Intravenous Alteplase Research Articles

Systemic Thrombolytic Therapy for Massive and Submassive Pulmonary Embolism

Objective: To critically evaluate the published literature assessing the safety and efficacy of thrombolytic therapy for massive and submassive pulmonary embolism (PE). Methods: A search of human trials in the English-language (September 2017) was conducted through the MEDLINE database using the following terms: PE, tissue plasminogen activator, tenecteplase, and alteplase. 67 unique articles were identified, of which 24 clinical trials discussing clinical outcomes related to administration of either intravenous tenecteplase or alteplase were included. Results: Thrombolytic therapy with anticoagulation significantly reduced mortality compared to anticoagulation alone in massive PE. In submassive PE, thrombolytics reduced the rate of right ventricular dysfunction and hemodynamic collapse; however, there is an increased risk of major and minor bleeding with no benefit on long-term functional outcomes. Conclusions: Patients with massive PE should receive thrombolytics when no major contraindications to therapy exist. Patients with submassive PE at highest risk for progression to hemodynamic instability should receive anticoagulation and be monitored for clinical deterioration. If an imminent risk of hemodynamic instability or cardiac arrest occurs, thrombolytics should be administered if no contraindications exist. Net mortality benefit and risk of bleeding must be considered when deciding to administer thrombolytic therapy in massive or submassive PE.

Impaired fasting glucose is associated with unfavorable outcome in ischemic stroke patients treated with intravenous alteplase.

Hyperglycemia on admission and diabetes mellitus type II are associated with unfavorable outcome in stroke patients. We studied whether impaired fasting glucose (IFG) is associated with unfavorable outcome in ischemic stroke patients treated with intravenous alteplase as well and if IFG is a stronger prognostic factor than hyperglycemia on admission. We studied 220 consecutive patients with ischemic stroke treated with intravenous alteplase. In all nondiabetic patients, fasting glucose was determined on day 2-5. IFG was defined as fasting glucose level of ≥ 5.6mmol/L, hyperglycemia on admission as glucose levels ≥ 7.9mmol/L. The primary effect measure was the adjusted common odds ratio (acOR) for a shift in the direction of worse outcome on the modified Rankin Scale at 3months, estimated with ordinal logistic regression, and adjusted for common prognostic factors. The fasting glucose levels were available in 194 and admission glucose levels in 215 patients. Sixty-three (32.5%) had IFG, 58 (27%) hyperglycemia on admission and 32 (14.6%) pre-existent diabetes. Patients with IFG showed a shift towards worse functional outcome compared with patients with normal fasting glucose levels (acOR 2.77; 95% CI 1.54-4.97), which was stronger than hyperglycemia on admission (acOR 1.75; 95% CI 0.91-3.4). IFG is associated with unfavorable outcome after treatment with intravenous alteplase for acute ischemic stroke. IFG predicts unfavorable outcome better than hyperglycemia on admission.

Adrenal hormones and circulating leukocyte subtypes in stroke patients treated with reperfusion therapy

Ischemic stroke sets in motion a dialogue between the central nervous and the immune systems that includes the sympathetic/adrenal system. We investigated the course of immune cells and adrenocortical and adrenomedullary effectors in a cohort of 51 patients with acute stroke receiving reperfusion therapy (intravenous alteplase or mechanical thrombectomy) and its correlation with stroke outcomes and infarct growth. Cortisol increased rapidly and fleetingly after stroke, but 39% of patients who had larger infarctions on admission showed a positive delta cortisol at day 1. It was associated with enhanced infarct growth (p = 0.002) and poor outcome [OR (95% CI) 5.30 (1.30–21.69)], and correlated with less lymphocytes and T cells at follow up. Likewise, fewer circulating lymphocytes, T cells, and Tregs were associated with infarct growth. By contrast, metanephrines did not increase at clinical onset, and decreased over time. Higher levels of NMN correlated with more Treg and B cells. Eventually, complete reperfusion at the end of therapy headed the identification of more circulating Tregs at day 1. Then activation of cortical or medullar compartments of the adrenal gland result in specific signatures on leukocyte subpopulations. Manipulation of the adrenal gland hormone levels warrants further investigation.

Tenecteplase versus Alteplase for the Management of Acute Ischemic Stroke in a Low-income Country-Nepal: Cost, Efficacy, and Safety.

Intravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered, mutant tissue plasminogen activator, is an alternative thrombolytic agent. The economic feasibility of stroke treatment has been a matter of huge debate and discussion thus far. The use of thrombolytics for the management of ischemic stroke has recently begun in Nepal. In low-income countries like Nepal, where the per capita income falls at just $691.7 and 25.2% of the population are under the poverty line, stroke patients cannot meet treatment expenses. Tenecteplase is easily available (for the management of acute coronary syndrome) in tertiary-level hospitals of Nepal and the price quote of tenecteplase ($450) is half the price of alteplase ($1000). In emergency cases, sometimes, the cost of alteplase can be greater than the patient can afford and they can't undergo thrombolysis even after arriving on time. However, evidence exists that supports the use of other alternatives (tenecteplase), which are also effective in the management of acute ischemic stroke. In this article, we examined current evidence for the efficacy and safety of tenecteplase when compared to alteplase. This review will make neurologists in Nepal familiar with the efficacy and safety of tenecteplase in comparison with alteplase since it is common for patients to not be able to afford the expensive alteplase, which makes guideline-based practice impossible some times.

Cerebral Microbleeds are an Independent Predictor of Hemorrhagic Transformation Following Intravenous Alteplase Administration in Acute Ischemic Stroke

Intravenous alteplase (rt-PA) increases the risk of hemorrhagic transformation of acute ischemic stroke. The objective of our study was to evaluate clinical, laboratory, and imaging predictors on forecasting the risk of hemorrhagic transformation following treatment with rt-PA. We also evaluated the factors associated with cerebral microbleeds that increase the risk of hemorrhagic transformation. Consecutive patients with acute ischemic stroke admitted between January 1, 2009 and December 31, 2013 were included in the study if they received IV rt-PA, had magnetic resonance imaging (MRI) of the brain on admission, and computed tomography or MRI of the brain at 24 (18-36) hours later to evaluate for the presence of hemorrhagic transformation. The clinical data, lipid levels, platelet count, MRI, and computed tomography images were retrospectively reviewed. The study included 366 patients, with mean age 67 ± 15 years; 46% were women and 88% were white. The median National Institutes of Health Stroke Scale (NIHSS) score was 6 (interquartile range 3-15). Hemorrhagic transformation was observed in 87 (23.8%) patients and cerebral microbleeds were noted in 95 (25.9%). Patients with hemorrhagic transformation tended to be older, nonwhite, have atrial fibrillation, higher baseline NIHSS score, lower cholesterol and triglyceride levels, and cerebral microbleeds and nonlacunar infarcts. Patients with cerebral microbleeds were more likely to be older, have hypertension, hyperlipidemia, previous history of stroke, and prior use of antithrombotics. On multivariate analysis race, NIHSS score, nonlacunar infarct, and presence of cerebral microbleeds were independently associated with hemorrhagic transformation following treatment with rt-PA. Presence of cerebral microbleeds is an independent predictor of hemorrhagic transformation of acute ischemic stroke following treatment with rt-PA.

Thrombolysis in Large Diffusion-Weighted Imaging Lesions: Lower Chance but Still a Chance

We sought to investigate whether early thrombolytic treatment can result in favorable functional outcome even in patients with large diffusion-weighted imaging (DWI) lesions. We analyzed 566 patients who received intravenous alteplase within 4.5 hours from onset, initially underwent DWI and magnetic resonance angiography, and had acute infarction confined to anterior circulation. DWI lesion volumes were measured semiautomatically. The association between DWI lesion volume and 3-month outcome in patients who achieved early recanalization was assessed. The DWI lesion volume cutoff, which predicts unfavorable outcome despite recanalization, was determined. In patients with large DWI lesions, the distributions of modified Rankin Scale (mRS) score were compared according to the recanalization status. Four hundred thirty-six patients achieved early recanalization. Among these patients, 283 (65%) patients had a favorable functional outcome (mRS score 0-2). DWI lesion volume (odds ratio [OR], 1.38 per 10 mL; 95% confidence interval [CI], 1.22-1.56) was an independent variable associated with poor outcome, along with hypertension (OR, 1.87; 95% CI, 1.12-3.10), National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.13; 95% CI, 1.08-1.19), and onset-to-needle time (OR, 1.08 per 10 minutes; 95% CI, 1.03-1.13). The DWI lesion of 60 mL or higher highly predicted an unfavorable outcome with a positive predictive value of 95.3%. In patients with a DWI lesion of 60 mL or higher, recanalization had no benefit for an mRS score of 0-2 but was significantly associated with an mRS score of 0-3 (OR, 4.64; 95% CI, 1.08-19.97). Despite early recanalization, the probability of favorable outcome is low in patients with a DWI lesion of 60 mL or higher. Nevertheless, the benefit of recanalization still persists in large DWI lesions.

