Abstract W P61: Safety and <i>E</i> fficacy of <i>I</i> ntravenous <i>E</i> ptifibatide as <i>S</i> tandalone <i>T</i> herapy for select <i>A</i> cute Ischemic Stroke Patients (SIESTA-I trial)

Background and Objective: There is existence of data on the successful application of Eptifibatide, a cyclic heptapeptide inhibitor of glycoprotein IIb/IIIa receptor with its short half-life in coronary interventions. There is minimal literature in the application of stroke treatment. Our objective was to report the results of an open labeled retrospective registry to evaluate the safety (in regards to hemorrhagic complications) and efficacy (regarding discharge NIHSS) of administering high dose IV Eptifibatide as a standalone therapy for acute stroke in patients ineligible for IV r-tPa or neurointervention. Methods: All patients with acute ischemic events between 2010-13 were included that presented to our university affiliated comprehensive stroke center. Patients that received Eptifibatide as standalone therapy were reviewed. Eptifibatide was administered intravenously as a 135-μg/kg single-dose bolus, then a 0.5-μg/kg/min infusion. Charts were reviewed for all patients to assess for primary safety and efficacy endpoint. The primary safety endpoint was bleeding. Bleeding complications were classified as major (symptomatic intracranial hemorrhage and hemoglobin decrease by &gt;5mg/dl), minor (hemoglobin decrease 3-5 mg/dl) and insignificant as proposed by the TIMI score (Thrombolysis in Myocardial Infarction). The primary efficacy end point was neurological improvement/deterioration as defined by a change in discharge NIHSS by &gt; 4 points compared to initial NIHSS respectively. Results: Of a total patient population of 2,329, total of 20 patients (mean age of 73, 50% male (n=10)) received Eptifibatide administered intravenously for a mean duration of 32.5 hours (range 17-67 hours). No major or minor bleeding was observed except for a patient who exhibited minor complication of knee hemarthroses. 9 patients demonstrated early neurological improvement with only 2 exhibiting neurological deterioration related to extension of ischemic core. Conclusion: Application of IV Eptifibatide in achieving recanalization and preventing extension may be a safe standalone therapy in acute ischemic stroke patients ineligible for other neurological interventions. Larger randomized trials are required to corroborate our findings. </jats:p

Ischemic Stroke Occurs Less Frequently in Patients With COVID-19

Background and Purpose: The impact of coronavirus disease 2019 (COVID-19) on the occurrence of ischemic stroke has been the subject of increased speculation but has not been confirmed in large observational studies. We investigated the association between COVID-19 and stroke. Methods: We performed a cross-sectional study involving patients discharged from a healthcare system in New York State, from January to April 2020. A mixed-effects logistic regression analysis and a propensity score–weighted analysis were used to control for confounders and investigate the association of COVID-19 with ischemic stroke. Similar techniques were used to detect the impact of concurrent COVID-19 infection on unfavorable outcomes for patients with stroke. Results: Among 24 808 discharges, 2513 (10.1%) were diagnosed with COVID-19, and 566 (0.2%) presented with acute ischemic stroke. Patients diagnosed with COVID-19 were at one-quarter the odds of stroke compared with other patients (odds ratio, 0.25 [95% CI, 0.16–0.40]). This association was consistent in all age groups. Our results were robust in sensitivity analyses, including propensity score–weighted regression models. In patients presenting with stroke, concurrent infection with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was associated with higher case-fatality (odds ratio, 10.50 [95% CI, 3.54–31.18]) and a trend towards increased occurrence of discharge to rehabilitation (odds ratio, 2.45 [95% CI, 0.81–1.25]). Conclusions: Using a comprehensive cross-section of patients from a large NY-based healthcare system, we did not identify a positive association between ischemic stroke and COVID-19. However, patients with stroke with COVID-19 had worse outcomes compared with those without, with over a 9-fold increase in mortality. Although no definitive conclusions can be reached from our observational study, our data do not support the concerns for an epidemic of stroke in young adults with COVID-19. </jats:sec

Abstract W MP28: Safety of Parentral Antiplatelet Regimen Within 24 Hours of Intravenous tPA Administration: Challenging the Conventional Paradigm

