the greatest improvement, with an 11.2% reduction in absolute mortality. Mean LOS was reduced for patients who received rt-PA (6.8 to 4.8 days), EST (9.3 to 8.9 days), and combined therapy (10.0 to 8.3 days) (p < 0.001) over the study period. The proportion of patients discharged to home increased for rt-PA (29.01% to 41.85%), EST (14.13% to 17.70%), and combined therapy (12.89% to 24.29%) (p < 0.001). Overall, stroke treatment usage was higher among the higher income groups, regardless of race. Higher usage was also observed for Whites in the West and Hispanic ethnicities in the South and West. Regardless of income or treatment method, utilization rates were lower for Black patients. Utilization rates were lower for Black patients with Medicare, Medicaid, or self-pay than for White patients. Our study demonstrated that endovascular stroke treatment continues to expand, leading to better outcomes for mortality, LOS, and home discharge. Despite these positive patterns, there are visible inequities across regions, income status, and races.

Left ventricular systolic dysfunction predicts clinical prognosis in patients with acute ischemic stroke after intravenous thrombolysis.

Although intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis is the most effective early treatment for acute ischemic stroke (AIS), outcomes vary greatly among patients. Left ventricular systolic dysfunction (LVSD) is prone to distant organ ischemia and may be a predictor for poor prognosis in AIS patients undergoing intravenous thrombolysis (IVT). Our aim was to investigate the predictivity of LVSD diagnosis (as measured by left ventricular ejection fraction (LVEF)) on 90-day clinical outcomes in AIS patients undergoing thrombolysis. The current prospective cohort study continuously enrolled 273 AIS patients from the National Stroke Prevention and Treatment Engineering Management Special Database who underwent IVT and completed echocardiography within 24 h of admission between 2021 and 2023. LVSD was examined by evaluation of the echocardiographic LVEF values using Simpson's biplane method of discs in line with international guidelines, and defined as a LVEF value < 50%. Multivariable ordinal logistic regression model was performed to analyze the association between LVEF and functional outcome at 3 months. Restricted cubic spline (RCS) was used to examine the shape of the dose-response association between reduced LVEF and poor functional outcomes. Subgroup analysis was also employed to further verify the reliability and practicability of the results. Baseline data analysis showed LVSD patients had more comorbidities including on multivariate analyses, LVSD (OR 2.78, 95% CI 1.23 to 6.24, P=0.014), pre-existing diabetes mellitus (OR 2.08, 95% CI 1.11 to 3.90, P=0.023) and NIHSS on arrival (OR 1.31, 95% CI 1.21 to 1.49, P<0.001) were independent predictors of poor functional outcomes (mRS ≥ 3) at 3 months. Multivariable-adjusted spline regression indicated a linear dose-response association between LVEF after IVT and poor functional outcomes (p for linearity < 0.001), with the optimal cutoff values of LVEF being 0.48. Our finding indicated that AIS patients with LVSD after IVT had poorer outcomes, suggesting the need to monitor and optimize LVEF in stroke management.

Language assessment in persons with aphasia early after thrombolysis: the utility of multilevel procedures of discourse analysis

ABSTRACT Background Clinical guidelines recommend the administration of intravenous recombinant tissue plasminogen activator thrombolytic treatment to persons who suffered ischemic stroke within 4,5 hours since onset. However, the available evidence on the potential improvement of language after thrombolysis is still scanty. Aims This study assessed the effect of thrombolytic treatment in language recovery in persons with stroke aphasia (PWA) comparing the efficacy of traditional language assessments and a multilevel procedure of discourse analysis applied to the Cookie Theft picture descriptions taken from the National Institute of Health Stroke Scale (NIHSS). Methods and procedures Fortyeight individuals participated in the study: sixteen PWA who received thrombolysis; sixteen PWA who did not receive it; sixteen healthy controls. The two groups of PWA were balanced in terms of age, education, gender, lateralization of the lesion, and stroke severity. They were administered the NIHSS and a bedside language assessment battery when entering the neurological clinic (T0) and after approximately 72 hours (T1). Their narrative discourse descriptions were analyzed with a multilevel procedure for discourse analysis. Outcomes and results The two groups of PWA had similar linguistic difficulties at T0 as reflected by comparable Composite Verbal Scores and performance on traditional linguistic bedside assessment (Aphasia PostStroke Acute Assessment test; Furlanis et al., 2018). Discourse analysis highlighted the presence of more omissions of function words and errors of cohesion in the PWA who would receive thrombolysis with respect to healthy controls and allowed for the identification, in both groups, of difficulties that could not be detected through a traditional assessment. At T1 the analyses showed the presence of improvements likely reflecting a generalized spontaneous recovery in both groups of PWA and a more specific recovery triggered by thrombolysis concerning the production of global coherence errors in treated patients only. An inspection of the gravity of the linguistic symptoms at the individual level revealed high interindividual variability in this early phase suggesting that thrombolysis reduced the severity of the impairment also in the production of informative words. Conclusions Thrombolysis reduces the gravity of some linguistic symptoms within a few hours after treatment. Multilevel procedures of discourse analysis can identify these subtle improvements.

