Use Of Tissue Plasminogen Activator Research Articles

Risk factors and outcomes of intravenous tissue plasminogen activator and endovascular thrombectomy utilization amongst pediatrics acute ischemic stroke.

Pediatric stroke is a debilitating disease. There are several risk factors predisposing children to this life-threatening disease. Although, published literature estimates a relatively high incidence of pediatric stroke, treatment guidelines on intravenous tissue plasminogen activator and endovascular thrombectomy utilization remain a dilemma. There is a lack of large population-based studies and clinical trials evaluating the efficacy and safety outcomes associated with these treatments in this unique population. We sought to determine the prevalence of risk factors, concurrent utilization of intravenous tissue plasminogen activator and endovascular thrombectomy, and associated outcomes in pediatric stroke hospitalizations. We performed a retrospective analysis of the Nationwide Inpatient Sample data (2003-2014) in pediatric (1-21 years of age) acute ischemic stroke hospitalizations using ICD-9-CM codes. The multivariable survey logistic regression model was weighted to account for sampling strategy, evaluate predictors of hemorrhagic conversion, and treatment outcomes (mortality, morbidity, and discharge disposition) amongst pediatric stroke hospitalizations. In this analysis, 9109 patients between 1 and 21 years of age were admitted during 2003-2014 for acute ischemic stroke. Of these 9109 patients, 119 (1.30%) received endovascular thrombectomy alone, 256 (2.82%) intravenous recombinant tissue plasminogen activator, and 69 (0.75%) both endovascular thrombectomy and intravenous recombinant tissue plasminogen activator. We found overall high prevalence of conditions like epilepsy (19.59%), atrial septal defect (11.76%), sickle cell disease (8.63%), and moyamoya disease (5.41%) in pediatric acute ischemic stroke patients. Unadjusted analysis showed high prevalence of all-cause in-hospital mortality in combined endovascular thrombectomy and intravenous recombinant tissue plasminogen activator utilization group, and higher prevalence of hemorrhagic conversion and morbidity in endovascular thrombectomy utilization group compared to other groups (p < 0.0001). Multivariate adjusted analysis showed that children with endovascular thrombectomy utilization (aOR: 19.19; 95% CI: 2.50-147.29, p = 0.005), intravenous recombinant tissue plasminogen activator utilization (aOR: 8.85; 95% CI: 1.92-40.76, p = 0.005), and both (endovascular thrombectomy and intravenous recombinant tissue plasminogen activator) utilization (aOR: 7.55; 95% CI: 1.16-49.31, p = 0.035) had higher odds of hemorrhagic conversion compared to no-treatment group. We found various risk factors associated with pediatric stroke. The early identification can be useful to formulate preventive strategies and influence the incidence of pediatric stroke. Our study results showed that use of intravenous recombinant tissue plasminogen activator and endovascular thrombectomy increase risk of mortality and hemorrhagic conversion, but we suggest to have more clinical studies to evaluate the idea candidates for utilization of intravenous recombinant tissue plasminogen activator and endovascular thrombectomy based on risk: benefit ratio.

Abstract TP10: Intra-Arterial Thrombolysis After Failed Mechanical Thrombectomy: A STRATIS Registry Subgroup Analysis

Background: Limited prospective data exists on the use of intra-arterial (IA) thrombolytics as rescue therapy(RT) after failed mechanical thrombectomy(MT) in acute ischemic stroke(AIS) patients with large vessel occlusions LVO). The aim of this study is to investigate the use of IA recombinant tissue plasminogen activator(IA-rtPA) as RT in the prospective STRATIS Registry. Methods: Data from the STRATIS Registry, a multicenter study of AIS patients treated with the Solitaire stent-retriever as the first choice therapy within 8 hours from symptoms onset, were analyzed. Clinical and angiographic outcomes were compared between patients treated with and without IA-rtPA. Both anterior and posterior circulation occlusions were included in this substudy. Results: Of the 938 STRATIS patients with IA-tPA use reported, 809 and 129 were in the no IA-rtPA(83.2%) and IA-rtPA(13.8%)groups, respectively. No difference was seen in baseline demographics. Site of occlusion was similar between the groups, with the majority occurring in the MCA(72.4% versus 73.6%, p=0.74). IV-rtPA was administered in 63.0% and 70.5% of no IA-rtPA and IA-rtPA patients(p=0.11). Median IA-rtPA dose was 4mg(IQR 2-12). Mean onset to arterial puncture time was shorter in the IA-rtPA group(200.2±104.6 versus 228.2±98.5 minutes, p=0.003); however, mean puncture to procedure end time was longer in the IA-rtPA group(78.7±43.1 versus 63.1±35.9 minutes). Mean number of passes (2.2±1.4 versus 1.8±1.2,p=0.001) and rate of distal embolization(67.8% versus 54.5%, p=0.007) was significantly higher in the IA-rtPA group. Core lab adjudicated substantial reperfusion (mTICI≥2b) was achieved in 88.4% and 84.7% of no IA-rtPA and IA-rtPA patients(p=0.16). No difference was observed in rates of symptomatic intracranial hemorrhage(sICH) (1.4% versus 1.6%,p=0.70), good functional outcome (mRS≥2, 57.3% versus 59.2%, p=0.86), or mortality (15.5% versus 13.3%,p=0.80) at 90-days. Conclusion: Use of IA-rtPA after failed thrombectomy was not associated with an increased risk of sICH or mortality in the STRATIS Registry. These results suggest that IA thrombolysis may be a safe option as rescue therapy in select patients.