Low- versus Standard-Dose Intravenous Alteplase in the Context of Bridging Therapy for Acute Ischemic Stroke: A Korean ENCHANTED Study.

Background and PurposeFollowing the positive results from recent trials on endovascular therapy (EVT), bridging therapy (intravenous alteplase plus EVT) is increasingly being used for the treatment of acute ischemic stroke. However, the optimal dose of intravenous alteplase remains unknown in centers where bridging therapy is actively performed. The optimal dose for eventual recanalization and positive clinical outcomes in patients receiving bridging therapy also remains unknown.MethodsIn this prospective Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) sub-study, we explored the outcomes following treatment with two different doses (low- [0.6 mg/kg] or standard-dose [0.9 mg/kg]) of intravenous alteplase across 12 Korean centers where EVT is actively performed. The primary endpoint was a favorable outcome at 90 days (modified Rankin Scale scores 0 to 1). Secondary endpoints included symptomatic intracerebral hemorrhage (ICH) in all patients, and the recanalization rate and favorable outcome in patients who underwent cerebral angiography for EVT (ClinicalTrials.gov, number NCT01422616).ResultsOf 351 patients, the primary outcome occurred in 46% of patients in both the standard-(80/173) and low-dose (81/178) groups (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.72 to 1.81; P=0.582), although ICHs tended to occur more frequently in the standard-dose group (8% vs. 3%, P=0.056). Of the 67 patients who underwent cerebral angiography, there was no significant difference in favorable functional outcome between the standard- and low-dose groups (39% vs. 21%; OR, 2.39; 95% CI, 0.73 to 7.78; P=0.149).ConclusionsThere was no difference in functional outcome between the patients receiving different doses of alteplase in centers actively performing bridging therapy.

Outcome After Reperfusion Therapies in Patients With Large Baseline Diffusion-Weighted Imaging Stroke Lesions: A THRACE Trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke) Subgroup Analysis.

Stroke patients with large diffusion-weighted imaging (DWI) volumes are often excluded from reperfusion because of reckoned futility. In those with DWIvolume >70 mL, included in the THRACE trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke), we report the associations between baseline parameters and outcome. We examined 304 patients with anterior circulation stroke and pretreatment magnetic resonance imaging. Variables were extracted from the THRACE database, and DWI volumes were measured semiautomatically. Among 53 patients with DWIvolume >70 mL, 12 had favorable outcome (modified Rankin Scale score, ≤2) at 3 months; they had less coronary disease (0/12 versus 12/38; P=0.046) and less history of smoking (1/10 versus 12/31; P=0.013) than patients with modified Rankin Scale score >2. None of the 8 patients >75 years of age reached modified Rankin Scale score ≤2. Favorable outcome occurred in 12 of 37 M1-occluded patients but in 0 of 16 internal carotid-T/L-occluded patients (P=0.010). Favorable outcome was more frequent (6/13) when DWI lesion was limited to the superficial middle cerebral artery territory than when it extended to the deep middle cerebral artery territory (6/40; P=0.050). Stroke patients with DWI lesion >70 mL may benefit from reperfusion therapy, especially those with isolated M1 occlusion or ischemia restricted to the superficial middle cerebral artery territory. The benefit of treatment seems questionable for patients with carotid occlusion or lesion extending to the deep middle cerebral artery territory.

Abstract WP276: Trends in Acute Stroke Treatment Among Rural Hospitals in Minnesota: Utility of Acute Stroke Ready Hospital Designation

Background: The Minnesota Stroke System was launched in 2013 to organize and recognize hospitals able to deliver acute stroke treatment. The goal of the system is to increase access to acute stroke treatment and improve outcomes for stroke patients. The Minnesota Department of Health designates Acute Stroke Ready Hospitals (ASRHs) according to ten criteria corresponding to the 2013 Brain Attack Coalition recommendations. This analysis explores whether implementation of the Minnesota Stroke System and the corresponding adoption of standards by ASRHs corresponded to an increase in intravenous (IV) alteplase utilization among rural Minnesota hospitals between 2012 and 2017. Methods: Stroke patient care data were submitted by hospitals into the Minnesota Stroke Registry. Rural Minnesota hospitals were grouped into three categories: early adopters that became designated between 2014-2015; late adopters (designated between 2016-2017); and never-designated hospitals. Trends in IV alteplase use from 2012 to 2017 were examined in each group. Results: Among 103 rural Minnesota hospitals, 21 never received designation, 21 were designated in 2016-2017, and 61 were designated between 2014-2015. Treatment of stroke patients with IV alteplase among all rural hospitals increased in Minnesota between 2012 and 2017 from 12.9% to 15.9% (p<0.01). Among never-designated hospitals, IV alteplase use increased from 12.5% to 15.4% (p=0.13), and among late-adopting ASRHs use increased from 10.1% to 12.7% (p=0.22). In contrast, IV alteplase use significantly increased among early adopting ASRHs from 14.6% to 20.5% (p<0.0001). A significant trend was noted with IV alteplase use within the ≤3-hour window in the early adopting group (p<0.0001) and the late adopting group (p=0.02), but the trend was not significant in the never-designated group (p=0.09). Conclusions: Trends in treatment with IV alteplase was highest among early adopting ASRHs. Sustained increases in treatment rates among early adopters suggests that similar increases may be seen in late-adopting ASRHs in the future. This analysis suggests that the implementation of a statewide system of care, namely adoption of standards and hospital designation, is a driver for sustained increases in treatment rates.