Factors predicting functional outcome after rtPA for patients with acute ischemic stroke

BackgroundAccurate outcome prediction for patients with acute ischemic stroke after intravenous recombinant tissue plasminogen activator (rtPA) treatment is essential for optimizing patients’ management. We aimed to identify factors associated with unfavorable outcomes following intravenous rtPA treatment. This study was carried out on 162 patients who presented with acute ischemic stroke within 4.5 h from onset of neurological symptoms and were eligible for intravenous rtPA. After exclusion of 48 patients, 114 patients were finally eligible for follow-up. After complete medical and neurological history, complete medical and neurological examination and brain image (CT and or MRI brain) were collected from the patients. patients eligible were included in the study. NIHS scale was assessed for all patients at time of admission, after 24 h, and follow-up for 3 months.ResultsAfter a 90-day follow-up period for 114 patients with acute ischemic stroke after rtPA, 35.8% had good outcome (MRS; 0–2), 18.5% had partial outcome (MRS; 3–4) and 12.5% had poor outcome (MRS; 5–6). Atrial fibrillation (AF), PH of stroke, stroke severity, and severity of symptom (NIHSS) score were significantly (P: 0.004, 0.001, 0.007 and 0.001) correlated with poor outcome after rtPA. Similarly, old age, high blood pressure at time of presentation, hypertension, and dyslipidemia were showed to carry poor outcome.ConclusionsAF, high NIHSS score, PH of stroke, previous stroke, hypertension, dyslipidemia, and high blood pressure on presentation were significantly correlated with poor functional outcome.

Readmission Rates Among Acute Reperfusion Treatment Modalities for Patients With Ischemic Stroke

Background and purpose Understanding various aspects associated with readmission after acute ischemic stroke (AIS) is an important priority. Our study aims to examine whether 60-day readmission rates differed among patients with AIS who were treated with different acute reperfusion treatment modalities along with associated clinical factors. Methods This is a retrospective analysis of a continuous cohort of patient with AIS, who received either intravenous recombinant tissue plasminogen activator (IV rtPA), endovascular treatment (EVT) or both, and were discharged alive. Patients readmitted within 60 days were identified as the readmission group. Multivariable logistic regression was used to identify all-cause readmission post-stroke between treatment groups. Results The final cohort comprised of 358 patients with AIS receiving IV rtPA only (N = 160), EVT only (N = 106), or both (N = 92). Fifty-six patients were readmitted to the hospital within 60-day follow-up period. The adjusted logistic regression model indicated that compared to patients who received IV tPA only, patients receiving both IV rtPA and EVT had significantly lower odds (OR = .27; 95% CI = .10, .75)) of getting readmitted within 60-day post-discharge from stroke admission. Conclusion In this sample of AIS hospitalizations, treatment-type was positively associated with 60-day readmission. Future studies are necessary to understand whether treatment-related adverse events, and readmission are avoidable.