Time to Wake-Up: Extending the Window for Management of Unknown-Onset Strokes.

The term "Wake-Up Stroke" is applied to a patient who displays no symptoms before sleep, but wakes with neurologic deficits suggestive of stroke. The current guidelines for acute ischemic stroke limit intravenous tissue plasminogen activator use to stroke patients in whom symptom onset or last known well is less than 4.5 hours. Approximately one-third of acute ischemic stroke patients present with unknown time of symptom onset and are often not eligible for intravenous reperfusion therapy in clinical practice. This review provides an overview of several earlier trials that used advanced neuroimaging to determine eligibility for reperfusion therapy in patients with unknown stroke onset. The reassuring results of these earlier trials that led to recent thrombolysis trials specifically targeted at "wake-up stroke" patients are discussed in this review. Ongoing studies aim to expand our knowledge regarding the safety and efficacy of thrombolysis in these patients.

In-hospital Ischemic Stroke Treated by Mechanical Thrombectomy.

We investigated in-hospital stroke (IHS) treated by mechanical thrombectomy in comparison with out-of-hospital stroke (OHS) to clarify the points of concern in IHS at our institution. Between September 2015 and June 2018, 19 patients with IHS who underwent mechanical thrombectomy (IHS group) were enrolled, and compared with 154 patients with OHS (OHS group) regarding patient characteristics, technical results, and outcome. In this study, we set the detection time in the IHS group as patient arrival time, termed "Door" in the OHS group. Cardiology and gastroenterology were the two main admitting departments, including four (21%) patients of IHS group. In all, 15 (79%) patients had atrial fibrillation; however, less than one-third of them was taking anticoagulant drugs at onset. There were only two cases of direct consultation to the stroke specialists, although IHS onset was mainly recognized by nurses. The median age in the IHS group was 81 (interquartile range (IQR), 76-86.5) versus 80 in the OHS group (IQR, 73-85; p = 0.43), and the median initial National Institutes of Health Stroke Scale score was 21 (IQR, 16-23) versus 21 (IQR, 14-26; p = 0.92), respectively. Sex, Alberta Stroke Program Early CT Score, etiology, and occlusion site did not differ between groups. The rate of use of intravenous tissue plasminogen activator (IV-tPA) was 26% in the IHS group versus 49% in the OHS group (p = 0.065). The median time of detection to imaging, detection to needle for IV-tPA, and detection to puncture were 32, 69, and 87 minutes, respectively, in the IHS group, being significantly longer than those in the OHS group (11, 30, and 50 minutes; p <0.01, p <0.01, and p <0.01, respectively). The median time of puncture to reperfusion was 39 minutes, being significantly shorter than that in the OHS group (82 minutes; p <0.01). Successful reperfusion defined as thrombolysis in cerebral infarction (TICI) 2b-3 was obtained in 94.7% of the IHS group versus 83.1% of the OHS group (p = 0.19). A favorable outcome (modified Rankin Scale score 0-2) at 90 days was achieved by 36.8% (IHS) versus 35.1% (OHS) of patients (p = 0.88). The rate of symptomatic procedural complications was 0% (IHS) versus 7.1% (OHS; p = 0.23). The rate of death at 90 days was 15.8% (IHS) versus 12.3% (OHS; p = 0.67). The times of detection to imaging and of detection to puncture in the IHS group were longer than those in the OHS group; however, patients in the IHS group had shorter reperfusion. The outcome of the IHS group did not differ from that of OHS group. Our study suggests that the time course of treatment should be improved and rapid stroke pathways involved in consultation with the stroke specialists for IHS should be organized.

Qualitative Posttreatment Diffusion-Weighted Imaging as a Predictor of 90-day Outcome in Stroke Intervention.