Abstract TP66: IV Thrombolysis May be Safe in Patients With Lower Platelet Counts

Background & Purpose: It has been well established that intravenous alteplase (IVa) administration for treatment of acute ischemic stroke (AIS) improves clinical outcome at 3 months, and earlier treatment is more likely to result in a favorable outcome with reduced symptomatic intracranial hemorrhage (sICH). A platelet count (PC) of <100,000/mm3 remains a contraindication IVa, but the incidence is low. With the limited time to diagnose an AIS and candidacy for IVa, often lab results are received after drug initiation. Research indicates that IVa for AIS may be safe and the risk of developing sICH is low if IVa is given before PC is resulted. According to AHA/ASA guidelines, treatment is not delayed while waiting for hematologic or coagulation testing if there is no reason to suspect an abnormal test. The purpose of this study is to evaluate the incidence of asymptomatic hemorrhage (aICH), functional outcome, and safety of IVa in AIS patients with PC <100,000/mm3 prior to PC results. Methods: We retrospectively reviewed charts of patients who received IVa from January, 2009 to July, 2017 at our facility. Patients were identified and treated based on standard FDA approved guidelines. We identified patients with admission PC <100,000/mm3. We compared admission and discharge PC and NIHSS, baseline and discharge mRS, and discharge disposition. We evaluated their medical and social history and antiplatelet use prior to admission. Brain MRI and 24 hour noncontrast CT head were reviewed. Results: 511 patients received IVa for treatment of AIS at our facility during the study period. Four patients (0.97%) with a PC of <100,000/mm3 (70,000/mm3 – 97,000/mm3) received full dose IVa. None of the 4 subjects had a hemorrhagic complication on 24 hour CT. Upon discharge, all 4 patients had an improvement in the NIHSS (mean 3.7 points) and were functionally independent at discharge (mRS 0-1). All 4 patients were discharged home. Conclusion: IVa treatment in AIS with PC <100,000/mm3 did not result in aICH in this group of patients. Our study supports the claim that lower PC is rare in AIS patients and there is no need to wait for PC results before starting IVa. Full dose IVa in lower PCs may be safe, but a larger sample size should be studied to further evaluate safety.

Abstract TP37: Predictors of Hemorrhage After Endovascular Therapy: Findings From the Interrsect Study

Background: While recent endovascular therapy trials have had a minimal number of adverse events, intracerebral hemorrhage (ICH) still occurs. The predictors of ICH with endovascular therapy remain unclear. We assessed predictors of hemorrhage following endovascular thrombectomy using data from the prospectively collected, multicenter INTERRSeCT study. Methods: Patients undergoing endovascular therapy +/- intravenous alteplase (tPA) were enrolled and received baseline CT/CTA, follow-up CTA/Angiogram and 24-hr CT or MRI images. Primary outcome was any ICH as per the ECASS classification of hemorrhage. Secondary outcome was PH1/PH2 hemorrhages. We assessed the relations between ICH and baseline ASPECTS scoring, thrombus location, residual flow, collateralization, tPA use, and final recanalization state. Multivariable regression with stepwise selection was used to adjust for relevant covariates. Results: Of 242 patients who met inclusion criteria, 58 (24%) had an ICH at 24 hours (HI1 53%, HI2 19%, PH1 7%, PH2 21%). Post-procedure hemorrhage was associated with lower ASPECTS scores (p<0.001), ICA (p=0.004), proximal M1 (p=0.008), and mid-M1 (p=0.002) thrombus locations, and serum glucose (7.6 vs. 6.7; p=0.027). When adjusted for covariates, lower ASPECTS score (OR: 1.41 per point lost; 95% CI: 0.57-0.88; p=0.002), mid-M1 thrombus location (OR: 2.03; 95% CI: 1.03-4.01; p=0.041), and serum glucose (OR:1.15, 95% CI: 1.01-1.35, p=0.033) independently predicted the presence of post-procedure ICH. PH1/PH2 hemorrhages were associated with ICA thrombus (OR:2.96, 95% CI:1.05-8.33, p=0.04) after adjusting for relevant covariates. Conclusion: Early ischemia defined by imaging, mid-M1 thrombus location, and increased serum glucose are associated with increased risk of hemorrhage in patients undergoing combination tPA and endovascular therapy.

