IV tPA Research Articles

Abstract TP69: Administration of Tissue Plasminogen Activator: to Wait or not to Wait for Screening Coagulation Tests? Impact on Door to Needle Time and Symptomatic Intracerebral Hemorrhage

Introduction and Hypothesis: Administration of intravenous tissue plasminogen activator (IV tPA) is currently the only FDA approved medical treatment for acute ischemic stroke. To improve outcomes the goal is to have reduced door to needle time (DTN) to IV tPA. Guidelines recommend obtaining coagulation tests prior to IV tPA, but new prescribing information suggest physicians may not need to wait for coagulation test results in patients not on anticoagulation therapy. We assessed the hypothesis if not waiting for these tests prior to IV tPA reduced the DTN time, without affecting the rate of symptomatic intracerebral hemorrhage (SICH). Methods: The study is a retrospective analysis of prospectively collected data on acute ischemic stroke patients treated at a Joint Commission Certified Stroke Center. Based on differing physician practices, patients received IV tPA prior to results of screening coagulation tests or they received IV tPA after tests returned. Measures obtained from chart review included initial NIH stroke scale (NIHSS), DTN time, lab return time, abnormal lab results, and development of post IV tPA SICH (defined as ICH associated with an NIHSS increase ≥4). Results: From January 2013 to May 2015, 136 patients received IV tPA. (Mean age ± SD = 65 ± 15 years, 53% male, 46% African American, 51% Caucasian, and 2% other, median NIHSS = 10, mean DTN ± SD = 65 ± 35 min). Group one, 102 patients, received IV tPA after test results were available (Mean age ± SD = 66 ± 15 years, 51% male, 50% African American, 48% Caucasian, and 2% other, median NIHSS = 10, mean DTN ± SD = 71 ± 34 min). Group two, 34 patients, received IV tPA prior to test results being available (Mean age ± SD = 64 ± 15 years, 59% male, 35% African American, 62% Caucasian, and 3% other, median NIHSS = 12, mean DTN ± SD = 46 ± 31 min). Group two had a significantly reduced DTN time (t test p<0.0002). No abnormal screening coagulation tests were found upon final review. There was no difference between in the rates of SICH (group one 4%, group two 6%, Fisher's exact test p>0.99). Conclusions: Selection of appropriate patients to receive IV tPA without waiting for screening coagulation tests to be returned, significantly improved DTN time. There was no significant difference between the rates of SICH in the two groups.

Abstract WP84: Thrombolysis is Safe in the Nonagenarians With Acute Ischemic Stroke

Introduction: People aged 90 years or older are the fastest growing group in North America. This group was excluded from traditional clinical trials of intravenous tissue plasminogen activator (iv tPA) thrombolysis. IV tPA is the most beneficial emergent therapy in acute ischemic stroke (AIS). We have compassionately treated AIS patients in this age group with iv tPA in recent years. Hypothesis: Our aim is to evaluate the safety and outcome of iv tPA use in nonagenarian patients with AIS Methods: Consecutively iv tPA-treated AIS patients who were older than 90 years and were admitted at our institution from January 2004-June 2015 were included. The administration of iv tPA was within 3 hours after the stroke onset. We reviewed the clinical features of the patients at presentation, complications, and outcomes. Outcome measures at discharge included improvement of NIHSS, mRS, symptomatic intracranial hemorrhage (sICH), and discharge disposition. We also assessed the rate of complications of iv tPA. Multiple logistic regression analysis was used to evaluate association between the outcome versus the severity of stroke, or versus pre-stroke dependence. Results: A total of 35 AIS patients who were 90 years or older (female 80%; and median age 93 years old) were treated with iv tPA. At baseline twenty-two patients (62.9%) had a history of atrial fibrillation without anticoagulation, and more than half (20/35) patients needed assistance for gait instability, but they were otherwise functional. Median NIHSS on admission was 16 (IQR 9-22). Two patients (5.7%) had symptomatic intracerebral hemorrhage. At discharge the median NIHSS was 10 (IQR 1-19). Ten patients (28.6%) had favorable outcome (mRS ≤ 2) while sixteen patients (45.7%) had good outcome (mRS ≤ 3). Four patients were discharged home and 16 patients went to rehabilitation facility. Fifteen patients (42.9%) succumbed to cardio-pulmonary failure or were discharged to hospice. Mild AIS patients (NIHSS <7) had better outcomes (p < 0.05). The pre-existing dependence (mRS ≥3) did not predict poor outcome. Conclusion: It is safe to administer iv tPA to AIS patients who are 90 years or older although the benefits are less robust compared to younger patients. Patients with milder deficits had more favorable outcomes.

