Intravenous Thrombolysis For Acute Ischemic Stroke Research Articles

The effect of intravenous thrombolysis in stroke patients with unsuccessful thrombectomy.

The benefit of intravenous thrombolysis (IVT) is well established. We aim to study the benefits of IVT in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) who underwent unsuccessful mechanical thrombectomy (MT). We included AIS patients who underwent MT for anterior circulation LVO with failed recanalization (modified treatment in cerebral ischemia [mTICI] score ≤ 2A). Patients who received IVT prior to MT were compared to those who received MT alone. Propensity score matching using demographic, clinical, radiographic and procedural variables was used to match patients with and without IVT. The primary outcome was favorable 90-day good functional outcome (defined as modified Rankin scale of 0-2), and secondary outcomes included intracranial hemorrhage (ICH), symptomatic ICH (sICH), and 90-day mortality. Totally, 610 AIS patients with unsuccessful MT were included. After propensity matching, 219 patients were identified in each group. Median age was 70 years and 73 years in the IVT + MT and MT alone groups, respectively. In the IVT + MT group, final mTICI scores of 0, 1, and 2A were achieved in 92 (42.0%), 33 (15.1%), and 94 (42.9%) patients, respectively, versus 76 (34.7%), 29 (13.2%), and 114 (52.1%) in the MT alone group. The IVT + MT group had greater odds of 90-day good functional outcome (adjusted odds ratio 2.54, 95% confidence interval 1.53-4.32). There were no significant differences in secondary outcomes. IVT is associated with improved functional outcomes in AIS patients with LVO despite unsuccessful MT.

Trends in sex differences of functional outcome after intravenous thrombolysis in patients with acute ischemic stroke.

Intravenous thrombolysis (IVT) is an approved treatment for patients with acute ischemic stroke irrespective of sex. However, the current literature on sex differences in functional outcomes following IVT is inconsistent. So far, a number of studies-including a previous analysis based on data from the Austrian Stroke Unit Registry (ASUR)-detected significant sex-related differences in functional outcome, while others did not report any differences between women and men. In addition, currently there is a lack of data on how sex-related differences evolve over time. To assess time trends of sex-related differences in functional outcome of ischemic stroke in a large nationwide cohort and to investigate associations of patient characteristics with functional outcome post thrombolysis in women and men. These data will offer crucial insights into whether sex differences in functional outcome persist despite the large advances in acute stroke treatment. We analyzed retrospective data of consecutive patients with acute ischemic stroke treated with IVT in 39 stroke centers contributing to the ASUR between 2006 and 2021. We included patients over 18 years of age diagnosed with an acute ischemic stroke who received IVT and with available data on functional outcome at 3 months after treatment. The primary outcome parameter was favorable functional outcome (modified Rankin Scale (mRS) of 0-2) at 3 months. Multivariable logistic regression analysis was performed in the overall population and stratified by sex to assess associations of baseline characteristics with functional outcome. Among 11,840 patients receiving IVT, 2489 of 5503 (45.4%) women achieved favorable functional outcome compared to 3787 of 6337 (59.8%) men. Overall, female sex was a statistically significant predictor of functional outcome after thrombolysis, but additional predictors of outcome differed between women and men. Female sex was independently associated with decreased chances of achieving functional independency (adjusted odds ratio (adjOR) = 0.87, 95% confidence interval (CI) = 0.79-0.96, p = 0.005) and we detected a statistically significant improvement in functional outcome over time only in men (year of treatment, adjOR (per year) = 1.04, 95% CI = 1.02-1.06, p < 0.001) but not in women (adjOR (per year) = 1.01, 95% CI = 0.99-1.03, p = 0.280). Hypertension, smoking, and longer or unknown onset-to-door times were statistically significant predictors of outcome only in male patients, whereas atrial fibrillation, prior myocardial infarction, and longer door-to-needle times were significantly associated with outcome only in women. Sex differences in functional outcome after IVT for acute ischemic stroke are persisting over the past years. Results of our analysis can increase awareness and a resulting focus on sex differences in predictors of outcome could be helpful in mitigating these differences in the future by supporting a more individualized patient care in clinical routine. Follow-up analyses are needed to assess this potential impact and its effect in the future. Data from the Austrian Stroke Unit Registry can only be accessed by the employed statistician (D.M.), access inquiries have to be addressed to the registry's academic review board.

Persistent Inequities in Intravenous Thrombolysis for Acute Ischemic Stroke in the United States: Results From the Nationwide Inpatient Sample.