Safety and efficacy of N-acetylcysteine (NAC) as an adjunct to standard treatment in patients with acute ischemic stroke: a randomized controlled pilot trial (NACTLYS)

There is a pressing clinical need for thrombolytic agents that can effectively disaggregate arterial thrombi in acute ischemic stroke without significantly increasing the risk of bleeding. This pilot study aimed to investigate the safety and efficacy of N-acetylcysteine (NAC) as an adjunctive therapy to intravenous recombinant tissue plasminogen activator (rtPA or alteplase). A randomized, open-label, blinded assessor pilot study was conducted. Patients presenting with an acute ischemic stroke within 4.5 h from onset were randomized into two groups: intravenous NAC and rtPA or rtPA alone. Primary outcomes included intracerebral hemorrhage, symptomatic intracerebral hemorrhage, extracranial bleeding, and adverse reactions. Secondary outcomes comprised major neurological improvement assessed by (National Institute of Health Stroke Scale) NIHSS at 24 h, recanalization on first run of angiography in patients who underwent thrombectomy or on repeat vascular imaging at 24 h, modified Rankin scale, and three-month mortality. Forty patients were enrolled, with 21 receiving only rtPA and 19 receiving NAC with rtPA. Baseline characteristics were comparable among groups. No significant differences were observed in adverse events (p = 0.99), intracranial hemorrhage (p = 0.21), symptomatic intracerebral hemorrhage (p = 0.47), or extracranial bleeding (p = 0.21). Median NIHSS at 24 h was significantly lower in the intervention group (p = 0.03). Functional outcomes and three-month mortality were similar between groups (p = 0.85 and p = 0.99 respectively). The co-administration of N-acetylcysteine with alteplase did not significantly alter safety profiles, morbidity, or mortality at 3 months. While no substantial differences were noted, a slightly improved early neurological outcome was observed in the intervention arm. The study's findings were constrained by a small sample size, emphasizing the necessity for future large-scale trials to comprehensively evaluate the safety and efficacy of N-acetylcysteine as a thrombolytic agent in acute ischemic stroke.Trial Registration Clinical Trials Registry India—CTRI/2019/05/019305.

Factors affecting improvement after intravenous administration of recombinant tissue plasminogen activator (rtPA) among patients with acute ischemic stroke: A historical cohort study.

One of the most effective treatments for patients with acute ischemic stroke (AIS) is intravenous recombinant tissue plasminogen activator (rtPA) which can minimize mortality and morbidities. In this historical cohort study, we investigate the factors affecting clinical outcomes after IV thrombolysis for AIS. We included 87 patients with acute ischemic stroke who were treated with rtPA between 2015 and 2019. Demographic and clinical data were recorded. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the clinical outcomes. 36 patients showed lack of improvement at discharge. In unadjusted model, hypercholesterolemia was the only predictor of lack of improvement (P= 0.043; OR=0.304; CI= 0.096-0.963). After adjusting, hypertension (P= 0.018; OR= 0.18; CI= 0.043-0.749) and hypercholesterolemia (P= 0.008; OR= 8.68; CI= 1.773-42.54) were independent determinants of lack of clinical response. To evaluate risk factors in association with the duration of hospitalization, we found variables which lengthened hospitalization span including; age over 60 years (HR= 0.42 P= 0.002), hypercholesterolemia (HR= 2.19 P= 0.031), Angiotensin-converting enzyme (ACE) Inhibitors consumption (HR= 1.87 P= 0.022), and type of infarction (non-lacunar) (HR= 0.51 P= 0.026). Results indicated no considerable relationship between dose of rtPA and the appropriate response to treatment (OR=8.686 P= 0.324). The closer dose of rtPA goes up to standard range, the more chance of improvement will gain without increasing the risk of symptomatic intra-cerebral hemorrhage (SICH). Determining factors involved in intravenous reperfusion outcomes help physicians to identify the patients who benefit the most from rtPA.

Impact of Successful Recanalization and Clinical Outcomes of Patients With Acute Ischemic Stroke with 5 or More Thrombectomy Passes