Abstract TP70: Short-term Outcomes Among Patients With Delayed Arrival or Uncertain Onset Who are not Treated With Iv Tpa Compared to Those With Guideline-based Tpa Treatment

Intro: Unclear onset time with delayed arrival is a common reason for non-treatment with tPA. The MR-WITNESS trial is studying if arrival 4.5 h from last known well, favorable clinical factors and FLAIR signal intensity ratios can safely select patients for IV tPA. We performed a retrospective analysis to compare patient outcomes between tPA patients treated within 4.5 h vs. potential MR WITNESS candidates who did not receive tPA. Methods: Using our local GWTG-Stroke database we identified 515 patients from 1/2009 through 6/2015 who met study criteria. Patients were defined as potential candidates for MR WITNESS based on a subset of the trial inclusion criteria that were available in our dataset: they met onset time criteria (arrived >= 4.5 but <24 h from last known well, <4.5 h from symptom discovery), did not receive on-label IV tPA or thrombectomy, had NIHSS<=25, blood glucose 50-400 mg/dL and no current oral anticoagulant treatment. Because they did not get acute MR, imaging criteria could not be evaluated. Univariate and multivariable testing were performed to identify predictors of discharge home. Results: In univariate testing compared to tPA patients, potential MR WITNESS candidates were less likely to arrive by EMS, more likely to have carotid stenosis, dyslipidemia and prior stroke/TIA, and had lower median NIHSS. Despite lower NIHSS, they were less likely to ambulate independently at discharge or be discharged home. On multivariable analysis, only potential MR Witness eligibility (aOR=0.37 (0.23,0.59); p-value=0.001) and lower NIHSS (aOR=0.86 per point (0.83,0.90); p-value<0.001) were independently associated with discharge home. Conclusion: Patients who may be potential candidates for extended window IV tPA per MR WITNESS protocol have poor outcomes when untreated compared to patients who present early and are treated with IV tPA. Further research is warranted to determine if tPA treatment in this cohort can improve outcomes.

Abstract WMP71: Multimodal Imaging Yields Low Number of Stroke Mimics Treated With Thrombolytic Therapy Without Sacrificing Door-to-Needle Times

Introduction: Speed is critical in fibrinolytic therapy for acute ischemic stroke (AIS), but rapid decision-making may increase tPA use in stroke mimics. Complications from lytics in mimic patients, though uncommon, can be severe. Mimic treatment rates when using non-contrast CT as the only initial imaging modality have increased to as high as 34% with intensified efforts to reduce door to needle (DTN) times. Efficient imaging with MRI or multimodal CT may potentially avoid high mimic treatment rates without prolonging treatment. Methods: In a prospectively maintained registry, we examined all patients treated with IV tPA from January 2010 to June 2015. Institutional policy was to perform MRI first in AIS patients and start tPA on the MR table after DWI showed ischemia and GRE excluded hemorrhage; if MRI could not be performed, multimodal CT with CTA and CTP was performed. Results: Among 319 IV tPA treated patients, age was 71 (±15), 50% were female, and NIHSS was 13.3 (±8.0). Imaging modality before tPA was MR in 193 (61%) and CT in 126 (39%). In the entire population, the DTN time was 54 (IRQ 42-73) mins and the proportion of mimic patients was 3.1%. DTN times decreased steadily throughout the 5.5 year study period, and did not differ among patients imaged with MR vs CT (Figure). The reduction in DTN times was not associated with an increase in mimic-treated rates (Figure). Among the mimic patients, final diagnoses were migraine - 4, seizure - 3, meningitis - 1, PE - 1, and cardiac dysrhythmia - 1. Imaging modalities in mimic patients were MRI in 5 and CT in 5. Preliminary imaging reads suggested abnormality in 2/10, but final reads were normal in all. In 3/10 mimic patients, tPA infusions were stopped before full dose when ongoing imaging further clarified diagnosis. Conclusion: A rapid stroke assessment protocol using MRI or multimodal CT permits swift start of thrombolytic therapy and low rates of stroke mimic treatment. Figure. Door-to-needle time and percent stroke mimics by year.