Despite its approval for acute ischemic stroke >25 years ago, intravenous thrombolysis (IVT) remains underused, with inequities by age, sex, race, ethnicity, and geography. Little is known about IVT rates by insurance status. We assessed temporal trends from 2002 to 2015 in IVT for acute ischemic stroke in the Nationwide Inpatient Sample using adjusted, survey-weighted logistic regression. We calculated odds ratios for IVT for each category in 2002 to 2008 (period 1) and 2009 to 2015 (period 2). IVT use for acute ischemic stroke increased from 1.0% in 2002 to 6.8% in 2015 (adjusted annual relative ratio, 1.15). Individuals aged ≥85 years had the most pronounced increase during 2002 to 2015 (adjusted annual relative ratio, 1.18) but were less likely to receive IVT compared with 18- to 44-year-olds in period 1 (adjusted odds ratio [aOR], 0.23) and period 2 (aOR, 0.36). Women were less likely than men to receive IVT, but the disparity narrowed over time (period 1: aOR, 0.81; period 2: aOR, 0.94). Inequities in IVT resolved for Hispanic individuals in period 2 (aOR, 0.96) but not for Black individuals (period 2: aOR, 0.81). The disparity in IVT for Medicare patients, compared with privately insured patients, lessened over time (period 1: aOR, 0.59; period 2: aOR, 0.75). Patients treated in rural hospitals remained less likely to receive IVT than in urban hospitals; a more dramatic increase in urbanity widened the inequity (period 2, urban nonteaching versus rural: aOR, 2.58, period 2, urban teaching versus rural: aOR, 3.90). IVT for acute ischemic stroke increased among adults. Despite some encouraging trends, the remaining disparities highlight the need for intensified efforts at addressing inequities.

A weakly supervised deep learning model integrating noncontrasted computed tomography images and clinical factors facilitates haemorrhagic transformation prediction after intravenous thrombolysis in acute ischaemic stroke patients

BackgroundHaemorrhage transformation (HT) is a serious complication of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS). Accurate and timely prediction of the risk of HT before IVT may change the treatment decision and improve clinical prognosis. We aimed to develop a deep learning method for predicting HT after IVT for AIS using noncontrast computed tomography (NCCT) images.MethodsWe retrospectively collected data from 828 AIS patients undergoing recombinant tissue plasminogen activator (rt-PA) treatment within a 4.5-h time window (n = 665) or of undergoing urokinase treatment within a 6-h time window (n = 163) and divided them into the HT group (n = 69) and non-HT group (n = 759). HT was defined based on the criteria of the European Cooperative Acute Stroke Study-II trial. To address the problems of indiscernible features and imbalanced data, a weakly supervised deep learning (WSDL) model for HT prediction was constructed based on multiple instance learning and active learning using admission NCCT images and clinical information in addition to conventional deep learning models. Threefold cross-validation and transfer learning were performed to confirm the robustness of the network. Of note, the predictive value of the commonly used scales in clinics associated with NCCT images (i.e., the HAT and SEDAN score) was also analysed and compared to measure the feasibility of our proposed DL algorithms.ResultsCompared to the conventional DL and ML models, the WSDL model had the highest AUC of 0.799 (95% CI 0.712–0.883). Significant differences were observed between the WSDL model and five ML models (P < 0.05). The prediction performance of the WSDL model outperforms the HAT and SEDAN scores at the optimal operating point (threshold = 1.5). Further subgroup analysis showed that the WSDL model performed better for symptomatic intracranial haemorrhage (AUC = 0.833, F1 score = 0.909).ConclusionsOur WSDL model based on NCCT images had relatively good performance for predicting HT in AIS and may be suitable for assisting in clinical treatment decision-making.

Association between infarct location and haemorrhagic transformation of acute ischaemic stroke after intravenous thrombolysis

To evaluate the association between computed tomography (CT)-based imaging variables at the time of admission and haemorrhagic transformation (HT) after intravenous thrombolysis (IVT). One hundred and eight patients who were treated with IVT for acute ischaemic stroke (AIS) during January 2021 to July 2023 were analysed retrospectively. The infarct location was classified as cortical or subcortical in accordance with the Alberta Stroke Program Early CT Score (ASPECTS) system. Logistic regression and receiver operating characteristic curve analyses were performed to determine the relationship between ischaemic variables and HT. Of the total, 18 (16.7%) patients had HT and seven (6.5%) had symptomatic intracerebral haemorrhage (sICH). Multivariate analysis revealed that cortical ASPECTS was independently associated with HT (odds ratio [OR], 0.197; 95% confidence interval [CI], 0.076-0.511; p=0.001) and cortical ASPECTS was independently associated with sICH (OR, 0.066; 95% CI, 0.009-0.510; p=0.009). To predict HT and sICH, cortical ASPECTS (HT area under the curve [AUC]=0.881, sICH AUC=0.971) provided a higher AUC compared with ASPECTS (HT AUC=0.850, sICH AUC=0.918). Cortical ASPECTS seen on CT at the time of admission is associated with HT and sICH after IVT.