Background As the number of thrombectomy passes increases during endovascular therapy (EVT) for acute stroke, neurointerventionalists must weigh the risks of potential complications against the risk of failing to recanalize the affected vessel. Thus, we investigated the effectiveness and safety of EVT for patients with acute stroke in which ≥5 EVT passes were performed. Methods This retrospective cohort study from January 2013 to December 2022 included 31 thrombectomy‐capable centers. Patients in whom ≥5 EVT passes were made were included in the analysis. The patients with successful recanalization defined as modified Thrombolysis in Cerebral Infarction ≥2b at 5, 6, 7, or more passes were compared with unsuccessful recanalization. We also compared procedure time, separated by 30 minutes. Primary outcome was a favorable 90‐day outcome (modified Rankin scale score of 0–2). Secondary outcomes were intracranial hemorrhage and death. Results A total of 407 patients met the inclusion criteria, of which 175 were women (43.1%); the mean age was 67.3 years. In 265 (65.1%) patients, successful recanalization was achieved: 134 patients with 5 passes, 67 patients with 6 passes, and 64 with ≥7 passes. Intravenous recombinant tissue plasminogen activator administration was more common in the unsuccessful recanalization group (successful recanalization with 5, 6, and ≥7 EVT passes and unsuccessful recanalization: 35.3%, 30.3%, 18.8%, and 45.4%, respectively). Successful recanalization with 5, 6, and ≥7 EVT passes was associated with favorable outcome compared with unsuccessful recanalization group (adjusted odds ratio successful recanalization with 5, 6, and ≥7 EVT passes to unsuccessful recanalization [95% CIs]: 8.29 [2.13–32.3]; 14.0 [3.27–60.3]; and 5.26 [1.12–24.8], respectively). However, symptomatic intracranial hemorrhage was not significantly different between the groups. Regarding procedure time, favorable outcome was not significantly different in each group, while symptomatic intracranial hemorrhage occurred more frequently in the 60 to 89 minutes group compared with the &lt;30 minutes group (adjusted odds ratio, 60–89 minutes group to &lt;30 minutes group [95% CI]: 5.86 [1.09–31.6]). Conclusion These findings suggest that a benefit in outcome persists for recanalization, without significant increase in complications. In addition, there was no significant difference in favorable outcomes among procedure time.

Comparison between healthcare quality in primary stroke centers and comprehensive stroke centers for acute stroke patients: evidence from the Chinese Stroke Center Alliance

To improve stroke care quality, the guidelines for stroke center construction in China recommended establishing primary stroke centers (PSCs) and comprehensive stroke centers (CSCs). We aimed to compare stroke care quality between the two types of centers. Data were collected from acute stroke patients admitted to PSCs or CSCs in the China Stroke Center Alliance program. Twenty-one individual guideline-recommended performance measures and two summary measures were compared between the two groups. Multivariable logistic regression models were used to examine the association between stroke center status (CSC vs. PSC) and healthcare quality. Data from 750,594 stroke patients from 1474 stroke centers (252 CSCs and 1222PSCs) were analyzed. For many components of healthcare performance in stroke patients, comparable levels of performance were observed between CSCs and PCSs. Nonetheless, CSCs outperformed PSCs in the areas of administering intravenous recombinant tissue plasminogen activator within 4.5h (aOR=1.31 [95% CI: 1.07-1.60]), rehabilitation for acute ischaemic stroke (AIS) (aOR=1.19 [95% CI: 1.01-1.40]), and the provision of hypoglycemic medication and statin therapy upon discharge for AIS (aOR=1.26 [95% CI: 1.00-1.59] and aOR=1.28 [95% CI: 1.04-1.59], respectively). More patients with intracerebral haemorrhage and subarachnoid haemorrhage received neurosurgery in CSCs (14.4% vs. 10.6% and 51.0% vs. 33.9%, respectively). Additionally, CSCs had higher in-hospital mortality than PSCs (aOR=1.33 [95% CI: 1.01-1.73]). Overall PSCs provided equivalent care for many quality measures to CSCs in China with the exception of thrombolysis, rehabilitation access, and medication at discharge for AIS, whereby improvements should be directed. Nevertheless, PSCs have demonstrated lower risk-adjusted in-hospital mortality rates. The National Key Research and Development Projects of China.