Abstract TMP19: Long Term Functional Outcome of Intravenous Alteplase Administered Over Telestroke

Background: Intravenous alteplase (rtPA) is a proven treatment for acute ischemic stroke. The implementation of telestroke networks increases access to expert stroke care and rtPA administration. Previous studies showed that faster door to needle time (DTN) leads to a better functional outcome; however DTN has been shown to be longer over telestroke when compared to that at a comprehensive stroke center. The purpose of this study is to compare the long term functional outcome of rtPA when administered at spoke hospitals through telestroke consultations to that at the comprehensive stroke center (hub). Methods: Data on baseline characteristics and long-term outcomes for all patients evaluated at the Medical University of South Carolina (MUSC) and MUSC telestroke network between January 2016 and March 2017 were collected. Eligible patients received rtPA at either the spoke or hub location during the study period. Data sources included registry data collected from telestroke consultations at 22 different spokes in South Carolina and electronic medical record data for patients at one hub. Patients who received mechanical thromectomy were excluded from the study. Functional outcome was assessed with 90 day Modified Rankin Scale (mRS). To predict the odds of a low category mRS for spoke patients compared to hub, adjusting for patient stroke severity (NIHSS), door to needle time, age, sex, and race, we estimated a logit model. T-tests and Chi-squared were used to examine the differences in continuous and categorical patient variables. Results: Total of 426 were identified (60 hub and 366 spoke patients). There were no significant differences in patient age, sex, admission NIHSS, or door to needle times between the two groups. More patients (55%) were white in the hub group compared to (61.8%) in the spoke group (P=0.02). mRS of 0-2 at 90 days was achieved in 37 (61.7%) of the hub and in 255 (69.7%) in the spoke patients (P=0.216). On logistic regression, there was no difference in the adjusted odds of having a lower mRS between spoke and hub patients (OR 1.75, p=0.104, 95% CI [0.89-3.37]). Conclusion: Our study shows no difference in the long-term functional outcome for rtPA when administered at spokes through telestroke compared to that at the hub.

Abstract 48: Which Patients With Acute Ischemic Stroke Benefit From the Lower Dosage of Intravenous Tissue Plasminogen Activator? A Cluster Data Analysis

Introduction: Although intravenous alteplase(tPA) in acute ischemic stroke(AIS) has been proved as the standard treatment, there remain concerns about increased risk of symptomatic intracranial hemorrhage. Lower dosage of tPA has been used in Japan and other Asian countries. We aim to find which AIS patients benefit from the lower dosage of intravenous tPA. Methods: We used the TIMS-CHINA database of 1440 stroke patients from 67 centers and the 4S database of 2779 patients from 11 centers. Both databases include AIS stroke patients treated with tPA, recorded with similar medical databases structures. The variables include the severity of stroke at baseline (NIHSS score), onset to needle time, dosage of tPA, symptomatic intracranial hemorrhage(sICH), modified Rankin Scale(mRS) at 3 months. We used a machine-learning method of subgroup analysis using decision trees with recursive portioning. Results: In this cluster analysis, the appropriate dosage in subsets of acute ischemic stroke patients has been explored. Based on NIHSS score to optimize the interaction effect between t-PA dosage (standard/lower), three subgroups were defined as NIHSS (1) ≤4, (2) 5-14, and (3)≥15. Their risk of sICH and benefit (as mRS0-1) are identified. The estimated difference in log odds of bleeding between standard and lower dosage is: -0.85 (p=0.15) for Group 1, 1.95 (p=0.02) for Group 2, and 0.39 (p=0.56) for Group 3, after effect adjustment of other factors and bias reduction. We are especially careful about bias reduction due to rare events: the number of bleeding cases can be small in certain subgroups. The estimated difference in log odds of efficacy between standard and lower dosage is: 0.16 (p=0.49) for Group 1, -0.16 (p=0.57) for Group 2, and -0.08 (p=0.80) for Group 3, after effect adjustment of other factors. Conclusion: Our results advocate using a lower dosage of tPA in moderate stroke, which significantly reduce the bleeding risk while achieving non-inferior performance in efficacy