The association between monocyte to high-density lipoprotein cholesterol ratio and clinical prognosis of acute ischemic stroke after intravenous thrombolysis therapy.

The monocyte-to-high-density lipoprotein cholesterol (HDL) ratio (MHR) is accepted as a novel marker for demonstrating inflammation. We investigated whether the monocyte-to-HDL ratio is related to the 90-day clinical prognosis of acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). Patients with AIS treated with alteplase IVT were included consecutively, and clinical information and laboratory data were collected. The 90-day prognosis of all patients was determined with a clinical assessment using the modified Rankin Scale (mRS). The optimal cutoff values for patients were evaluated by the receiver operating characteristic (ROC) curve method. Then, a multivariate logistic regression model was used to evaluate the risk factors for poor prognosis of IVT in AIS. We retrospectively enrolled 192 patients who were diagnosed with AIS and received IVT between February 2020 and July 2022, with final follow-up on September 30, 2022. The patients in the poor prognosis group had significantly higher monocyte counts, lower HDL levels, and higher MHR values than the good prognosis group. The optimal cutoff value of the MHR for predicting the 3-month outcome of acute pontine infarction was 0.621. Multivariate logistic regression revealed that the MHR (OR = 4.626, 95% CI: 1.156-18.512, P = .030) was strongly associated with poor prognosis in AIS. The MHR is an independent risk factor for the clinical prognosis of AIS patients receiving IVT therapy and shows a certain predictive value.

Impact of smoking on outcomes following endovascular therapy for acute ischemic stroke: A systematic review and meta-analysis.

Smoking represents a leading risk factor for acute ischemic stroke (AIS). Previous literature has described a "smoking paradox", wherein smokers experience better outcomes following intravenous thrombolysis for AIS. It is unclear whether such a phenomenon exists in smokers undergoing endovascular therapy (EVT) for AIS. To assess outcomes in smokers following EVT for AIS, we conducted a systematic review and meta-analysis. Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Embase Web of Science, and Scopus. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0-2, thrombolysis in cerebral infarction (TICI) score 2b-3, symptomatic intracranial hemorrhage (sICH), and mortality. We calculated mean difference (MD), pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). Eight studies with 2633 patients comprised our analysis. On average, smokers were 10.14 years (MD = 10.14, [95% CI = -14.49 to -5.79], P-value < 0.001) younger than non-smokers. Smokers achieved mRS 0-2 (OR = 1.82, [95% CI, 1.34-2.48], P-value < 0.001) and TICI 2b-3 (OR = 1.61, [95% CI, 1.19-2.19], P-value = 0.002) at a higher rate than non-smokers. sICH rates were comparable between smokers and non-smokers (OR = 1.07, [95% CI, 0.62-1.85], P-value = 0.81). Smokers had a lower rate of 90-day mortality than non-smokers (OR = 0.54, [95% CI, 0.41-0.71], P-value < 0.001). In this meta-analysis of eight studies, we found that smokers with AIS undergoing EVT experienced better 90-day outcomes and higher rates of TICI 2b-3. This may be due to baseline differences between smokers and non-smokers, but future studies should explore alternative reasons that could explain this relationship between smoking and AIS treated with EVT.

P.065 Comparison in outcomes by sex in acute ischemic stroke patients treated with alteplase versus tenecteplase: a subgroup analysis of AcT