Abstract WP33: Anticoagulation, Mechanical Thrombectomy and rTPA: an Outcome Analysis

Background: There is paucity of data on safety outcomes in the subgroup of patients who are on anticoagulation (AC) that undergo mechanical thrombectomy (MT) for anterior circulation large vessel stroke (AS). Methods: The Healthcare Cost and Utilization Project's (HCUP) Nationwide Inpatient Sample (NIS) data was queried between 2006 and 2010 using validated ICD 9 diagnostic codes for acute ischemic stroke. ICD-9 99.1 for IV tPA and ICD-9 procedure code 39.71 (mechanical thrombectomy) were used. Patients with AS treated with MT were divided into three groups: 1. On AC not receiving iv tPA, 2. On AC receiving iv tPA, 3. Not on AC. Group 3 was subdivided into 3a. Received iv tPA and 3b. Did not receive iv tPA. Mortality, hemorrhagic transformation (HT) and disability at discharge were used to compare outcomes. In addition to demographics, comorbid vascular risk factors, concurrent use of antiplatelet agents, in-hospital complications (DVT, PE, sepsis, hospital acquired infections) were controlled. Patients on novel oral anticoagulants were excluded. Results: A total of 10,475 AS patients received MT: Group 1- 398 (3.8%), Group 2 - 439 (4.1%), and Group 3 - 9638 (92.1%). Group 3A - 3918 (37.4%) and 3B - 5719 (54.6%). After controlling for confounders, there was no statistically significant increase in the risk of mortality, hemorrhagic transformation and disability at the time of discharge (Table) in Cohort 1 vs. to other cohorts. Conclusion: The subgroup of patients who are on AC receiving MT for AS with or without tPA did not have an increased risk of HT, mortality or disability.

Abstract WP26: Validation of Predictive Scales of Functional Outcome After Endovascular Therapy Using the REVASCAT Data

Introduction: Various scales have been developed to predict long-term clinical outcome after endovascular therapy (EVT) in stroke patients. The objective of this study was to validate and compare five well-validated scales in terms of predictive accuracy for functional independence in a recent endovascular stroke trial (REVASCAT). Hypothesis: We hypothesize that predictive scales (PRE, THRIVE, HIAT2, SPAN-100, FAR) have good-excellent (AUC>0.7) predictive accuracy for good functional outcome and can predict the beneficial effect of EVT demonstrated in randomized clinical trials. Methods: REVASCAT (Randomized Trial of Revascularization with Solitaire-FR Device versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting within Eight Hours of Symptom Onset) enrolled 206 patients who were randomized to receive EVT or best medical treatment. Five scores (PRE-score, THRIVE, HIAT2, SPAN-100 and FAR-score) were retrospectively calculated on patients who received EVT. Receiver-operator characteristics (ROC) for good outcome (mRS 0-2 at 90 days) for each scale were compared. Using the highest predictive scales, the proportion of patients with good outcome by the score categorized in quartiles was analyzed. Results: 103 patients received EVT in the REVASCAT trial (mean age 65.7, median NIHSS 17). Baseline NIHSS, baseline CT-ASPECTS, age and atrial fibrillation, but not previous iv tPA or DM, were associated with good outcome in multivariable analysis. AUC for good outcome was ≥0.70 for FAR (0.74) and PRE (0.70) scores while SPAN-100 (0.67), HIAT2 (0.65) and THRIVE (0.64) had lower AUCs although differences were not statistically significant. The higher the score on the PRE and FAR scores, the lower the proportion of patients with good outcome (PRE-score: 1QT 44.4%, 2QT 24.4%, 3QT 22.2%, 4 QT 8.9%; FAR-score: 1QT 57.8%, 2QT 22.2%, 3QT 6.7%, 4QT 3.3%). Benefit of EVT accordingly to the score on the different scales will be also presented. Conclusions: Of the 5 stroke scales, FAR and PRE had better predictive accuracy for functional independence after EVT. These tools may facilitate decision making for EVT in anterior circulation large vessel occlusion stroke.

Imaging Evidence for Cerebral Hyperperfusion Syndrome after Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke.