The aim was to assess the ability of post-treatment diffusion-weighted imaging (DWI) to predict 90-day functional outcome in patients with endovascular therapy (EVT) for large vessel occlusion in acute ischemic stroke (AIS). We examined a retrospective cohort from March 2016 to January 2018, of consecutive patients with AIS who received EVT. Planimetric DWI was obtained and infarct volume calculated. Four blinded readers were asked to predict modified Rankin Score (mRS) at 90 days post-thrombectomy. Fifty-one patients received endovascular treatment (mean age 65.1 years, median National Institutes of Health Stroke Scale (NIHSS) 18). Mean infarct volume was 43.7 mL. The baseline NIHSS, 24-hour NIHSS, and the DWI volume were lower for the mRS 0-2 group. Also, the thrombolysis in cerebral infarction (TICI) 2b/3 rate was higher in the mRS 0-2 group. No differences were found in terms of the occlusion level, reperfusion technique, or recombinant tissue plasminogen activator use. There was a significant association noted between average infarct volume and mRS at 90 days. On multivariable analysis, higher infarct volume was significantly associated with 90-day mRS 3-5 when adjusted to TICI scores and occlusion location (OR 1.01; CI 95% 1.001-1.03; p = 0.008). Area under curve analysis showed poor performance of DWI volume reader ability to qualitatively predict 90-day mRS. The subjective impression of DWI as a predictor of clinical outcome is poorly correlated when controlling for premorbid status and other confounders. Qualitative DWI by experienced readers both overestimated the severity of stroke for patients who achieved good recovery and underestimated the mRS for poor outcome patients. Infarct core quantitation was reliable.

TPA Use for Central Line De-Occlusion and Its Relationship to Symptomatic Venous Thromboembolism in Pediatric Leukemia Patients

Introduction: Venous thromboembolism (VTE) is a known complication of pediatric leukemia with reported incidence ranging widely from 1.5-40%. It is associated with significant morbidity including loss of venous access, post thrombotic syndrome, and thrombosis recurrence or embolization. Increased risk of VTE in these patients is often multifactorial. There are currently no standard guidelines for VTE prophylaxis in pediatric leukemia patients, and it is unclear which patients are at highest risk. Identifying potential markers for patients at risk for VTE could be helpful for guiding prophylaxis practices and ultimately decreasing rates of VTE in these children. Thrombolytic agents are commonly used to treat catheter obstruction by breaking down fibrin that forms within the catheter. Therefore, we hypothesize that patients requiring more tissue plasminogen activator (TPA) for treatment of catheter obstruction may be at higher risk of developing fulminant thromboses. Therefore, the primary objectiveof this study is to determine the association between central line clearance with TPA and development of symptomatic VTE (sVTE) in pediatric leukemia patients. Methods: This is a multi-center,retrospective cohort study of patients under 21 years old with a central line (CVC), including peripherally inserted central catheters (PICC), who began treatment at Weill Cornell Medicine (WCM) or Memorial Sloan Kettering Cancer Center (MSKCC) from January 2012-December 2015 for newly diagnosed or relapsed leukemia. Patients were excluded if they had a prior VTE, or an incidental VTE was identified. Transplant and CAR-T -cell patients were excluded, as were those who transferred into the institution over 30 days from start of treatment. Data collected included demographics, disease-specific information (including type of leukemia, treatment regimen, and CVC details), dates of TPA administration, and details of sVTE. Data analysis was performed with Fisher's exact test andWilcoxon rank-sum test. Results: A total of 96 patients with leukemia were included. The median age was 6.5 years (Q1, Q3: 3.15-15.05 years), and 55% (n=53) were male. 78% (n=75) were new diagnoses. Acute lymphoblastic leukemia (ALL; 72%, n=69) was most common, followed by acute myelogenous leukemia (AML; 25%, n=24), and mixed lineage leukemias (3%, n=3). There were no significant differences between gender, age, type of leukemia, or TPA use between the two centers. The overall incidence of sVTE over the 4-year period in this cohort was 6% (6/96). At the time of thrombosis, five of the six patients had a PICC line in place and one patient had a mediport (Table 1). Four sVTE patients were diagnosed with ALL. Four of the thromboses were line-associated, one was a sinus venous thrombosis, and one was an inferior vena cava thrombus. Five of the six sVTEs were diagnosed at WCM. There was no association found between use of TPA for line de-occlusion and development of sVTE (OR 0.55, CI 0.07-6.57, p=0.61) or between number of TPA doses needed and development of sVTE (p=0.830). The patients who developed sVTE were significantly older than those who did not develop sVTE (Figure 1, p=0.048). There was no significant difference between gender and development of sVTE. A significant difference (p &lt;0.05) was seen when analyzing the association between PICC line and development of sVTE, however the sample size was too small to draw formal conclusions. Conclusions: In our cohort, neither TPA use for line occlusion nor the number of TPA doses was predictive of sVTE development. This may be due to the small sample size and low number of sVTE events. Single center analysis of data from WCM, however, previously indicated a significant association between TPA use and development of thrombosis in their patients. Given the increased use of PICC lines at WCM, this raises the question of whether TPA use may be predictive in patients who have PICC lines. Our data are consistent with previous pediatric studies, which found older age to be a risk factor for thrombosis. Analysis of a larger cohort of patients is necessary to further investigate our hypothesis. Given the importance of preventing sVTE in pediatric leukemia patients, further prospective studies are needed to investigate potential predictors of thrombosis in this population. Disclosures Cooley: off-label: Other: drug use.