Background and Objective: It is considered unconventional to initiate antiplatelet regimen within 24 hours of IV tPa administration in acute ischemic strokes. There has been an increasing amount of literature assessing combination therapy of IV r- tPA and IV Eptifibatide in acute ischemic stroke. Our objectives were to evaluate the safety (hemorrhagic complications) and efficacy (discharge mRS) of administering IV Eptifibatide within the first 24 hours of receiving full dose IV r-tPA respectively. Materials and Methods: All patients that presented to our university affiliated stroke center from 2010-13 with an acute ischemic stroke were included and retrospectively classified into two groups. Group A underwent full dose IV r- tPa (.9 mg/kg) (+/- Endovascular intervention). Group B underwent full dose IV r-tPa (.9mg/kg) and IV Eptifibatide (+/- Endovascular intervention). Epitafibide was administered as a bolus of 135 mcg/kg IV followed by .5 mcg/kg/min for 20 hours. The primary endpoint of bleeding is classified as major (symptomatic intracranial hemorrhage or hemoglobin decrease by &gt;5 mg/dl), minor (asymptomatic intracranial hemorrhage or hemoglobin decrease by 3-5 mg/dl) and insignificant as proposed by TIMI score. The efficacy endpoint was discharge mRS of 0-1 as favorable, with 2 and above being unfavorable. Results: We reviewed 2,016 patients with ischemic stroke, of which 170 received IV tPA. Among the group, 118 received IV r-tPa alone and 52 received combined modalities of IV r-tPa and IV Eptifibatide. In group A, there were 7 patients who had a major complication of symptomatic intracranial hemorrhage, while 1 patient had a minor complication of asymptomatic intracranial hemorrhage. In group B, there were 3 patients who had major complication of symptomatic intracranial hemorrhage and 5 with minor complications of asymptomatic intracranial hemorrhage. In group A , 9% (n=4) had a favorable outcome (OR=2.389, 95% CI 0.6645 to 8.589, p= 0.2217). Of the 52 patients in group B, 18% (n=8) had a favorable outcome. Conclusion: IV Eptifibatide, within the first 24 hours of ischemic stroke in combination with full dose IV r-tPA was found to be safe and efficacious. Further, larger prospective trials are needed to corroborate our findings. </jats:p

Abstract W P307: <b>Novel Application of Reversible Parental Anti-platelets in Patients with Aneurysmal Subarachnoid Hemorrhage</b>

Background and Objective: The International Subarachnoid Aneurysm Trial (ISAT) showed a greater likelihood of survival free 1 year disability in patients undergoing endovascular coiling who were started on antiplatelet agents after SAH compared to ones undergoing neurosurgical clipping. However, data on safety of acute parental antiplatelet agents after aneurysmal coiling is lacking. We report on the safety of IV Eptifibatide (rapidly reversible Glyprotein IIbIIIa inhibitor) on patients presenting with acute subarachnoid hemorrhage undergoing endovascular coiling for aneurysmal embolization. Methods: All the patients from 2009-13 who presented to our university affiliated comprehensive stroke center with aneurysmal subarachnoid hemorrhage and underwent endovascular coiling were included for the study. Patients that received IV Eptifibatide for various reasons including acute need for stent assist coiling after securing the ruptured aneurysm with endovascular coiling were reviewed. Eptifibatide was administered intra-arterially as a 135-μg/kg single-dose bolus, and then continued on intravenous infusion of 0.5-μg/kg/min post-procedurally. Charts were reviewed for all patients to assess for medical/procedural complications including symptomatic and asymptomatic intra- and extra-cranial hemorrhages, groin hematomas, epistaxis and gross hematuria. Results: Of the total of 93 patients treated with coil embolization during this period, 5 patients (mean age 56 years, 20% male [n=1]) received acute intra-procedural Eptifibatide followed by IV infusion for a mean duration of 77 hours (range 20-130 hours). Various reasons for use of Eptifibatide included: stent assist coiling [n=2], multiple stents for flow diversion [n=1], partial coil prolapse [n=1] and vascular lumen flow compromise [n=1]. None of the patients demonstrated symptomatic/asymptomatic hemorrhage, groin hematoma, epistaxis or hematuria. Conclusion: Our results may highlight safety of administering IV Eptifibatide to prevent thrombotic complications after endovascular coil embolization in select patients with aneurysmal subarachnoid hemorrhage. Multicenter prospective trials are warranted to corroborate our findings. </jats:p