Background. Cerebral hyperperfusion syndrome (CHS), a rare complication after cerebral revascularization, is a well-described phenomenon after carotid endarterectomy or carotid artery stenting. However, the imaging evidence of CHS after intravenous tissue plasminogen activator (iv tPA) for acute ischemic stroke (AIS) has not been reported. Case Report. Four patients were determined to have manifestations of CHS with clinical deterioration after treatment with iv tPA, including one patient who developed seizure, one patient who had a deviation of the eyes toward lesion with worsened mental status, and two patients who developed worsened hemiparesis. In all four patients, postthrombolysis head CT examinations were negative for hemorrhage; CT angiogram showed patent cervical and intracranial arterial vasculature; CT perfusion imaging revealed hyperperfusion with increased relative cerebral blood flow and relative cerebral blood volume and decreased mean transit time along with decreased time to peak in the clinically related artery territory. Vascular dilation was also noted in three of these four cases. Conclusions. CHS should be considered in patients with clinical deterioration after iv tPA and imaging negative for hemorrhage. Cerebral angiogram and perfusion studies can be useful in diagnosing CHS thereby helping with further management.

A Teenager With an Acute Stroke While at School

Acute stroke in children is an uncommon occurrence. We present a 16 year old adolescent boy who developed acute left hemiparesis while at school and 911/ EMS was called and received iv tpa and made an excellent recovery. We discuss potential challenges to stroke recognition and treatment in children.

Should CT Angiography be a Routine Component of Acute Stroke Imaging?

Should CT Angiography be a Routine Component of Acute Stroke Imaging?

Thrombectomy in patients ineligible for iv tPA (THRILL).

A relevant proportion of patients with acute ischemic stroke are ineligible for intravenous thrombolysis with recombinant tissue plasminogen activator. Mechanical thrombectomy offers a treatment alternative for these patients; however, only few data are available on its safety and efficacy. The aim of this study was to compare safety and efficacy of stent retrievers as device class with best medical care alone in acute stroke patients with large intracranial vessel occlusion in the anterior circulation who are not eligible for intravenous thrombolysis with recombinant tissue plasminogen activator up to eight-hours of symptom onset. 'Thrombectomy in patients ineligible for iv tPA' is a prospective, open-label, blinded end-point, binational (Germany and Austria), two-arm, randomized, controlled, post-market study. Primary end-point is the modified Rankin Score shift analysis 90 days (±14) after stroke. Secondary end-points are excellent neurological outcomes (modified Rankin Score ≤ 1), good neurological outcomes (modified Rankin Score ≤ 2 or National Institutes of Health Stroke Scale improvement ≥ 10), difference between predicted infarct volume and actual core infarct volume (computed tomography or magnetic resonance imaging) at 30 (±6) h post-ictus, successful recanalization (thrombolysis in cerebral infarction score 2b or 3), functional health status 90 (±14) days after stroke (European Quality of Life-5 Dimensions) as well as common safety end-points (adverse event, serious adverse event, symptomatic intracranial haemorrhage at 30 (±6) h, death, or dependency). Whether mechanical thrombectomy in patients with acute ischemic stroke who are not eligible for intravenous thrombolysis with recombinant tissue plasminogen activator improves clinical outcomes is unclear. 'Thrombectomy in patients ineligible for iv tPA' may change clinical practice by providing evidence of an effective and safe treatment for such patients.

Abstract T P346: ‘Expedite For Thrombolytic’ Patient Designation and Early Ordering for Improved Door-to-Needle Times in Acute Ischemic Stroke

Purpose: The American Heart Association’s ‘Target: Stroke Phase 2’ (TS2) ‘door-to-needle’ time sets a goal for IV tPA administration of <45 minutes in >50% of eligible patients. In order to meet this goal we delineated a set of patient characteristics which would trigger an expedited pathway for IV tPA administration. These characteristics included a well documented time of onset, obvious and significant stroke and no history of anticoagulant use. We then used this patient group to implement processes to decrease door to needle time. Methods: A retrospective cohort of 35 IV tPA, ED-administered cases from 5/2013-2/2014 were reviewed. DTN <60 minutes was achieved in 22 cases (62.9%, mean 62.0 min, median 45.0 min). EMS, field-initiated stroke codes expedited evaluation in 65.7% of patients. Turn-around-times (TAT) in Stroke Code processes (non-contrast head CT and laboratory results) demonstrated 95.7% compliance with benchmark times. The time of presentation to orders received for IV tPA revealed a mean of 48.8 min and median of 45.0 min. Cases with DTNs >60 minutes (n=13), documented reasons include family indecision (38.5%), blood pressure management (15.4%) and other (46.1%). Results: Neurologists, ER physicians, nursing, pharmacy, and radiology used the data to construct a new, consistent processes to safely deliver IV tPA in <45 minutes. In the first 90 days, ED IV tPA times (N=16) dropped to 48.5 min, median 49.5 min. The expedite-for-thrombolytic principle ‘to treat unless excluded’ aligns and assists in meeting the benchmarks identified in TS:2 (goal IV tPA <45 minute DTN). Additional research is needed to identify time-reducing means while improving patient stroke outcomes.