Baseline vitamin D levels and functional outcome in thrombolyzed stroke patients

BackgroundThe primary treatment for acute ischemic stroke (AIS) patients is intravenous recombinant tissue plasminogen activator (IV rt-PA). A link between vitamin D insufficiency and worse post-stroke outcomes and more severe strokes was suggested. The present study aimed to assess the prognostic significance of baseline vitamin D levels in AIS patients treated with rt-PA. The present prospective study was conducted 66 patients with acute ischemic stroke within the therapeutic window and treated with rt-PA. Vitamin D levels were assessed using commercial double antibody sandwich enzyme linked immunosorbent assay. The primary study outcome is patient disability of any degree as assessed by the modified Rankin scale (mRS).ResultsThe present study included 66 ischemic stroke patients treated with rt-PA. At baseline, there were 37 patients (56.1%) with low vitamin D levels. Comparison between patients with normal and low vitamin D levels regarding baseline data revealed that the former group were significantly younger and had significantly smaller infarct size patients with normal vitamin D had significantly lower NIHSS at day 2 and day 7. Interestingly, patients with low vitamin D levels had significantly higher frequency of rt-PA related hemorrhage, higher frequency of chest infection, longer hospital stay and higher mRS at 90 days. Multivariate logistic regression analysis identified vitamin D level as significant predictor of functional outcome at 90 days.ConclusionsBaseline vitamin D levels is considered a significant predictor of functional outcome in AIS patients treated with rt-PA. It’s also related to infarct size and treatment complications.

Impact of areal socioeconomic status on prehospital delay of acute ischaemic stroke: retrospective cohort study from a prefecture-wide survey in Japan

ObjectivesTo examine whether the Areal Deprivation Index (ADI), an indicator of the socioeconomic status of the community the patient resides in, is associated with delayed arrival at the hospital and...

Low-dose intravenous recombinant tissue plasminogen activator in acute ischemic stroke without large vessel occlusion screened by 3T MRI.

Globally, there are more than six million deaths due to cerebrovascular disease, which is the second leading cause of death. Although the imaging findings of magnetic resonance imaging (MRI) are more accurate than computed tomography for acute ischemic stroke (AIS), it is uncommon in recombinant tissue plasminogen activator (rTPA) treatment. Alteplase is not only strongly recommended treatment for acute ischemic stroke within 4.5 hours, but also decreases the disability and mortality rate. Besides, low-dose rTPA was associated with significant reductions in symptomatic intracerebral hemorrhage (sICH), compared with standard one. However, the benefits of low-dose rTPA for the treatment of AIS without large vessel occlusion (LVO) have not been fully demonstrated. We evaluated whether the low-dose rTPA in AIS without LVO could improve prognosis in patients three months post-treatment. This was a cross-sectional study on patients with AIS treated within 4.5 hours of symptom onset admitted to Can Tho S.I.S General Hospital between February 2019 and July 2021. The eligibility criteria were patients aged > 18 years treated with low-dose rTPA (0.6 mg/kg) and screened by 3T MRI. Patients with a pre-hospital modified Rankin score (mRS) ≥ 2 points, intracranial hemorrhage, LVO, or ≥ 3 microbleeds on brain MRI were excluded. The primary outcomes were the favorable outcome rate at three months and safety, which were evaluated by the rates of intracranial hemorrhage and mortality at three months. This study enrolled 92 eligible patients between February 2019 and July 2021. Their National Institute of Health Stroke Scale (NIHSS) scores were 7.5 ± 3.7 at admission, 3.3 ± 3.5 at discharge or seven days after discharge, and 2.2 ± 2.8 at three months. Their mRS were 2.9 ± 0.8 at admission, 1.4 ± 1.3 at discharge or seven days after discharge, and 1.1 ± 1.1 at three months. Elevated cardiac enzymes, age ≥ 75 years, and body mass index ≥ 25 were associated with increased poor outcomes at three months. While AIS was more common in men than women, a similar number of men (33.3%) and women had poor mRS. Three patients had complications associated with low-dose rTPA treatment: one (1.1%) had intracranial hemorrhage, one (1.1%) had new infarcts, and one (1.1%) had gastrointestinal bleeding. No deaths occurred within three months. Our study indicates the efficacy and safety of low-dose rTPA treatment for AIS without LVO within 4.5 hours. Patient selection for rTPA by 3T MRI decreased complications and mortality.

Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke

DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown. To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment. This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022. Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio. The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity. Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group. Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo. ClinicalTrials.gov Identifier: NCT03539445.