Abstract TMP1: Post-Interventional Contrast Staining After Endovascular Thrombectomy Does Not Influence Clinical Prognosis

Introduction: Post-interventional contrast staining(PICS) is a common phenomenon in acute ischemic stroke (AIS) patients treated with endovascular thrombectomy(ET). Due to the small sample size in the previous studies and the limitations of image evaluation by conventional CT, determining the incidence of PICS and its consequences in AIS patients is difficult. Thus, we evaluated the incidence of PICS in AIS patients treated with ET, and its influences on functional outcome of stroke patients. Methods: 180 patients who received ET in XuanWu Hospital were analyzed retrospectively. All patients were examined by dual-energy CT (DECT) but not conventional CT within 24 h after ET. The primary outcome was the incidence of PICS. The second outcome was symptomatic ICH (sICH) according to the ECASS-III definition, as well as functional outcome assessed by modified Ranks scale (mRS), with mRS scores 0-1 indicating no disability, mRS scores 0-2 indicating functional independence and mRS scores 6 indicating death. Results: 50 of 180 patients (27.8%) had PICS in post-treatment DECT scans. We first used basic statistic analyses, showing that PICS decreased the percentage of favorable clinical prognosis in anterior circulation stroke at both 3-month (P<0.05 for mRS scores at 0-1 and 0-2) and long-term follow up of 12 (3-26.5) months (P<0.05 for mRS scores at 0-1 and 0-2). An increase in the risk of both total ICH/sICH (P<0.001) and mortality (P<0.05) in posterior circulation stroke at 3-month follow up. However, the logistic regression analyses further revealed that PICS only increased total (P<0.01) but not sICH risk. Furthermore, the logistic regression analyses did not show statistical difference in good clinical outcomes or mortality between the two groups. In the logistic regression analyses, we adjusted relative confusing factors, including age, baseline NIHSS, hypertension, DM, AF, etiology of stroke, time from onset to groin puncture, ASPECT score, pretreatment with antiplatelet or anticoagulation drugs, additional intra-arterial thrombolysis, intravenous alteplase, location of occluded arteries, sICH, and TICI scores for clinical outcomes and/or sICH. Conclusion: PICS was common in AIS patients with ET, but it did not affect functional outcome and sICH.

Abstract TP305: Geographical Dispersion of Patients Referred to a Comprehensive Stroke Center in a Rural Setting

Introduction: Most patients with stroke in Iowa are initially seen in small community hospitals and are subsequently transferred to another institution with a higher level of care. The Iowa Stroke Registry (ISR) was developed to assess the system of stroke care in the state. Community hospitals in the state are supported by the comprehensive stroke center (CSC) through consultation for acute stroke treatment. The objective for this project was to analyze the geographical dispersion of transfers to the CSC to begin an evaluation of the system of stroke care in the state. Method: We analyzed the prospectively collected data in the Iowa Stroke Registry (ISR). The ISR has collected data from 32 hospitals: comprehensive (1), primary (15), and stroke capable hospitals in Iowa beginning in 2010. To date over 23, 000 patients have been enrolled. Information from this analysis included the CSC data only collected in a national database and imported ino the ISR from 2015-April, 2017 that included zip code data. During that time period 2576 patients were direct admissions or transfers to the CSC. Distances were based on the number of miles between the patients’ and CSC zip code. Results: Approximately 80% of all stroke patients at the CSC were transferred from a community hospital. Patients originated in 78 of the 99 counties in Iowa. The median distance was 63 miles. Of the transfers from local hospitals, 86% were within 90 miles with the largest group 60-89 miles from the CSC. Of all patients transferred for ischemic stroke approximately 30% received treatment with intravenous alteplase at the outside hospital. Conclusion: In conclusion, these data suggest a high degree of geographical dispersion for stroke patients transferred to a CSC in a rural state. This analysis of the system of stroke care in Iowa indicates the CSC provided support to multiple community hospitals for acute stroke treatment. Further analysis of the system of stroke care is needed to better understand patient transfers including mode of transfer and reason for transfer.