Abstract W MP104: tPA Administration and Dosing Errors within a Regional Stroke System

BACKGROUND: Utilization of systemic IV tPA in acute ischemic stroke (AIS) requires weight-based dosing and a standardized infusion rate. We describe the frequency and types of tPA administration errors made in a comprehensive stroke center (CSC) and at stroke receiving facilities prior to transfer. METHODS: Using a prospectively-collected stroke quality database, all patients included received IV tPA from 2010-11 either at the CSC or prior to transfer (“drip-and-ship”). Retrospective data collection included pharmacy, air transport, and nursing records. RESULTS: We identified 131 tPA-treated AIS cases: 51% female; mean age 68 years; 33% treated at CSC; and 67% treated pre-transfer (including 16% by telestroke) from 22 facilities. Treatment of stroke mimics was more common at the CSC (12% vs 9%, p=NS). Pre-tPA blood pressure was more frequently not recorded in transfers (64% vs 7%, p<0.0001). tPA dosing/administration errors were present in 49.6% of all patients (26% at CSC; 61% of transfers, p=0.0001): infusion > 60 minutes (14%), total dose >90mg (5%), suspension/discontinuation of infusion (5%), or delayed tPA delivery to bedside (4%). Body weight discrepancies between institutions were frequent among transfers (42%). Parenchymal hematomas (PH) occurred in 7.5% of all patients (or 6.2% with tPA errors, 9.1% without errors); in-hospital death occurred in 10.7% overall (or 9.2% with errors, 12.1% without errors). PH, mortality and mRS did not differ between CSC-treated patients and transferred patients nor between those with and without errors. See table. CONCLUSION: tPA errors were very common in our large, regional stroke system, particularly among patients treated as “drip-and-ships”. Though in this study errors were not associated with outcomes, CSCs should include tPA dosing/administration education and quality assurance mechanisms within their systems in order to reduce avoidable, systematic errors.

Abstract T P34: Poor Collateral Circulation Assessed By Multiphase Cta Predicts Malignant Mca Evolution After Reperfusion Therapies

Background: Collateral circulation (CC) has been associated with recanalization, infarct volume, risk of haemorrhagic transformation and clinical outcome in patients undergoing acute reperfusion therapies. However, its relationship with the development to malignant MCA infarction (mMCAi) has not been evaluated. Our aim was determine the impact of collateral circulation using multiphase CTA (mCTA) on acute phase in the prediction of mMCAi. Methods: Consecutive acute stroke <4.5h patients that were evaluated for reperfusion therapies and with a M1-MCA or TICA occlusion by CTA were included. CC was evaluated on mCTA, CC evaluation was performed according to the University Calgary CC Scale; CC was also classified as poor (grades 0-3) or good (grades 4-5). The mMCAi was defined according to previously published clinical and radiological criteria. Recanalization was assessed with TCD at 24-hours and TICI score≥2a in endovascular treatment (ET) patients. Good outcome was defined as mRS 0-2 at 3months. Results: 82 patients were included. Mean age: 65.1 ±13.83 years, median baseline NIHSS 18(IQR 5.7), 67.9% M1 and 32.1% TICA occlusions, 53 patients received ET and 57 iv tPA, 15 patients develop a mMCAi. In the univariate analysis, patients with mMCAi had lower CC scores (2.29 Vs. 3.71 p=0.001), higher baseline NIHSS (19.86 Vs. 15.70 p=0.016), lower TIMI reperfusion scores (0 Vs. 2.79 p=00.5) and presence of TICA occlusion was more often compared with M1 occlusion (71% Vs. 11.9%, p=0.033) ET was associated with lower rate of mMCAi development as compared with only i.v. reperfusion treatment (9.4%Vs.29.6%, p=0.028). Furthermore, all patients with poor CC who did not recanalize developed mMCAi (6 Vs. 0, p=0.68) On the multivariate analysis adjusted to age, vessel occlusion, baseline NIHSS and recanalization, the presence of poor CC by mCTA was the only independent predictor of mMCAi (p=0.048 OR: 9.72, 95%IC: 1.387-92.53) Conclusion: CC assessment by mCTA independently predicts malignant MCA progression. In patients with persistent occlusion after reperfusion therapies, the presence of poor CC may help in the early malignant MCA detection and management.