Ischemic stroke and mitochondria: mechanisms and targets.

Stroke is one of the main causes of mortality and disability in most countries of the world. The only way of managing patients with ischemic stroke is the use of intravenous tissue plasminogen activator and endovascular thrombectomy. However, very few patients receive these treatments as the therapeutic time window is narrow after an ischemic stroke. The paucity of stroke management approaches can only be addressed by identifying new possible therapeutic targets. Mitochondria have been a rare target in the clinical management of stroke. Previous studies have only investigated the bioenergetics and apoptotic roles of this organelle; however, the mitochondrion is now considered as a key organelle that participates in many cellular and molecular functions. This review discusses the mitochondrial mechanisms in cerebral ischemia such as its role in reactive oxygen species (ROS) generation, apoptosis, and electron transport chain dysfunction. Understanding the mechanisms of mitochondria in neural cell death during ischemic stroke might help to design new therapeutic targets for ischemic stroke as well as other neurological diseases.

TISSUE PLASMINOGEN ACTIVATOR IN CARDIAC ARREST SECONDARY TO MASSIVE PULMONARY EMBOLUS

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Cardiac arrest secondary to massive pulmonary embolism carries a poor prognosis. In most cases, the diagnosis is made post-mortem. CASE PRESENTATION: 64-year-old lady with past medical history of DVT and pulmonary embolus (PE) not on anticoagulation, type 2 diabetes, hypertension, coronary artery disease presented with sudden onset shortness of breath and mild chest pain of less than 1 day duration. Upon presentation, she was hypotensive, tachycardic, and tachypneic. Initial EKG showed ST-elevation in leads 3 and V1 with deep S wave in lead 1. CTA chest showed extensive bilateral pulmonary emboli and RV to LV ratio greater than 2. Shortly after returning from CT, she became hypoxia and bradycardia followed by asystole. CPR was started and she attained ROSC after 1 cycle of CPR. She was given 50 mg IV tPA bolus followed by continuous infusion of 50 mg over 1 hour. Blood pressure improved after administration of tPA and she was intubated thereafter for airway protection. She had cardiac arrest again after intubation and attained ROSC after 1 cycle of CPR. She was transferred to the ICU and started on heparin drip and vasopressors. Her condition continued to improve and she was extubated the next day. She was ultimately discharged in stable condition on direct-acting oral anticoagulant. DISCUSSION: The diagnosis of PE during an in-hospital cardiac arrest can be difficult. In most cases, thrombolytic therapy is given based on high clinical suspicion, often due to the presence of echocardiogram changes on point-of-care ultrasound. “McConnell sign,” which is a specific pattern of RV dysfunction is observed in massive PE and is characterized by akinesis of the mid free wall and normal contractility of the apical wall. It is approximately 77% sensitive and 94% specific [3]. However in clinical practice, McConnell sign can be difficult to recognize. tPA may also be underutilized due to concern for major bleeding. However, there is literature to suggest that administration of tPA during cardiac arrest is not associated with increased risk of bleeding and often leads to decreased time to return of spontaneous circulation [1]. The optimal timing of tPA administration has yet to be determined. In retrospective studies, tPA is either given as a single 50 mg bolus, 50 mg bolus followed by a second 50 mg bolus, or as 50 mg bolus followed by 85 mg over 90 minutes [2]. However, there are no trials that compare the utility and efficacy of these protocols against each other. CONCLUSIONS: There is general consensus that tPA should be administered during cardiac arrest in patients with high suspicion of PE, however the optimal dose and timing of tPA administration is yet to be determined. In our patient, a dose of 50mg IV bolus followed by 50mg infusion over 1 hour had resulted in a favorable outcome. Reference #1: Yousuf T, Brinton T, Ahmed K, et al. Tissue Plasminogen Activator Use in Cardiac Arrest Secondary to Fulminant Pulmonary Embolism. J Clin Med Res. 2016;8(3):190-5. Reference #2: Kürkciyan I, Meron G, Sterz F, et al. Pulmonary embolism as a cause of cardiac arrest: presentation and outcome. Arch Intern Med. 2000;160(10):1529-1535. Reference #3: Borloz, Matthew P., William J. Frohna, Carolyn A. Phillips, and Michael S. Antonis. "Emergency Department Focused Bedside Echocardiography In Massive Pulmonary Embolism.” The Journal of Emergency Medicine 41, no. 6 (2011): 658-60. https://doi.org/10.1016/j.jemermed.2011.05.044. DISCLOSURES: No relevant relationships by basma al-bast, source=Web Response No relevant relationships by Mirza Ali, source=Web Response No relevant relationships by Abdisamad Ibrahim, source=Web Response No relevant relationships by Thamer Sartawi, source=Web Response No relevant relationships by Tareq Zaza, source=Web Response