Surface Cooling System for Fever Control in Neurocritical Care Patients: A Pilot Study

OBJECTIVES: Fever occurs in up to 50% of critically-ill patients with acute neurological injury. Small temperature elevations have been correlated with increased morbidity and mortality in this patient population. We sought to evaluate a novel single-use surface cooling system for the treatment of fever in patients with acute brain injury. PATIENTS AND METHODS: We conducted a retrospective analysis of a prospective product evaluation using the EMCOOLS Flex.Pad™ system for acute fever (≥38.3 °C) in our 16-bed neuro-ICU. Four refrigerated pads (-18 °C) were applied to the chest, back, and anterior thighs. Core temperature (bladder) was continuously recorded over 4 h, and the highest Bedside Shivering Assessment Scale (BSAS) score was recorded hourly. RESULTS: Twelve subjects were included in the analysis. Mean age was 55 ± 9 years, 9 patients were men, and mean weight was 85 ± 12 kg. The most common primary diagnoses were subarachnoid (N = 5) and intracerebral (N = 4) hemorrhage. Application of the EMCOOLS system resulted in a linear 1.3 ± 0.6 °C drop (T0avg=38.9 (0)C, T90avg=37.6 (0)C, P=0.0032) in mean temperature over 90min, followed by a plateau with only one subject rebounding to \u3e38 degrees C within 4h. Normothermia (\u3c38.0 (0)C) was achieved in all but one patient (92%) in an average of 65min. Comatose patients displayed a non-significantly higher degree of cooling at 90min than did awake subjects (DeltaTcoma=1.74 degrees C vs DeltaTawake=0.74 degrees C hr(-1), P=0.067). There was no observed skin irritation upon removal of the device for any patients. CONCLUSION: The EMCOOLs system is a well-tolerated, safe and effective short-term intervention for control of fever in neurological patients. Future studies are needed to compare efficacy of the EMCOOLs to other devices and interventions

Abstract W P19: Large Single Center Experience of Safety of Parenteral Infusion and Maintenance of Antiplatelets in Patients with Acute Ischemic Stroke undergoing Mechanical Thrombectomy and Thrombolysis

Background and Objective: Lack of achieving complete recanalization in acute strokes using only IV thrombolysis has led to the evolution of a multimodal acute ischemic stroke paradigm which includes combination of intra-arterial tPA, mechanical thrombectomy and stenting. There is limited data on safety of administering intra-arterial and intra-venous antiplatelet agents within the acute stroke treatment paradigm to maintain target vessel recanalization. Methods: Of the total patients with acute ischemic strokes presented between 2010-13 to our university affiliated comprehensive stroke center, patients that received IA and IV Eptifibatide were retrospectively classified into two groups: Group A underwent emergent intracranial stenting with IV and or IA r-tPa and/or mechanical thrombectomy. Group B underwent IV r-tPa/ IA r-tPa /IA Eptifibatide and/or mechanical thrombectomy with no intracranial stenting. Eptifibatide was administered intra-arterially as a 135-μg/kg single-dose bolus, and then continued on intravenous infusion of 0.5-μg/kg/min post-procedurally. Charts were reviewed for all patients to assess for complications including groin hematoma, asymptomatic and symptomatic hemorrhages, epistaxis and gross hematuria. Results: Of the total of 2016 patients with ischemic strokes, 326 patients received acute stroke treatment and a total of 138 patients received IA and IV Eptifibatide. Group A with acute stenting (82 patients, mean age 68, 49% males [n=40]) and Group B without stenting (56 patients, mean age 73, 54% males [n=30]) received IV Eptifibatide infusion for a mean duration of 19 hours (range 0 to 364 hours). In Group A, 7.3% [n= 6] showed symptomatic ICH, 4.9% [n=4] asymptomatic ICH, 3.7% [n=3] groin hematomas, 2.4% [n=2] nose bleeds. In Group B, 7.1 % [n=4] had asymptomatic hemorrhages and 1.8% [n=1] showed gross hematuria. Conclusion: The complications of IV and IA Eptifibatide are not significantly higher than those associated with the existing acute ischemic stroke treatment paradigm. Larger, multi-centered prospective trials are warranted to corroborate our findings. </jats:p

Abstract T P19: Higher HDL Levels Increase the Risk of Intracranial Hemorrhage After Endovascular Treatment for Ischemic Stroke