Background: Sex differences in treatment response to intravenous thrombolysis (IVT) are poorly characterized. We compared sex-disaggregated outcomes in patients receiving IVT for acute ischemic stroke in the Alteplase compared to Tenecteplase (AcT) trial, a Canadian multicentre, randomised trial. Methods: In this post-hoc analysis, the primary outcome was excellent functional outcome (modified Rankin Score [mRS] 0-1) at 90 days. Secondary and safety outcomes included return to baseline function, successful reperfusion (eTICI≥2b), death and symptomatic intracerebral hemorrhage. Results: Of 1577 patients, there were 755 women and 822 men (median age 77 [68-86]; 70 [59-79]). There were no differences in rates of mRS 0-1 (aRR 0.95 [0.86-1.06]), return to baseline function (aRR 0.94 [0.84-1.06]), reperfusion (aRR 0.98 [0.80-1.19]) and death (aRR 0.91 [0.79-1.18]). There was no effect modification by treatment type on the association between sex and outcomes. The probability of excellent functional outcome decreased with increasing onset-to-needle time. This relation did not vary by sex (pinteraction 0.42). Conclusions: The AcT trial demonstrated comparable functional, safety and angiographic outcomes by sex. This effect did not differ between alteplase and tenecteplase. The pragmatic enrolment and broad national participation in AcT provide reassurance that there do not appear to be sex differences in outcomes amongst Canadians receiving IVT.

Reasons for Exclusion From Intravenous Thrombolysis in Acute Ischemic Stroke: Experience From a Moroccan Stroke Unit.

Background and objective The rate of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) is still low due to several absolute and relative contraindications, including admission time delay, which remains the main reason for exclusion from thrombolysis. In this study, we aimed to identify reasons for non-thrombolysis at our stroke center. Methods This retrospective study included all patients with a final diagnosis of AIS as per our stroke prospective register from 2014 to 2019. Reasons for non-thrombolysis were analyzed for all AISand for patients admitted within 4.5 hours from symptom onset. From 2014 to 2016, a non-contrast CT scan was the unique imaging modality used to decide on performing IVT. In 2017, CT angiography was added to the imaging protocol. Results Among 3,562 patients with AIS, 3,365 (94.4%) were excluded from thrombolysis; 2,871 (80.6%) were admitted out of the IVT time window, which represents the main reason for exclusion from thrombolysis. Thrombolysis alert (TA) was triggered for 691 (19.4%) patients, and 197 patients had IVT (which represents 28.5% of TA and 5.5% of all AIS). Minor stroke and rapidly improving symptoms of stroke were alsoreasons for non-thrombolysis, which explain the high-averageinitial National Institutes of Health Stoke Scale (NIHSS) score of more than 12 in the thrombolysis group. CT angiographyallows for the analysis of the supra-aortic trunks, the circle of Willis, and the collateral status. Therefore, during the period when a CT angiography scan was used, there were more IVTs for minor strokes, rapidly improving strokes, and AIS patients admitted beyond the IVT time window. Conclusions This study highlights the common reasons for exclusion from thrombolysis. Efforts should be undertaken to avoid admissiontime delays. Also, based on our findings, minor stroke and improving stroke no longer represent absolutecontraindications for IVT in AIS.

Tirofiban for Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis: A Systematic Review and Meta-Analysis

Introduction: Tirofiban has been used as a rescue when thrombectomy is not successful in endovascular therapy (EVT) for acute ischemic stroke (AIS), but the use of tirofiban after intravenous thrombolysis (IVT) is controversial. The purpose of this meta-analysis was to evaluate the safety and efficacy of tirofiban combined with IVT in AIS compared with not receiving tirofiban. Methods: The PubMed and Embase databases were searched for all relevant studies published up to August 31, 2021. The safety endpoints included symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage (ICH), and mortality. The efficacy endpoint was the modified Rankin Scale (mRS) score at the 3-month follow-up. Results: Seven articles (1,036 patients) were included. Of these, 444 patients received tirofiban, and 592 patients did not. Meta-analysis showed that tirofiban did not increase the risk of sICH (OR 0.98; 95% CI 0.50–1.93; p = 0.96), any ICH (OR 0.94; 95% CI 0.63–1.39; p = 0.75) or mortality (OR 0.67; 95% CI 0.39–1.15; p = 0.15) and tended to be associated with a favorable functional outcome (OR 1.33; 95% CI 0.99–1.78; p = 0.06) in patients with AIS. Subgroup analysis showed that bridging therapy combined with tirofiban could reduce mortality (OR 0.47; 95% CI 0.23–0.98; p = 0.04). Tirofiban significantly improved the favorable functional outcome in patients with IVT only (non-EVT) (OR 1.98; 95% CI 1.30–3.02; p = 0.002). Conclusion: Intravenous tirofiban could be safe for patients with AIS undergoing IVT, regardless of receiving EVT. Intravenous tirofiban may reduce mortality rates for patients undergoing bridging therapy. It also could increase the likelihood of a favorable functional outcome, especially for patients receiving IVT only.

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with End-Stage Renal Disease on Hemodialysis: A Narrative Review.