T53

The simultaneous occurrence of acute ST-segment elevation myocardial infarction and acute ischemic stroke is an uncommon and complex clinical presentation. Although the medical treatment of both diseases is similar, data regarding optimal reperfusion therapy are limited. Nevertheless, use of tissue plasminogen activator may be a reasonable strategy for treatment of both diseases. We present a rare case of coexisting thrombosis of the coronary artery and mid cerebral artery that was managed successfully with tissue plasminogen activator thrombolytic therapy.

Direct Oral Anticoagulant Plasma Levels for the Management of Acute Ischemic Stroke

Introduction: The management of acute ischemic stroke in patients on direct oral anticoagulants (DOACs) is challenging. However, the substance-specific plasma level could guide treatment decisions on recanalization therapies. We present a plasma-level-based protocol for emergency treatment of stroke patients on oral anticoagulants. Bleeding complications and clinical outcome for patients on DOACs are reported and compared to patients on vitamin K antagonists (VKAs). Methods: In patients with acute ischemic stroke and suspected use of DOACs within 48 h prior to hospital admission, plasma levels were measured using the calibrated Xa-activity (apixaban, edoxaban, rivaroxaban) or the Hemoclot®-assay (dabigatran). Levels <50 ng/mL were supportive for thrombolysis, while high values >100 ng/mL excluded patients from recombinant tissue plasminogen activator use. For patients on VKAs, the cutoff was set at international normalized ratio of 1.7. Endovascular thrombectomy of a large vessel occlusion was performed independently from coagulation testing. Consecutive patients were included in an observational registry. Results: Five hundred and twenty-two patients (261 on VKAs and 261 on DOACs) were included. Thirty patients (11.5%) on VKAs and 24 (9.2%) on DOACs received thrombolysis, followed by mechanical thrombectomy in 10 and 14 patients, respectively. Seventeen patients in each group received thrombectomy only. Symptomatic intracranial hemorrhage associated with thrombolysis occurred in 1 patient on VKA (3.3%) and 1 on DOAC (4.2%; p = 0.872). The turnaround time of specific assays did not show a significant delay in comparison to standard coagulation parameters. Conclusion: DOAC plasma levels could support decisions on emergency treatment of ischemic stroke. Systemic thrombolysis below suggested thresholds appears preliminary feasible and safe without an excess in bleeding complications.

Using Intra-arterial tPA for Severe Frostbite Cases. An Observational Comparative Retrospective Study.

Frostbite causes tissue damage through five major mechanisms, out of which two are amenable to treatment. The first-line treatment is rapid rewarming therapy using water at 40°C to 42°C, which addresses the formation of ice crystals in the intra and extra cellular compartments. The second mechanism is progressive tissue ischemia after rewarming and is only accessible to a second-line therapy represented by thrombolysis. This study aimed to determine the efficacy of thrombolysis. This is a single-center retrospective cohort study, where it was aimed to evaluate two groups of patients. A total of 18 patients were included in this study. Mean times between injury to thrombolytic therapy and admission to thrombolytic therapy was 26.04 hours (SD 13.6) and 9.65 hours (SD 9.89), respectively. All patients suffered injuries ranging from second-degree deep to third degree. The rate of patients having complete, partial, and no angiographic responses were 55.6%, 11.1%, and 33.3%, respectively. The main outcome of interest showed that 11 (61.1%) patients in total had amputations at different levels. Results showed that in the intervention group, five (55.6%) of the patients had amputations compared with six (66.7%) from the control group (P = .6) at comparable levels of amputation. The literature supports that the use of intra-arterial tissue plasminogen activator might be beneficial for severe cases of frostbites; however, it lacks of studies of major significance and results are often controversial. Our study has not shown statistically significant results on amputation levels and cannot support the hypothesis of efficacy of thrombolytic therapy.