Abstract TP34: Real World Efficacy of Endovascular Thrombectomy in Patients With Acute Cerebral Large Vessel Occlusion in Japan - First Report From RESCUE-Japan Registry 2

Introduction: Several randomized trials showed the endovascular thrombectomy (EVT) was effective in patients with acute cerebral large vessel occlusion, but the efficacy to general patients were unknown. Methods: Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism (RESCUE)-Japan Registry 2 was prospective registry of acute cerebral large vessel occlusion at centers in Japan. The patients were 20 years or elder and admitted within 24 hours after the onset of cerebral large vessel occlusion in both anterior and posterior circulation. Primary endpoint was good outcome defined by modified Rankin Scale (mRS) of 0-2 at 90 days after onset. Secondary endpoint was mortality. Adjusted odds ratio (OR) was estimated by logistic regression model accounted for potential confounders. Safety endpoints were all bleeding included intracerebral hemorrhage, gastrointestinal bleedings, recurrence of stroke, and other adverse events within 90 days. Results: Consecutive 2420 patients were recruited from October 2014 to September 2016, and follow-up ended at January 2017. Excluding 12 patients who did not meet inclusion criteria, 1281 patients were treated with EVT and 1127 were without. Mean age was 75 and 77 years in EVT and no-EVT groups, respectively. Posterior circulation accounted for 13% in both groups. Intravenous alteplase was administered in 47% and 32% of EVT and no-EVT groups, respectively. Good outcome was observed in 41.7% and 30.7% the EVT group and no-EVT group, respectively (p<0.0001). Adjusted OR of good outcome of EVT relative to no-EVT was 1.79 (95%CI: 1.39-2.29). Prespecified subgroup analyses showed the EVT was effective in anterior circulation [adjusted OR 1.7 (95%CI 1.3-2.2)] while not effective in posterior circulation [adjusted OR 1.3. (95%CI 0.6-3.0)] (interaction p=0.34). The mortality was 8.8% and 13.6% in EVT group and no-EVT group (p=0.0002). Intracerebral bleeding occurred within 72 hours from onset in 26% in EVT group while 19% in no-EVT group (p<0.0001). Conclusions: EVT was shown effective in general patients with acute cerebral large vessel occlusion in terms of mRS and mortality at 90 days. The indication of EVT for posterior circulation should be reconsidered. <!--EndFragment-->

Abstract WP240: Regional Disparities in Stroke Transfers for Endovascular Treatment- Outcomes from the Early Years of Neurointervention

Introduction: Acute stroke care has been revolutionized with the advent of intravenous alteplase and endovascular therapy. The number of centers in the United States equipped to offer endovascular therapy are limited, often necessitating inter-hospital transfer. We studied the outcomes of such patients in terms of mortality and disability, and attempted to determine the possible contributory factors in the early years of neurointervention for acute stroke management. Methods: We used the Nationwide Inpatient Sample data to identify the acute stroke patients requiring transfer for endovascular treatment, the National Center for Health Statistics data to determine their location, the United States Census Bureau website for determining the population demographics, the Joint Commission data on the distribution of Primary Advanced and Comprehensive Stroke Centers, and the Human Resources and Services Administration data on delivery of medical care. We compared the outcomes in the four major regions of the country in terms of mortality and disability at discharge. Results: Age above 80 years (p<0.05) and a high Charlson’s co-morbidity index (p<0.01) were consistent predictors for increased disability in transferred patients receiving endovascular therapy. Age greater than 80 years was also a predictor for higher mortality (p<0.001) in all regions. The prevalence of significant disability was higher in the Midwest compared to the national average (p=0.0147). Conclusion: Distribution of healthcare facilities capable of offering endovascular treatments affects time to treatment and consequently, outcomes. Strategic triage system and distribution of Primary Advanced and Comprehensive Stroke Centers could help reduce disparities of outcomes.

Abstract WP65: Higher Glucose Level Associated With Unfavorable Outcome in Acute Minor Ischemic Stroke After Thrombolytic Therapy

Introduction: In real world practice, patients with minor stroke symptoms are still treated with thrombolytic therapy and majority of them recover with favorable outcomes at 90 days, but there is room to identify avenues to further enhance their outcomes. We aimed to investigate the risk factors associated with the unfavorable outcome at 90 days after thrombolysis for acute minor ischemic stroke (AMIS). Methods: 152 consecutive patients presented with AMIS (NIHSS ≤3) and received intravenous alteplase between December 2012 and February 2017. Baseline clinic-demographic, characteristics and laboratory tests were recorded. Unfavorable outcome was defined as modified Rankin Scale (mRS) of 2-6 at 90 days. Univariate analysis followed by multivariate analysis was used to identify risk factors for unfavorable outcome. A receiver operating characteristic curve was used to evaluate the predictive value. Results: 113 out of 152 patients (74%) were included in the final analysis, age 59 (53-67), 72.6% men. 32 patients (28.3%) experienced unfavorable outcomes. After adjusting for covariates, only serum glucose level on admission remained an independent factor for unfavorable outcome (OR 1.43, 95% CI: 1.10-2.72, p =0.014), with a 0.617 predictive value for the unfavorable outcome. Conclusions: About 28% of patients with AMIS in this cohort had an unfavorable outcome at 3 months after thrombolysis. Addressing higher serum glucose level on admission may be a viable therapeutic strategy to improve prognoses in these patients.