Acute ischemic stroke (AIS) is a significant and devastating complication in patients with end-stage renal disease on hemodialysis (ESRD/HD). Since one-third of AIS in ESRD/HD patients occurs during or soon after dialysis, patients are more likely to present within the time window when intravenous thrombolysis (IVT) can be performed. IVT may improve prognosis in ESRD/HD patients with AIS. However, ESRD/HD patients have been excluded from large trials and may have been withheld from IVT due to concerns about bleeding complications. To date, there is no clear evidence and firm guidance on the safety and efficacy of IVT in ESRD/HD patients with AIS. This narrative review aimed to evaluate critical scientific data on the benefits and risks of IVT use in patients with ESRD/HD and AIS. We searched the electronic database of PubMed for studies evaluating the relationship between AIS, ESRD/HD, and IVT. Reference sections and additional publications were also searched manually. Studies on AIS in patients with ESRD/HD requiring maintenance dialysis that referred to IVT were included. In total, 560 studies were found in the PubMed electronic database during the period covered, of which 10 met the selection criteria. IVT for AIS in ESRD/HD patients could improve neurological outcomes and be safely performed even with the possibility of hemorrhagic complications associated with hypertension. Despite the high complication and mortality rates in ESRD/HD patients with AIS after IVT, the association with IVT was unclear. IVT for AIS in ESRD/HD patients may improve outcomes and should not be withheld based solely on ESRD/HD status.

Temporal Trends of Intravenous Thrombolysis Utilization in Acute Ischemic Stroke in a Prospective Cohort From 1998 to 2019: Modeling Based on Joinpoint Regression.

IntroductionThe frequency of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) is lower than it should be in several regions of the world. It is unclear what interventions can produce significant improvements in IVT utilization. We aimed to investigate the temporal trends in IVT in AIS and identify changes in time that could be associated with specific interventions.MethodsWe included patients with AIS who were admitted from January 1998 to December 2019 in our institution. To analyze trends in utilization and time points in which they changed, we performed a Joinpoint regression analysis. Interventions were assigned to a specific category according to the Behavior Change Wheel framework intervention function criteria.ResultsA total of 3,361 patients with AIS were admitted, among which 538 (16%) received IVT. There were 245 (45.5%) women, and the mean age and median National Institutes of Health Stroke Scale (NIHSS) scores were 68.5 (17.2) years and 8 (interquartile range, 4–15), respectively. Thrombolysis use significantly increased by an average annual 7.6% (95% CI, 5.1–10.2), with one Joinpoint in 2007. The annual percent changes were.45% from 1998 to 2007 and 9.57% from 2007 to 2019, concurring with the stroke code organization, the definition of door-to-needle times as an institutional performance measure quality indicator, and the extension of the therapeutic window.ConclusionsThe IVT rates consistently increased due to a continuous process of protocol changes and multiple interventions. The implementation of a complex multidisciplinary intervention such as the stroke code, as well as the definition of a hospital quality control metric, were associated with a significant change in this trend.

High glycemic albumin representing prestroke glycemic variability is associated with hemorrhagic transformation in patients receiving intravenous thrombolysis

We evaluated the impact of prestroke glycemic variability estimated by glycated albumin (GA) on symptomatic hemorrhagic transformation (SHT) in patients with intravenous thrombolysis (IVT). Using a multicenter database, we consecutively enrolled acute ischemic stroke patients receiving IVT. A total of 378 patients were included in this study. Higher GA was defined as GA ≥ 16.0%. The primary outcome measure was SHT. Multivariate regression analysis and a receiver operating characteristic curve were used to assess risks and predictive ability for SHT. Among the 378 patients who were enrolled in this study, 27 patients (7.1%) had SHT as defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SHTSITS). The rate of SHTSITS was higher in the higher GA group than in the lower GA group (18.0% vs. 1.6%, p < 0.001). A higher GA level (GA ≥ 16.0%) significantly increased the risk of SHTSITS (adjusted odds ratio [OR], [95% confidence interval, CI], 12.57 [3.08–41.54]) in the logistic regression analysis. The predictive ability of the GA level for SHTSITS was good (AUC [95% CI]: 0.83 [0.77–0.90], p < 0.001), and the cutoff value of GA in SHT was 16.3%. GA was a reliable predictor of SHT after IVT in acute ischemic stroke in this study.