Abstract 19483: Assessment of Outcome in Patients With Acute Minor Ischemic Stroke Treated With Intravenous TPA

Introduction: Minor acute stroke (NIHSS≤4) within 4.5 hours from symptom onset is a common reason for withholding intravenous (iv) Thrombolysis (TPA), due to potential risk of major bleeding with such treatment and assumed good outcome without intervention. This subgroup of patients was excluded from the landmark NINDS iv tPA trial as per the prespecified protocol and also from various recent clinical trials involving acute stroke. In a recent study of patients with Rapid Improving symptoms and Minor stroke who did not receive IV tPA, 28.3% could not be discharged home and 28.5% could not ambulate independently at the time of discharge (Smith et al 2011). The efficacy of iv TPA in Minor stroke has not been previously studied. Method: Retrospective review of consecutive patients with Minor stroke (NIHSS ≤4) arriving within 4.5 hours between January 2009-July 2013 was done. Outcome in patients who received IV TPA was compared with patients who did not receive any IV tPA. Good outcome was defined as mRS ≤2. Results: 186 patients were identified out of which 20 received iv tPA. The baseline median NIHSS was 2 in the non-intervention group vs 3 in the intervention group (p =0.001), more cardioembolic, cryptogenic and lacunar stroke in tPA group (40% vs 35.53%, 20% vs 14.46% and 30% vs 22.89% respectively) there was no other statistically significant difference between the baseline characteristics of the two groups. Median change in NIHSS from admission to discharge was 1 for non-tPA vs 2.5 for tPA(p<0.001) and good outcome at discharge was seen in 80% patients in tPA vs 69.28% in non-tpa group (p =0.321). 8-12 week follow up data was available for 100 patients (12 tPA patients). Mean mRS was 1.34 in non-tPA vs 1 in tPA group (p=0.430) Conclusion: Acute intervention in Minor stroke appears to be safe. We did not find any statistically significant difference in clinical outcome between the two groups; this is likely due to small sample size, short follow-up period, and other confounding factors that we cannot fully account for in a retrospective study. A prospective randomized control study is warranted to clearly delineate the effect of iv TPA in patients with Minor stroke.

E-008 Clinical and Radiographic Outcome of Acute Ischemic Stroke Patient who Presented with Middle Cerebral Artery Occlusion-A Single Center Experience

BackgroundRecent stent retrieval thrombectomy trial demonstrates that better clinical outcome depends on the better recanalization of the occluded artery and better collateral flow may improve outcome. The MCA occlusion may...

Abstract W P47: Recanalization After IV TPA Alone Among Acute Ischemic Stroke Patients Treated With Combined IV-Endovascular Recanalization: Impact of Arterial Occlusion Site

Background: Combined IV TPA and catheter-based reperfusion is an emerging treatment strategy for acute ischemic stroke. Both patient care and clinical trial design would be enhanced by delineation of which patients rapidly respond to IV TPA alone, before endovascular therapy can be initiated. Methods: In a prospectively maintained registry of patients treated under a general policy of combined IV TPA and endovascular therapy, we analyzed subjects with MRA/CTA-confirmed anterior circulation occlusions prior to IV TPA start. Results: Among 118 patients meeting study entry criteria, age was mean 71.5 (SD 14.5), 53.0% were female, and baseline NIHSS was 14.4 (SD 7.1). Confirmed sites of occlusion prior to IV TPA were internal cerebral artery (ICA) in 22.9%, M1 segment of middle cerebral artery (MCA) in 50.0%, and M2-3 in 27.1%. Among patients undergoing catheter cerebral angiography, median time from start of IV TPA to diagnostic catheter angiogram was 75 mins (IQR 50-113). A total of 48 (40.7%) patients achieved partial or complete recanalization (AOL 2-3) of the initial target artery with IV TPA alone (partial in 22 (18.6%) and complete in 26 (22.2%)); an additional 44 (37.3%) achieved partial or complete recanalization after endovascular therapy. Recanalization rates after IV TPA alone varied by target occlusion site: ICA - 22.2%, M1 - 40.7%, and M2-3 - 56.2%. In multivariate logistic regression analysis, independent predictors of recanalization with IV TPA alone were: M2-3 clot location, OR 3.04 (95% CI 1.20-7.73, p=0.019) and TOAST etiology large-artery atherosclerosis, OR 0.14 (CI 0.04-0.50, p = 0.003). Good outcome (mRS ≤ 3) rates at 3 months were 76.6% among recanalizers with IV TPA alone and 47.5% among recanalizers after both IV TPA and catheter therapy. Conclusions: When combined IV-endovascular treatment is pursued, recanalization with IV TPA alone occurs in 4 out of 10 patients before catheter therapy is started, is more common with more distal clot location, and is associated with a high rate of excellent clinical outcomes.