Calcitriol protects the Blood-Brain Barrier integrity against ischemic stroke and reduces vasogenic brain edema via antioxidant and antiapoptotic actions in rats

BackgroundVasogenic brain edema is the most important complication of ischemic stroke that aggravates primary brain injury. Ischemia-Reperfusion (IR)-induced Blood-Brain Barrier (BBB) impairment limits the use of recombinant tissue plasminogen activator (r-tPA) by increasing the possibility of hemorrhagic transformation and contributing to vasogenic edema and neuroinflammation. This study examined the effects of post-ischemic treatment with calcitriol on cerebral infarction, vasogenic edema formation and BBB disruption in a rat model of ischemic stroke. MethodsMale Sprague-Dawley rats were divided into three main groups, including the sham, IR + vehicle and IR + calcitriol groups. Transient focal cerebral ischemia was induced by a 60-min-long occlusion of the left middle cerebral artery. The infarct volume, brain edema, BBB permeability and antioxidant enzyme activities were evaluated 24 h after ischemia. Immunohistochemical analysis was conducted to investigate cell apoptosis and Brain-Derived Neurotrophic Factor (BDNF) protein expression five days after ischemia. ResultsCompared to the IR + vehicle group, the IR + calcitriol group showed a reduced brain infarction volume, attenuated brain edema formation and improved BBB function. These protective effects were followed by the upregulation of antioxidant enzyme activities in the brain tissue. Additionally, a diminished cell apoptosis and an increased BDNF immunoreactivity were obtained in the IR + calcitriol group. ConclusionCalcitriol may reduce brain injury and attenuate vasogenic edema by upregulating antioxidant enzymes activities, reducing cell apoptosis and increasing BDNF protein in the brain tissue in a rat model of ischemic stroke.

57-Year-Old Man With Vertigo

57-Year-Old Man With Vertigo

Cost-effectiveness of intrapleural use of tissue plasminogen activator and DNase in pleural infection: evidence from the MIST2 randomised controlled trial.

The MIST2 (Second Multicentre Intrapleural Sepsis Trial) trial showed that combined intrapleural use of tissue plasminogen activator (t-PA) and recombinant human DNase was effective when compared with single agents or placebo. However, the treatment costs are significant and overall cost-effectiveness of combined therapy remains unclear.An economic evaluation of the MIST2 trial was performed to assess the cost-effectiveness of combined therapy. Costs included were those related to study medications, initial hospital stay and subsequent hospitalisations. Outcomes were measured in terms of life-years gained. All costs were reported in euro and in 2016 prices.Mean annual costs were lowest in the t-PA-DNase group (EUR 10 605 for t-PA, EUR 17 856 for DNase, EUR 13 483 for placebo and EUR 7248 for t-PA-DNase; p=0.209). Mean 1-year life expectancy was 0.988 for t-PA, 0.923 for DNase, and 0.969 for both placebo and t-PA-DNase (p=0.296). Both DNase and placebo were less effective, in terms of life-years gained, and more costly than t-PA. When placebo was compared with t-PA-DNase, the incremental cost per life-year gained of placebo was EUR 1.6 billion, with a probability of 0.85 of t-PA-DNase being cost-effective.This study demonstrates that combined t-PA-DNase is likely to be highly cost-effective. In light of this evidence, a definitive trial designed to facilitate a thorough economic evaluation is warranted to provide further evidence on the cost-effectiveness of this promising combined intervention.

Mechanical Thrombectomy for Acute Stroke in Patients with Target and Unrelated Vessel AVMs and AVFs: A Case Series

Advances in acute and long-term poststroke care have resulted in improved survival and functional outcomes for patients who have suffered large vessel ischemic strokes. For years, tissue plasminogen activator was the mainstay of treatment for acute stroke. Its use was previously limited to patients without known comorbid intracranial vascular pathology because of concern for bleeding risk. More recently, however, the use of tissue plasminogen activator in select patients with vascular anomalies has increased and is now largely thought to be safe. With the safety and efficacy of mechanical thrombectomy now proven for large vessel occlusions (LVOs), similar investigation is needed to assess procedural safety in patients with concomitant arteriovenous (AV) malformations or fistulae. We reviewed patients treated for LVOs at our institution and those of our collaborators and identified 6 patients who were treated for LVO with either known or incidentally identified concomitant AV malformations or dural AV fistulae. We present a case series of 6 patients with nonaneurysmal intracranial vascular lesions who underwent mechanical thrombectomy for LVO without complications related to these lesions. Although limited by small size, our series adds to the literature evidence that mechanical thrombectomy for LVO can safely be performed with concomitant dural AV fistulae and AV malformations.