Predictors for symptomatic intracranial hemorrhage after intravenous thrombolysis with acute ischemic stroke within 6\u2009h in northern China: a multicenter, retrospective study

Background and purposeThis study assessed the predictive factors for symptomatic intracranial hemorrhage (sICH) in patients with acute ischemic stroke (AIS) after receiving intravenous thrombolysis (IVT) within 6 h in northern China.MethodsWe retrospectively analyzed ischemic stroke patients who were treated with IVT between November 2016 and December 2018 in 19 hospitals in Shandong Province, China. Potential predictors of sICH were investigated using univariate and multivariate analyses.ResultsOf the 1293 enrolled patients (845 men, aged 62 ± 11 years), 33 (2.6%) developed sICH. The patients with sICH had increased coronary heart disease (36.4% vs. 13.7%, P = 0.001), more severe stroke (mean National Institutes of Health Stroke Scale [NIHSS] score on admission of 14 vs.7, P < 0.001), longer door-to-needle time [DNT] (66 min vs. 50 min, P < 0.001), higher blood glucose on admission, higher white blood cell counts (9000/mm3 vs. 7950/mm3, P = 0.004) and higher neutrophils ratios (73.4% vs. 67.2%, P = 0.006) et al. According to the results of multivariate analysis, the frequency of sICH was independently associated with the NIHSS score (OR = 3.38; 95%CI [1.50–7.63]; P = 0.003), DNT (OR = 4.52; 95%CI [1.69–12.12]; P = 0.003), and white blood cell count (OR = 3.59; 95%CI [1.50–8.61]; P = 0.004).When these three predictive factors were aggregated, compared with participants without any factors, the multi-adjusted odds ratios (95% confidence intervals) of sICH for persons concurrently having one, two or three of these factors were 2.28 (0.25–20.74), 15.37 (1.96–120.90) and 29.05 (3.13–270.11), respectively (P for linear trend < 0.001), compared with participants without any factors.ConclusionNIHSS scores higher than 10 on admission, a DNT > 50 min, and a white blood cell count ≥9000/mm3 were independent risk factors for sICH in Chinese patients within 6 h after IVT for AIS.

Intravenous Thrombolysis by Telestroke in the 3- to 4.5-h Time Window.

Background: While intravenous thrombolysis (IVT) in ischemic stroke can be safely applied in telestroke networks within 3 h from symptom onset, there is a lack of evidence for safety in the expanded 3- to 4. 5-h time window. We assessed the safety and short-term efficacy of IVT in acute ischemic stroke (AIS) in the expanded time window delivered through a hub-and-spoke telestroke network.Methods: Observational study of patients with AIS who received IVT at the Stroke Eastern Saxony Telemedical Network between 01/2014 and 12/2015. We compared safety data including symptomatic intracerebral hemorrhage (sICH; according to European Cooperative Acute Stroke Study II definition) and any intracerebral hemorrhage (ICH) between patients admitted to telestroke spoke sites and patients directly admitted to a tertiary stroke center representing the hub of the network. We also assessed short-term efficacy data including favorable functional outcome (i.e., modified Rankin Scale ≤ 2) and National Institutes of Health Stroke Scale (NIHSS) at discharge, hospital discharge disposition, and in-hospital mortality.Results: In total, 152 patients with AIS were treated with IVT in the expanded time window [spoke sites, n = 104 (26.9%); hub site, n = 48 (25.9%)]. Patients treated at spoke sites had less frequently a large vessel occlusion [8/104 (7.7) vs. 20/48 (41.7%); p < 0.0001], a determined stroke etiology (p < 0.0001) and had slightly shorter onset-to-treatment times [210 (45) vs. 228 (58) min; p = 0.02] than patients who presented to the hub site. Both cohorts did not display any further differences in demographics, vascular risk factors, median baseline NIHSS scores, or median baseline Alberta stroke program early CT score (p > 0.05). There was no difference in the frequency of sICH (4.9 vs. 6.3%; p = 0.71) or any ICH (8.7 vs. 16.7%; p = 0.15). Neither there was a difference regarding favorable functional outcome (44.1 vs. 39.6%; p = 0.6) nor median NIHSS [3 (5.5) vs. 2.5 (5.75); p = 0.92] at discharge, hospital discharge disposition (p = 0.28), or in-hospital mortality (9.6 vs. 8.3%; p = 1.0). Multivariable modeling did not reveal an association between telestroke and sICH or favorable functional outcome (p > 0.05).Conclusions: Delivery of IVT in the expanded 3- to 4.5-h time window through a telestroke network appears to be safe with equivalent short-term functional outcomes for spoke-and-hub center admissions.

Short- and long-term mortality after intravenous thrombolysis for acute ischemic stroke: A propensity score-matched cohort with 5-year follow-up.