Abstract 160: Outcomes and Relationship to Time: Alteplase Administration in Patients With Large Vessel Occlusion in Non-intervention Group of the Hermes Collaboration

Background: Data on outcomes and time effects of intravenous alteplase on outcome of patients with documented large vessel occlusion (LVO) are scarce. Aim: To define the effect of onset to treatment time (OTT) on functional outcomes and mortality among patients in the non-interventional arm of endovascular stroke trials. Methods: Individual patient-level data from the HERMES collaboration were pooled from seven trials that randomized patients with proven LVO to mechanical thrombectomy + best medical therapy vs. best medical therapy alone. In this analysis only patients who received alteplase directly at the endovascular hospital were included. Primary outcome was degree of disability (mRS distribution) at 3 months. Secondary outcomes included functional independence (mRS 0-2) at 3 months, mortality by 3 months, and symptomatic intracranial hemorrhage (sICH). Results: Among 893 patients in the control arms, 601 received alteplase at the endovascular hospital. The mean age was 66.0 years (SD 13.9), 50% were women, and median NIHSS was 17. 82% were treated within 3 hours from onset and 17% between 3 and 4.5 hours. SICH was observed in 20/585 (3.4%), 3.5% with OTT within 3h vs 3.2% with OTT 3-4.5 hours, p = 1.00. For each 60-minute delay in therapy the cOR for improvement on the mRS was 0.80 (95% CI 0.68 to 0.95, p=0.01) (Figure-A). For each 60-minute delay, the OR for functional independence (mRS 0-2) was 0.82 (95%CI, 0.66 to 1.03, Figure-B). There was no time effect on mortality (cOR, 0.99 (95%CI, 0.79 to 1.23). The reduction in treatment effect by time was not modified by age, baseline NIHSS score, baseline ASPECTS score or occlusion location (p interaction =0.21, 0.81, 0.88, 0.67 respectively). Conclusion: Faster intravenous thrombolysis delivery is associated with better functional recovery in patients with LVO not destined to receive mechanical thrombectomy. Figure legend: A: 90-day functional outcomes stratified by OTT. B: Proportion of mRS 0-2 the 90-day against OTT

Abstract TP321: Effect of Very Early Mobilization After IV Alteplase on 90 Day Functional Outcome

Purpose: To determine if very early mobilization impacts outcomes at 90 days for ischemic stroke patients receiving intravenous alteplase (tPA). Background: Early mobilization of critical care patients improves outcome, length of stay, and patient satisfaction. Outcomes data of very early mobilization for stroke patients have been mixed, and data for patients mobilized within 24 hours of receiving tPA is limited. We have presented safety data for a nursing-driven early mobility protocol for stroke patients. Methods: Medical records of ischemic stroke patients who received tPA between 2012 and 2016 at two urban hospitals were reviewed for timing of earliest mobilization following tPA treatment. Patients who received endovascular treatment, were placed on comfort care day zero or one, were mobilized after the first 24 hours, transferred out or left against medical advice, or for whom there was no 90 day modified Rankin Scale (mRS) reported were excluded from the analysis. Multinomial regression was used to determine if the time first mobilized to highest safe level within 24 hours after tPA treatment impacted mRS at 90 days, adjusting for patients’ disability status prior to stroke, stroke severity using National Institutes of Health Stroke Scale (NIHSS), and age. Results: Of 193 patients included in the final analysis, 43.0% (n=83) were female, mean age was 70.6 (±13.0), and the median admit NIHSS was 6.0 [Interquartile range (IQR): 3.0, 11.0]. The median time first mobilized after tPA was 9.0 hours [IQR: 5.0, 16.0]. At 90 days, 31.6% (n=61) of patients reported no symptoms (mRS 0), 35.2% (n=68) some symptoms or slight disability (mRS 1-2), 19.2% (37) moderate to severe disability (mRS 3-5), and 14.0% (n=27) had expired (mRS 6). There was no relationship between mobilizing earlier and likelihood of moderate or severe disability (Adjusted Odds Ratio (AOR) = 1.05 per hour increase in mobilization; p=0.183) or death (AOR=1.06 per hour increase in mobilization; p=0.143) compared to no symptoms at 90 days. Conclusions: This study showed that earlier mobilization within 24 hours after tPA did not worsen functional outcome based on 90 day mRS. Our data support very early mobilization to their highest safe level of stroke patients receiving tPA.