Effectiveness of a Quality Improvement Intervention on Reperfusion Treatment for Patients With Acute Ischemic Stroke

Reperfusion therapy is the most effective treatment for acute ischemic stroke but remains underused in China. To evaluate the effect of a problem-oriented, culturally adapted, targeted quality improvement intervention on reperfusion therapy for patients with acute ischemic stroke in China. In this stepped-wedge cluster randomized clinical trial, patients from 16 secondary and 33 tertiary hospitals in China with acute ischemic stroke within 6 hours of symptom onset were consecutively recruited between July 1, 2018, and June 30, 2020. Hospitals were randomly assigned to 1 of 3 sequences to receive the targeted quality improvement intervention (n = 5689), in which workflow reconstruction was promoted to reduce in-hospital reperfusion treatment delays, or usual care (n = 6443), in which conventional stroke care was left to the discretion of the stroke team. The primary outcome was the reperfusion therapy rate, a composite outcome of intravenous recombinant tissue plasminogen activator (IV rtPA) or endovascular thrombectomy (EVT) for eligible patients who arrived within 3.5 or 4.5 hours of symptom onset. Secondary outcomes were the IV rtPA administration rate among eligible patients who arrived within 3.5 hours of symptom onset, the EVT rate among eligible participants who arrived within 4.5 hours of symptom onset, the proportion of patients with door-to-needle time within 60 minutes, the proportion of patients with door-to-puncture time within 90 minutes, in-hospital mortality, and 3-month disability as measured by a modified Rankin Scale score greater than 2. All 12 132 eligible patients (mean [SD] age, 66 [12.1] years; 7759 male [64.0%]) completed the trial. The reperfusion rate was 53.5% (3046 of 5689) for the eligible patients in the intervention period and 43.9% (2830 of 6443) in the control period. No significant improvement in primary outcomes was found for the intervention after adjusting for cluster, period, and imbalanced baseline covariates (adjusted risk difference [ARD], 5.5%; 95% CI, -8.0% to 19.0%; adjusted odds ratio [AOR], 1.26; 95% CI, 0.72-2.21) or for the secondary outcomes. However, significant improvements were found in secondary hospitals for reperfusion therapy (1081 of 1870 patients [57.8%] vs 945 of 2022 patients [42.9%]; ARD, 19.0%; 95% CI, 6.4%-31.6%; AOR, 2.24; 95% CI, 1.29-3.88), IV rtPA administration (1062 of 1826 patients [58.2%] vs 916 of 2170 patients [42.2%]; ARD, 20.3%; 95% CI, 7.4%-33.1%; AOR, 2.37; 95% CI, 1.34-4.19), and EVT (51 of 231 patients [22.1%] vs 37 of 259 patients [14.3%]; ARD, 13.6%; 95% CI, 1.0%-26.3%; AOR, 3.03; 95% CI, 1.11-8.25) in subgroup analyses. In this stepped-wedge cluster randomized clinical trial of patients with acute ischemic stroke in China, the use of a targeted quality improvement intervention compared with usual care did not improve the reperfusion therapy rate. However, the intervention may be effective in secondary hospitals. ClinicalTrials.gov Identifier: NCT03578107.

Safety and Efficacy of Intravenous Thrombolysis in the 3- to 4.5-hour Window in Acute Ischemic Stroke Patients Who Have Both Diabetes Mellitus and History of Prior Stroke

Background: For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients.Methods: Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927).Results: The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; &lt;i&gt;p&lt;/i&gt;&gt;0.999) and 3-month mortality (10.7% vs. 10.2%; &lt;i&gt;p&lt;/i&gt;=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]).Conclusions: In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

Safety of recanalization therapy in patients with acute ischemic stroke on direct oral anticoagulants: A sub-analysis of PASTA registry study