Abstract TP103: The Use of Tissue Plasminogen Activator for Treatment of Acute Ischemic Stroke in Patients With Various Vascular Malformations Appears to be Safe

Introduction: The number of acute ischemic stroke patients who receive IV r-tPA have been shown to be lower than those estimated to be eligible for acute thrombolysis. One potential reason providers may be hesitant to give r-tPA is fear of hemorrhagic conversion in patients with underlying vascular abnormalities. Recent guidelines changed to suggest that r-tPA administration is reasonable for unruptured, unsecured aneurysms (&lt; 10 mm). However, the reports on which this was based involved small sample sizes, warranting further study. Also, there is incomplete information regarding the risk of hemorrhagic transformation and outcomes after r-tPA use in those with other preexisting vascular abnormalities. Methods: We performed a retrospective chart review at our academic institution of 438 patients treated with r-tPA for stroke and found 56 total patients with preexisting vascular malformations at the time of treatment. We describe the vascular conditions, and used logistic regression to predict outcomes in this population. Results: The vascular anomalies included 13 intracranial aneurysms, 14 dissections, 4 cavernomas, 10 infundibula, 3 dural venous anomalies, 1 sinus venous thrombosis, 1 cortical venous varix, 1 pseudoaneurysm, 1 vertebral intimal web, 1 fenestration, 1 basilar ectasia, 1 extracranial aneurysm, 2 dolichoectasias, 2 aortic aneurysms, and 2 aortic ectasias. Mean size of aneurysms was 4.18 mm and maximal size was 8 mm. Importantly, there was no significant association with ICH or poor outcome after r-tPA. There were no cases of hemorrhagic transformation in the population who had a cerebral aneurysm(s); this included one patient with a previously coiled basilar aneurysm. Only one patient in the entire cohort had hemorrhagic transformation following r-tPA, but the patient’s blood pressure was not well controlled following balloon angioplasty and mechanical thrombectomy after tPA administration during a time of difficult intubation which likely contributed to the ICH. Conclusions: These data support the safety of IV-tPA in those with preexisting vascular malformations, and adds to the body of literature for these relatively rare conditions.

Abstract 35: Safety and Outcomes of Intravenous Tissue Plasminogen Activator in Acute Ischemic Stroke Patients With Recent Stroke: Findings From Get With the Guidelines-Stroke

Introduction: Guidelines recommend against use of Intravenous tissue Plasminogen Activator (IV tPA) in acute ischemic stroke (IS) patients with prior IS within past 3 months. However, there are limited data on the safety of IV tPA in this population. Methods: Using American Heart Association Get With the Guideline-Stroke between February 2009 and December 2015 we identified 1399 acute IS patients otherwise eligible for IV tPA but with IS within prior 3 months. Of these, 293 were treated with IV tPA. We compared them with 30,655 acute IS patients treated with IV tPA but with no prior IS history. Multivariable logistic regression models were used to evaluate association between recent prior IS (within 90 days, 1-14 days, 15-30 days, 31-90 days) with symptomatic intracranial hemorrhage (sICH) and discharge outcomes after IV tPA. Results: Age (median 80, IQR 74-87) and stroke severity as measured by NIHSS (median 11, IQR 6-18) were similar for acute IS patients treated with IV tPA with or without recent IS. However, patients with recent IS were more likely to have higher prevalence of cardiovascular risk factors. In unadjusted analysis, patients with recent IS within prior 90 days were more likely to experience sICH and in-hospital mortality and less likely to have good functional outcomes (modified Rankin Scale score, 0-1) than those with no history of IS (Table 1). On multivariate analysis, risk for sICH and in-hospital mortality was not significantly different but good functional outcomes at discharge occurred less often among patients with history of IS within prior 90 days. In a prespecified subgroup analysis, the increased risk for sICH appeared to concentrate in those with recent IS within 14 days of the acute index IS but not in later time window. Conclusions: Recent IS within 90 days is associated with increased risk of worse outcomes in acute IS patients treated with tPA. In our study, the risk of sICH after tPA was highest among those with a history of prior IS within the past 14 days.

Abstract TP162: Patterns of Pre-Stroke Atherosclerotic Stenosis and Pretreatment Collateral Status in Acute Ischemic Stroke

Background: To date, there is no consensus regarding the factors associated with collaterals in acute ischemic stroke. Our study attempts to examine variables associated with pretreatment collaterals. Methods: From our hospital stroke registry, we retrospectively recruited 115 patients with acute anterior circulation infarct considered for endovascular reperfusion therapy. Collateral score (0-3) was rated using pretreatment CT angiography. Score of 0 or 1 (≤50% filling of the occluded territory) was considered as poor collaterals. The patterns of steno-occlusion other than culprit occlusion for infarct were classified into intracranial or extracranial atherosclerotic stenosis based on the location of steno-occlusion (&gt; 50% on CTA). Results: Forty five of the 115 patients had poor collaterals. Variables (with univariate P&lt; 0.1) associated with collaterals were, as pretreatment variables, older age ( ≥65 years) (P=0.067), hypertension (P=0.034), diabetes (P=0.093), initial NIHSS (P=0.002), location of culprit occlusion for infarct (P=0.001), intracranial stenosis (P=0.003), and as treatment or post-treatment variables, use of intravenous tissue plasminogen activator (P=0.004), successful recanalization (TICI grade 2b or 3: P=0.009), symptomatic intracranial hemorrhage (P=0.004), final infarct size (P&lt;0.001). When multivariable logistic regression for poor collaterals was performed using the pretreatment variables, internal carotid artery occlusion and intracranial stenosis were significantly associated with poor collaterals (Table). Conclusions: Coincidental intracranial atherosclerotic stenosis is associated with pretreatment poor collaterals during acute stage of stroke. It might be because collateral flow is assumed to be largely dependent on flow from non-occluded intracranial arteries neighboring to culprit vascular lesion for infarct.