It remains unknown whether intravenous thrombolysis (IVT), thrombectomy, or poststroke antithrombotic medication lower short- and long-term mortality in acute ischemic stroke (AIS). This study aimed to investigate the efficacy of IVT in AIS using propensity score matching, to determine whether IVT could reduce short- and long-term mortality, and to identify risk factors influencing short- and long-term mortality in AIS.During 2013 to 2014, the nationwide Korea Acute Stroke Assessment registry enrolled 14,394 patients with first-ever recorded ischemic stroke. Propensity score matching was used to match IVT and control cases with a 1:1 ratio. The primary outcome was survival up to 3 months, 1 year, and 5 years, as assessed using Kaplan–Meier estimates and Cox proportional hazards.In total, 1317 patients treated with IVT were matched with 1317 patients not treated with IVT. Survival was higher in the IVT group (median, 3.53 years) than in the non-IVT group (median, 3.37 years, stratified log-rank test, P < .001). Compared with the non-IVT group, thrombolysis performed within 2 hours significantly reduced the risk of 3-month mortality by 37%, and thrombolysis performed between 2 and 4.5 hours significantly reduced the risk of 3-month mortality by 26%. Thrombectomy significantly reduced the risk of 3-month mortality by 28%. Compared with no poststroke medication, poststroke antiplatelet medication was associated with 51%, 55%, and 52% decreases in 3-month, 1-year, and 5-year mortality risk, respectively. Poststroke anticoagulant medication was associated with 51%, 54%, and 44% decreases in the risk of 3-month, 1-year, and 5-year mortality, respectively.IVT and mechanical thrombectomy showed improvement in short-term survival. To improve long-term outcomes, the use of poststroke antithrombotic medication is important in AIS.

Hyperdense middle cerebral artery sign and response to combination of mechanical Thrombectomy plus intravenous thrombolysis in acute stroke patients

Background and purposeCombining intra-arterial mechanical thrombectomy (IAMT) and intravenous thrombolysis (IVT) has shown to have an excellent recanalization rate and better clinical outcome in acute ischemic stroke (AIS) patients. Hyperdense middle cerebral artery sign (HMCAS) on pretreatment non-contrast head CT scan of AIS patients is one of the early ischemic radiological findings in middle cerebral artery territory AIS. We aimed to evaluate whether the presence of HMCAS predicts the outcome of AIS patients receiving combination therapy with IAMT and IVT. MethodsWe retrospectively reviewed medical records and cerebrovascular images of the patients treated with IAMT and IVT for AIS in our center. Patients with occlusion in the terminal internal carotid artery or middle cerebral artery on pretreatment CT angiogram of the head were included. Clinical outcome was compared between subjects with HMCAS and those without. Modified Rankin Score (mRS) and symptomatic intracranial hemorrhage (sICH) were used as measures of efficacy and safety, respectively. ResultsOf 93 patients, 46 (49%) had HMCAS on their initial head CT scan. Both groups had comparable baseline characteristics and stroke severity. After adjusting for age, NIHSS score, time from symptom onset to starting IVT, and history of diabetes mellitus in multivariate logistic regression analysis, there was no difference in terms of a poor outcome (mRS >2) (OR = 0.5 [CI 0.2–1.4], p = 0.188) or rate of sICH (OR = 3.3 [CI 0.6–19.0], p = 0.190) between the two groups. ConclusionsHMCAS is not a predictor of poor outcome in AIS patients receiving combination therapy with IAMT and IVT and does not affect treatment safety.

Fibrinogen depletion and intracerebral hemorrhage after thrombolysis for ischemic stroke: a meta-analysis.

Intracerebral hemorrhage (ICH) can be a fatal complication of intravenous thrombolysis (IVT) for acute ischemic stroke. An early coagulopathy can develop after IVT, in relation to a significant fibrinogen depletion, increasing the risk of ICH. This systematic review and meta-analysis aimed at defining the role of fibrinogen depletion after IVT on the risk of ICH after IVT. Protocol was registered with PROSPERO (CRD42020124241) and followed PRISMA and MOOSE guidelines. We systematically searched English studies reporting rates of post-IVT ICH depending on fibrinogen depletion until 7/1/2021. Primary outcome was symptomatic ICH (sICH). Meta-analysis followed random-effects model to account for heterogeneity in design and timing of ascertainments. Biases were assessed via the Newcastle-Ottawa Scale. Overall, among 352 records identified, 5 observational studies were eligible for quantitative synthesis (n = 2142), all of fair quality. Considering sICH within 24-36h post-IVT, pooling data from 4 studies (n = 1753), fibrinogen depletion consistently increased the risk of sICH (OR 3.67, 95%CI 2.28-5.90, pheterogeneity = 0.55). Pooling adjusted estimated for age, gender, and NIHSS from 3 studies (n = 723), fibrinogen depletion was confirmed to significantly increase the risk of ICH after IVT (OR 5.41, 95%CI 2.96-9.89). Fibrinogen depletion significantly increases the risk of ICH after IVT for acute ischemic stroke. Routine fibrinogen assessment might be considered to identify people at higher risk of ICH. As fibrinogen repletion is feasible, trials should investigate its efficacy in preventing ICH, potentially increasing the net benefit profile of IVT in acute ischemic stroke.