BackgroundThe safety of intravenous recombinant tissue plasminogen activator (rtPA) and mechanical thrombectomy (MT) in patients treated with direct oral anticoagulants (DOACs) before stroke has not been fully investigated. Therefore, we aimed to investigate the safety of recanalization therapy in patients receiving DOACs. MethodsWe assessed data from a prospective multicenter registry of patients with stroke, including those with acute ischemic stroke (AIS) treated with rtPA and/or MT who were administered DOACs. We evaluated the safety of recanalization considering the DOACs dosage and interval between the last DOAC intake and recanalization. ResultsThe final analysis included 108 patients (women, n = 54; median age, 81 years; DOAC overdose, n = 7; appropriate dose, n = 74; and inappropriate low dose, n = 27). The rate of any ICH differed significantly among overdose-, appropriate dose-, and inappropriate-low dose DOACs groups (71.4, 23.0, and 33.3%, respectively; P = 0.0121), whereas no significant difference was observed in respect of symptomatic ICH (P = 0.6895). Multivariate analysis showed that the National Institutes of Health Stroke Scale score on admission (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.01–1.11; P = 0.0267) and overdose-DOAC (OR: 8.40, 95% CI: 1.24–56.88; P = 0.0291) were independently associated with any ICH. No relationship was observed between the timing of the last DOAC intake and occurrence of ICH in patients treated with rtPA and/or MT (all P > 0.05). ConclusionRecanalization therapy during DOAC treatment may be safe in selected patients with AIS, if it is performed >4 h after the last DOAC intake and the patient is not overdosed with DOACs. Registrationhttps://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958

Association of admission neutrophil serine proteinases levels with the outcomes of acute ischemic stroke: a prospective cohort study

BackgroundNeutrophil serine proteinases (NSPs), released by activated neutrophils, are key proteins involved in the pathophysiologic processes of stroke. NSPs are also implicated in the process and response of thrombolysis. This study aimed to analyze three NSPs (neutrophil elastase, cathepsin G, and proteinase 3) in relation to acute ischemic stroke (AIS) outcomes and in relation to the outcomes of patients treated with intravenous recombinant tissue plasminogen activator (IV-rtPA).MethodsAmong 736 patients prospectively recruited at the stroke center from 2018 to 2019, 342 patients diagnosed with confirmed AIS were included. Plasma neutrophil elastase (NE), cathepsin G (CTSG), and proteinase 3 (PR3) concentrations were measured on admission. The primary endpoint was unfavorable outcome defined as modified Rankin Scale score 3–6 at 3 months, and the secondary endpoints were symptomatic intracerebral hemorrhage (sICH) within 48 h, and mortality within 3 months. In the subgroup of patients who received IV-rtPA, post-thrombolysis early neurological improvement (ENI) (defined as National Institutes of Health Stroke Scale score = 0 or decrease of ≥ 4 within 24 h after thrombolysis) was also included as the secondary endpoint. Univariate and multivariate logistic regression analyses were performed to evaluate the association between NSPs levels and AIS outcomes.ResultsHigher NE and PR3 plasma levels were associated with the 3-month mortality and 3-month unfavorable outcome. Higher NE plasma levels were also associated with the risk of sICH after AIS. After adjusting for potential confounders, plasma NE level > 229.56 ng/mL (odds ratio [OR] = 4.478 [2.344–8.554]) and PR3 > 388.77 ng/mL (OR = 2.805 [1.504–5.231]) independently predicted the 3-month unfavorable outcome. Regarding rtPA treatment, patients with NE plasma concentration > 177.22 ng/mL (OR = 8.931 [2.330–34.238]) or PR3 > 388.77 ng/mL (OR = 4.275 [1.045–17.491]) were over 4 times more likely to suffer unfavorable outcomes after rtPA treatment. The addition of NE and PR3 to clinical predictors of unfavorable functional outcome after AIS and the outcome after rtPA treatment improved discrimination as well as reclassification (integrated discrimination improvement = 8.2% and 18.1%, continuous net reclassification improvement = 100.0% and 91.8%, respectively).ConclusionsPlasma NE and PR3 are novel and independent predictors of 3-month functional outcomes after AIS. Plasma NE and PR3 also possess predictive value to identify patients with unfavorable outcomes after rtPA treatment. NE is probably an important mediator of the effects of neutrophils on stroke outcomes, which worth further investigation.

Abstract Number ‐ 242: Safety and Effectiveness of Intravenous Thrombolytic in Patients with Concurrent Migraine‐Headaches and Focal Neurological Deficits.