Abstract TMP79: Use of Intravenous Tissue Plasminogen Activator in Patients With History of Prior Stroke Plus Diabetes Mellitus

Background: Patients with history of diabetes mellitus (DM) plus prior ischemic stroke were excluded from ECASS III trial due to safety concerns. However, there are few data on use of intravenous tissue plasminogen activator (IV tPA) and risk of symptomatic intracranial hemorrhage (sICH) or outcomes in this population. Methods: Using data from the Get With The Guidelines-Stroke Registry (GWTG-Stroke) between February 2009 and September 2017 (n=1619 hospitals), we examined characteristics and outcomes among AIS patients treated with tPA within the 3-4.5 hour window who had a history of prior stroke and DM (n=2129) versus those without either history (n=16,690). Results: Compared with patients without either history, those with prior stroke and DM had a higher prevalence of cardiovascular risk factors and more severe stroke (Table). The unadjusted rates of sICH and in-hospital mortality were 4.3% vs 3.8% and 6.2% vs 5.5%, respectively. These differences were not statistically significant after risk adjustment (sICH, adjusted odds ratio [OR] 0.79[95% CI, 0.51-1.21], p=0.28; in-hospital mortality OR 0.77 [95% CI, 0.52-1.14], p=0.19). Unadjusted rate of functional independence (Modified Rankin Scale score [mRS] 0-2) at discharge was lower in those with history of prior stroke and diabetes (30.9% vs 44.8%, p=&lt;0.0001), this difference persists after adjusting for baseline clinical factors (adjusted OR 0.76 [95% CI, 0.59-0.99], p=0.04). During the study period, there were 339 patients otherwise eligible for IV tPA, arriving within 0-3.5 hours, but not treated with IV tPA due to history of prior stroke and DM. Conclusion: Among AIS patients treated with intravenous tPA within the 3-4.5 hour window, history of prior stroke plus DM was not associated with statistically significant increased sICH or mortality risk.

Gender and thrombolysis therapy in stroke patients with incidence of dyslipidemia

BackgroundWhen untreated, dyslipidemia is a higher risk factor for stroke and stroke-related mortality in men than in women. However, when dyslipidemia is treated the risk reduction is the same, but men benefited from mortality reduction more than women. Whether there is a gender difference in exclusion criteria for the use of recombinant tissue plasminogen activator (rtPA) or thrombolysis therapy in an acute ischemic stroke subpopulation with dyslipidemia is yet to be investigated.MethodIn a dyslipidemic stroke population obtained from a stroke registry, gender differences in exclusion risk factors were determined using clinical and demographic variables. Univariate analysis compared the recombinant tissue plasminogen activator (rtPA) group and the no rtPA group. Multiple regression analysis was used to determine demographic and clinical factors associated with inclusion and exclusion for rtPA in the total dyslipidemic stroke population and the subsets of the male and female population. The regression model was tested using the Hosmer-Lemeshow test, for the overall correct classification percentage. Significant interactions and multicollinearity between independent variables were examined using variance inflation factors.ResultsA total of 769 patients presented with acute ischemic stroke with incidence dyslipidemia; 325 received rtPA while 444 were excluded from rtPA. Of those excluded from rtPA, 54.30% were female and 45.72% were male. In an adjusted analysis, female patients with increased age (OR = 1.024, 95% CI, 1.001–1.047, P < 0.05), with a history of carotid artery stenosis (OR = 7.063, 95% CI, 1.506–33.134, P < 0.05), and previous stroke (OR = 1.978, 95% CI, 1.136–3.442, P < 0.05) were more likely to be excluded from rtPA. Male patients with atrial fibrillation (OR = 2.053, 95% CI, 1.059–3.978, P = 0.033), carotid artery stenosis (OR = 2.400, 95% CI, 1.062–5.424, P = 0.035), and previous stroke (OR = 1.785, 95% CI, 1.063–2.998, P = 0.028) were more likely to be excluded from rtPA.ConclusionAlthough there are some similarities in the clinical risk factors for exclusion in both male and female stroke patients with incidence of dyslipidemia, there are differences as well. Elderly female stroke patients with incidence of dyslipidemia are more likely to be excluded from rtPA, even after adjustment for the effect of confounding variables. Further research should focus on how identified clinical risk factors can be targeted and managed to improve the use of rtPA in elderly female acute ischemic stroke population with incidence of dyslipidemia.