Abstract P872: Persistent Inequities in Intravenous Thrombolysis for Acute Ischemic Stroke in the United States: Results From the Nationwide Inpatient Sample

Background: Intravenous thrombolysis (IVT) was approved for acute ischemic stroke (AIS) 25 yrs ago, yet few AIS patients receive it, with inequities by race/ethnicity, sex, and geography. With expanding evidence-based programs, we hypothesized increases in IVT utilization and reduction in inequities. Methods: Using the Nationwide Inpatient Sample (NIS), we assessed temporal trends from 2002 to 2015 in IVT for AIS (weighted N=6,694,081) by sex, race/ethnicity, age, insurance, and hospital location/teaching status strata using survey - weighted logistic regression. Covariates included socio-demographics, comorbidities, and hospital characteristics. We calculated odds ratios for IVT by each category in 2002-2008 and 2009-2015. Results: IVT for AIS increased from 1.0% in 2002 to 6.8% in 2015, with an overall adjusted annual relative ratio (AARR) of 1.15 (CI 1.14-1.16). Individuals 18-44 yrs had the highest rate of IVT in 2015. The very elderly (≥85 yrs) had the most pronounced increase in IVT (AARR 1.18, CI 1.17-1.19). The sex disparity in IVT improved, but in 2009-2015, women were still 6% less likely to receive IVT than men (Fig 1). Individuals 18-44 yrs were ~3-fold more likely to receive IVT than the very elderly. IVT inequities for black and Hispanic stroke survivors lessened, but blacks remained ~20% less likely than whites to receive IVT. Government-insured patients were ~25% less likely to receive IVT compared to privately insured. Urban AIS patients were up to 4-fold more likely to receive IVT than rural dwellers. Conclusion: From 2002 through 2015, IVT for AIS in the U.S. increased regardless of race/ethnicity, sex, and age among ≥18 yrs, with the most pronounced increase among the very elderly. Despite encouraging trends, only 1 in 15 AIS patients received IVT and persistent inequities remain for blacks, women, government-insured, and rural stroke survivors, highlighting the need for intensifying stroke literacy and preparedness and enhancing systems of care.

Recent silent infarcts do not increase the risk of haemorrhage after intravenous thrombolysis

Haemorrhagic transformation (HT) is one of the main risks of intravenous thrombolysis (IVT) for acute ischaemic stroke. Contraindications serve to exclude patients at high risk of HT after IVT. One of these contraindications is a stroke within the preceding 3months. It is unclear if this contraindication should include recent clinically silent infarcts (RSIs). The aim of this study was to investigate whether RSIs are associated with a higher risk of HT and a worse clinical outcome after IVT for acute ischaemic stroke. In a retrospective monocentric cohort study, all patients who received IVT for acute ischaemic stroke based on magnetic resonance imaging were assessed over 5years. RSIs were defined as lesions with diffusion restriction and positive signal on fluid attenuated inversion recovery sequences. Patients with RSIs (RSI+) were compared to patients without RSIs (RSI-) regarding HT after IVT and clinical outcome. In all, 981 patients who had received IVT for acute ischaemic stroke demonstrated by magnetic resonance imaging were identified. RSIs were detected in 115 patients (11.5%). HT after IVT was observed in 32 (28.3%) RSI+ and 56 (25.8%) RSI- patients (P=0.624). Symptomatic intracerebral haemorrhage was noted in two (1.8%) RSI+ and five (2.3%) RSI- patients (P=1.000). No differences in clinical outcome were observed. The detection of RSIs in patients treated with IVT for acute ischaemic stroke was not associated with a higher risk of HT or a worse clinical outcome. The results of this study argue against considering RSIs as a contraindication for IVT.