Abstract W P1: Efficacy of IV TPA in Endovascular Trials: A Pooled Analysis

Background: IV TPA is the comparator for many studies of endovascular therapies (EVT) in acute ischemic stroke. We analyzed the efficacy of IV TPA reported in recent large EVTs and compared it to earlier studies. Our hypothesis was that the perceived failure of various therapies in recent EVT trials was due to the unanticipated efficacy of IV TPA alone and not the failure of EVT. This may have adversely affected the design and power assumptions of recent trials. Methods: We analyzed baseline and outcome data from recent large trials of IV TPA vs placebo and IV TPA alone vs various EVTs with or without IV TPA. Studies included were ECASS I-III, ATLANTIS, NINDS, SITS-MOST, EPITHET, IMS3, and SYNTHESIS. Onset to treatment times, age, and baseline NIHSS scores were examined. The primary outcome was a modified Rankin of 0-2 at 3 months for the IV TPA only patients. When possible we analyzed patients treated 4.5 to 6 hr after symptom onset to mirror the treatment delays seen in EVT. Results: Across all studies there were 8736 IV TPA only treated patients. The median age was consistent across all trials (67-68 years), as was the mean NIHSS score (11-13 for all, except for 16 in IMS3). Good outcomes were achieved in 40% to 46% of IV TPA only treated patients in the EVT trials compared to 49% for those treated in IV TPA vs placebo trials and 55% treated in open-label IV TPA registries. Limiting the analysis to patients treated 4.5 to 6 hr after stroke onset showed 49% of patients had a good outcome with IV TPA alone vs placebo. One EVT trial under-estimated the efficacy of the IV TPA only arm, with an assumed good outcome rate of only 40% (vs 46% in the actual trial). Conclusions: Among patients enrolled in EVT trials, IV TPA alone performs quite well, with up to 46% of patients having a good outcome. Any EVTs will have to demonstrate robust efficacy to show a superior clinical benefit when compared to IV TPA alone.

Abstract T P1: Higher Recanalization Rate with Stentrievers, but Outcome Not Improved

Introduction: Intraveneous (iv) recombinant tissue plasminogen activator (tPA) is the evidence based treatment in acute stroke. Intraarterial treatment with tPA and/or instrumentation of the vessel with the attempt to manipulate the clot and remove it (called Intra Arterial Therapy (IAT)) is emerging as a tool for treating patients with contraindications to iv tPA or for patients with large clot burden, where iv tPA is often unsuccessful. IAT has been shown to have better recanalization rates than iv tPA (1), but in a randomized trial, IAT did not prove itself better than traditional iv tPA (2). Stentrievers (ST) are a new form of removable stent and it has shown promise in improving recanalization and outcome in IAT (3). Materials and methods: At our institution, 237 patients underwent IAT from 2004-2012. STs were used as part of the recanalization procedure in 92 patients. Results: Recanalization (defined as TICI 2b or 3) was achieved among 76 of the 92 patients=83 % in the ST group and in 61/145=42 % of the patients in the non-ST group, giving an odds ratio (OR) for recanalization using ST on 6.54 (p<0.0001). Good outcome defined as a modified Rankin Score (mRS) of 0-2 90 days after the stroke was achieved among 44/92=48% in the ST group and among 63/145=43% in the non-ST group. There was no statistical difference between these rates. Univariate analysis showed no differences in demographic data between ST and non-ST groups: Mean age 68 vs. 67 years (p=0.37), mean presenting NIHSS 17 vs. 16 (p=0.07) and time to groin puncture was 235 minutes in the ST group and 240 minutes in the non-ST group (p=0.17) (Mann-Whitney test). Conclusion: Recanalization is important for good outcome, but even though recanalization was achieved much more often in the ST group, this did not translate into better outcomes. Our findings are in line with the SWIFT study (3) where outcome defined as mRS 0-2 after 90 days were also not different between the ST group and the MERCI group. Manipulating the clot with the risk of distal embolization has been speculated to offset the benefit of recanalization (4).