Background and Objectives: Recent evidence has highlighted an inverse relationship between lipids (HDL/LDL) and ischemic versus hemorrhagic stroke. Select patients presenting with ischemic stroke within the 4.5-hour time window should receive IV tPA, and depending on symptom severity or neuroimaging, they may be treated with intra-arterial (IA) tPA or endovascular therapy. Evidence has shown elevated LDL to be a risk factor for ischemic stroke, but once a patient has an ischemic stroke elevated HDL levels may put them at risk for hemorrhagic stroke. Our objective was to determine if serum lipids had a role in increasing the risk of large intracranial hemorrhage after treatment with IV tPA and IA therapy. Methods: Patients receiving IV tPA for ischemic stroke at a major university affiliated comprehensive stroke center were evaluated from 2011-2013. The procedure notes of patients who underwent IA after IV tPA were reviewed for complications. SPSS software version 22 was used to determine Spearman’s rho correlations between serum lipids and likelihood of complications as well as other baseline parameters, and descriptive statistics with standard deviations to determine the population characteristics. Results: A total of 1,565 patients with ischemic stroke were evaluated, and 188 (mean age 74.3, 55% men) patients received IV tPA, 68 also underwent intra-arterial (IA) treatment with either IA tPA or thrombectomy and met study criteria. There were 31 males and 37 females with a mean age of 73.4 (SD=14.8). The mean NIHSS was 15.9 at admission and 7.7 at discharge (SD= 6.4 and 5.5, respectively). There were 6 instances of large intracranial hemorrhages (3 symptomatic). Patients with large ICH were significantly more likely to have higher levels of total cholesterol, HDL and LDL (r=.373, r=.323 and r=347, respectively; p&lt;.01). Conclusion: As expected, patients with elevated LDL were more likely to have severe strokes requiring endovascular treatment. However, Our data suggests that ischemic stroke patients with elevated HDL are not protected and are at increased risk of hemorrhage after intra-arterial therapy. Larger, prospective trials need to be conducted for more definite conclusions. </jats:p

Systematic Review and Pooled Analyses of Recent Neurointerventional Randomized Controlled Trials: Setting a New Standard of Care for Acute Ischemic Stroke Treatment after 20 Years

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Recent advances in the treatment of ischemic stroke have focused on revascularization and led to better clinical and functional outcomes. A systematic review and pooled analyses of 6 recent multicentered prospective randomized controlled trials (MPRCT) were performed to compare intravenous tissue plasminogen activator (IV tPA) and endovascular therapy (intervention) with IV tPA alone (control) for anterior circulation ischemic stroke (AIS) secondary to large vessel occlusion (LVO). &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; Six MPRCTs (MR CLEAN, ESCAPE, EXTEND IA, SWIFT PRIME, REVASCAT and THERAPY) incorporating image-based LVO AIS were selected for assessing the following: (1) prespecified primary clinical outcomes of AIS patients in intervention and control arms: good outcomes were defined by a modified Rankin Scale score of 0-2 at 90 days; (2) secondary clinical outcomes were: (a) revascularization rates [favorable outcomes defined as modified Thrombolysis in Cerebral Infarction scale (mTICI) score of 2b/3]; (b) symptomatic intracranial hemorrhage (sICH) rates and mortality; (c) derivation of number needed to harm (NNH), number needed to treat (NNT), and relative percent difference (RPD) between intervention and control groups, and (d) random effects model to determine overall significance (forest and funnel plots). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; A total of 1,386 patients were included. Good outcomes at 90 days were seen in 46% of patients in the intervention (p &lt; 0.00001) and in 27% of patients in the control groups (p &lt; 0.00002). An mTICI score of 2b/3 was achieved in 70.2% of patients in the intervention arm. The sICH and mortality in the intervention arm compared with the control arm were 4.7 and 14.3% versus 7.9 and 17.8%, respectively. The NNT and NNH in the intervention and control groups were 5.3 and 9.1, respectively. Patients in the intervention arm had a 50.1% (RPD) better chance of achieving a good 90-day outcome as compared to controls. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Endovascular therapy combined with IV tPA (in appropriately selected patients) for LVO-related AIS is superior to IV tPA alone. These results support establishing an endovascular therapy in addition to IV tPA as the standard of care for AIS secondary to LVO.</jats:p