Introduction It is relatively well recognized that migraine headaches can present with focal neurological deficits. Current guidelines do not exclude such patients from receiving intravenous recombinant tissue plasminogen activator (rt‐PA). Methods We reviewed the records of migraine patients with ischemic stroke using a combination of retrospective chart review and prospective identification. The migraine was classified based on the criteria proposed by the third International Classification of Headache Disorders (ICHD‐3) into migraine with aura, and hemiplegic migraine. We ascertained rates of early neurological improvement (defined by reduction in National Institutes of Health Stroke Scale (NIHSS) score of 4 points or greater or NIHSS score of 0 at24 hours), any intracerebral hemorrhage within 24 hours, and excellent functional outcome based on modified Rankin Scale (mRS 0–1) at one month. Results A total of 25 patients (mean age ± SD; 45.3 ± 10.6 years; 15 were women) who met the criteria of migraine headaches concurrently presented with focal neurological deficits and received intravenous rt‐PA. The migraine was classified as hemiplegic migraine and migraine with aura in 22 and 3 patients, respectively. Intravenous rt‐PA was administered at a mean period of 142 minutes(range 60–255 minutes). Computed tomographic angiography was performed in 24 patients and did not reveal any large vessel arterial occlusion. Early neurological improvement was seen in 13 of 25 patients. None of the patients developed post thrombolytic intracerebral hemorrhage. Excellent functional outcome was seen in all patients. Diffusion‐weighted magnetic resonance imaging (MRI) was performed in 25 patients within 72 hours of symptom onset and demonstrated a new infarction in 1 patient. Conclusions In our analysis, intravenous rt‐PA was associated with high rates of early neurological improvement and excellent functional outcome at 1 month in patients with concurrent migraine headaches and focal neurological deficits.

Specificity and sensitivity of the SeLECT score in predicting late seizures in patients undergoing intravenous thrombolytic treatment and the effect of diabetes mellitus and leukoaraiosis

Seizures after stroke can negatively affect the prognosis of ischemic stroke and cause a decrease in quality of life. The efficacy of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment in acute ischemic stroke has been demonstrated in many studies, and IV rt-PA treatment has been increasingly used around the world. The SeLECT score is a useful score for the prediction of late seizures after stroke and includes the severity of stroke (Se), large artery atherosclerosis (L), early seizure (E), cortical involvement (C), and the territory of the middle cerebral artery (T). However, the specificity and sensitivity of the SeLECT score have not been studied in acute ischemic stroke patients that received IV rt-PA treatment. In the present study, we aimed to validate and develop the SeLECT score in acute ischemic stroke patients receiving IV rt-PA treatment. The present study included 157 patients who received IV thrombolytic treatment in our third-stage hospital. The 1-year seizure rates of the patients were detected. SeLECT scores were calculated. In our study, we found that the SeLECT score had low sensitivity but high specificity for predicting the likelihood of late seizure after stroke in patients administered IV rt-PA therapy. In addition to the SeLECT score, we found that the specificity and sensitivity were higher when we evaluated diabetes mellitus (DM) and leukoaraiosis. We found that DM was an independent risk factor for late seizures after stroke in a patient group receiving thrombolytic therapy, and late seizures after stroke were less frequent in patients with leukoaraiosis.

Comparison of Effectiveness and Safety of Low-Dose Versus Standard-Dose Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke: A Meta-Analysis.

The aim of the present meta-analysis is to compare the efficacy and safety of low-dose and standard-doserecombinant tissue plasminogen activators (r-tPA) in patients with acute ischemic stroke. The present meta-analysis was conducted according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE)guidelines. We conducted a systematic search in PubMed, Embase, and the Cochrane Library to identify studies published between January 1, 2010, and January 31, 2023, using the following terms: "stroke," "alteplase," "doses," "efficacy," "tissue plasminogen activator," "r-tPA," and "safety."Primary efficacyoutcomes included favorable outcomes (Modified Rankin Scale scores of 0-2), while secondary efficacy outcome was all-cause mortality at 90 days. Safety outcomes included asymptomatic intracerebral hemorrhage (ICH)and symptomatic ICH assessed using the National Institute of Neurological Disorders and Stroke (NINDS) study and the Safe Implementation of Thrombolysis in Stroke-Monitoring (SITS-MOST) study. We also compared parenchymal hematomas as safety outcome between the two groups defined by the authors themselves in their research.A totalof 16 studies were included in the present meta-analysis. The meta-analysis did not report any significant difference between low-dose and standard-dose r-tPA in terms of mortality, symptomatic intracranial hemorrhage (SICH), asymptomatic ICH, and parenchymal hematomas. However, the favorable outcome was significantly greater in patients receiving a standard dose of r-tPA.