Abstract 187: Impact of General Anesthesia on Safety and Outcomes in the Endovascular Arm of IMS III

Objectives: Use of general anesthesia (GA) during endovascular therapy (ET) of AIS patients is controversial with some suggestion of worse outcomes and death. The IMS III trial permitted the study of the effect of GA in a prospectively collected data set to test two hypotheses: (1) intubation is associated with poorer outcomes and (2) there is no increase in the risk of SAH or sICH with local anesthesia (LA). Methods: IMS III was a randomized trial of IV tPA +/- ET in patients presenting within 3hrs of AIS onset. In addition to demographic and outcomes data (mRS, ICH, etc.), information was collected on GA use or not within 7hrs of stroke onset. A good outcome was defined as mRS≤2 at 90 days. A multivariable analysis adjusting for dichotomized NIHSS (8-19 vs. ≥20), age and time from onset to groin puncture was performed. Additional analyses of reasons for intubation are ongoing and will be part of the presentation. Results: Four-hundred-thirty-four patients were randomized to ET, 269(62%) with LA and 147(33.9%) with GA. They were evenly matched in demographics, medical comorbidities, time to tPA, time to groin puncture, 40minute post IV tPA bolus SBP and occlusion location/side. The baseline NIHSS were slightly lower in the LA group (median 16 vs. 18). The GA group was less likely to achieve a good outcome (RR 0.64, CI 0.49-0.84, p=0.001) and had a greater risk of in-hospital death (RR 3.11, CI 1.86-5.20, p<0.0001). There was an increased risk of SAH in the GA group (RR 1.79, CI 1.04-3.08, p=0.0364) but no statistically significant difference in sICH (RR 1.69, CI 0.79-3.61, p=0.18). The multivariable analysis confirmed the negative association between GA and good outcomes (RR 0.68, CI 0.52-0.90, p=0.0027). Conclusions: In the IMS III trial there was an association with worse neurological outcomes and increased mortality with ET under GA. Also, there was an association between GA and an increased risk of SAH. Although the reasons for these associations are not clear, these data support the use of LA when possible during ET.

Abstract T P46: Absence of a Very Low Cerebral Blood Volume (VLCBV) Lesion Identifies Patients Who Are Unlikely to Have Hemorrhagic Transformation After Delayed Endovascular Reperfusion

Objective: Ischemic stroke patients with areas of VLCBV on baseline imaging are at increased risk for hemorrhagic transformation following iv tPA induced reperfusion. The underlying hypothesis is that regions of low CBV are highly susceptible to reperfusion injury. We examined the DEFUSE 2 study data, and tested whether the presence of VLCBV assessed with an automated software tool predicts the risk of hemorrhagic transformation in patients treated with endovascular therapy up to 12 hours. Methods: Patients who reperfused following endovascular therapy and who had technically adequate PWI and DWI data were included. Presence of parenchymal hematoma (PH 1 or 2) was assessed blinded to clinical data by a neuroradiologist at the core lab. RAPID, a fully automated image processing program, was used for coregistration of the DWI and PWI images, removal of large vessels, processing of CBV maps, and calculation of relative CBV (rCBV) defined as a ratio of the original and the mirrored CBV maps. We first determined the rCBV threshold within the DWI lesion that had the highest area under the ROC curve (AUC) for predicting PH. We then determined the rCBV lesion volume at this threshold which best predicted PH. Results: 60 patients (82.6%) were included in this analysis, the median time between symptom onset and femoral puncture was 6.5 hours (PH vs. no PH 6.1 vs. 6.6; p = 0.5). Patients with PH and no PH had similar DWI volumes (p=0.08) and NIHSS scores (p=0.23) at baseline. Among patients who reperfused, the greatest AUC for predicting PH was present at an rCBV threshold of 0.3 (AUC 0.707). At this threshold, an rCBV volume of >0.86 ml optimally predicted PH with a sensitivity of 0.93 (95%CI 0.66 - 1.0), specificity of 0.52 (95%CI 0.37 - 0.67), negative predictive value of 0.89 (95%CI 0.71-0.98) and positive predictive value of 0.35 (95%CI 0.23-0.49). Conclusions: PH following endovascular reperfusion can be predicted with high sensitivity and high negative predictive value with an automated image processing tool. The optimal threshold for predicting PH is an rCBV(<30%) lesion volume of ≥0.86 ml. Patients with rCBV(<30%) lesions smaller than this threshold are very unlikely to suffer a parenchymal hematoma following reperfusion.