Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

Diagnosis, Workup, Risk Reduction of Transient Ischemic Attack in the Emergency Department Setting: A Scientific Statement From the American Heart Association.

At least 240 000 individuals experience a transient ischemic attack each year in the United States. Transient ischemic attack is a strong predictor of subsequent stroke. The 90-day stroke risk after transient ischemic attack can be as high as 17.8%, with almost half occurring within 2 days of the index event. Diagnosing transient ischemic attack can also be challenging given the transitory nature of symptoms, often reassuring neurological examination at the time of evaluation, and lack of confirmatory testing. Limited resources, such as imaging availability and access to specialists, can further exacerbate this challenge. This scientific statement focuses on the correct clinical diagnosis, risk assessment, and management decisions of patients with suspected transient ischemic attack. Identification of high-risk patients can be achieved through use of comprehensive protocols incorporating acute phase imaging of both the brain and cerebral vasculature, thoughtful use of risk stratification scales, and ancillary testing with the ultimate goal of determining who can be safely discharged home from the emergency department versus admitted to the hospital. We discuss various methods for rapid yet comprehensive evaluations, keeping resource-limited sites in mind. In addition, we discuss strategies for secondary prevention of future cerebrovascular events using maximal medical therapy and patient education.

Maintaining Stroke Care During the COVID-19 Pandemic in Lower- and Middle-Income Countries: World Stroke Organization Position Statement Endorsed by American Stroke Association and American Heart Association.

For more than a year, the SARS-CoV-2 pandemic has had a devastating effect on global health. High-, low, and middle-income countries are struggling to cope with the spread of newer mutant strains of the virus. Delivery of acute stroke care remains a priority despite the pandemic. In order to maintain the time-dependent processes required to optimize delivery of intravenous thrombolysis and endovascular therapy, most countries have reorganized infrastructure to optimize human resources and critical services. Low-and-middle income countries (LMIC) have strained medical resources at baseline and often face challenges in the delivery of stroke systems of care (SSOC). This position statement aims to produce pragmatic recommendations on methods to preserve the existing SSOC during COVID-19 in LMIC and propose best stroke practices that may be low cost but high impact and commonly shared across the world.

Demographic Disparities in Proximity to Certified Stroke Care in the United States.

Background and Purpose: Demographic disparities in proximity to stroke care influence time to treatment and clinical outcome but remain understudied at the national level. This study quantifies the relationship between distance to the nearest certified stroke hospital and census-derived demographics. Methods: This cross-sectional study included population data by census tract from the United States Census Bureau's 2014­2018 American Community Survey, stroke hospitals certified by a state or national body and providing intravenous thrombolysis, and geographic data from a public mapping service. Data were retrieved from March to November 2020. Quantile regression analysis was used to compare relationships between road distance to the nearest stroke center for each census tract and tract-level demographics of age, race, ethnicity, medical insurance status, median annual income, and population density. Results: Two thousand three hundred eighty-eight stroke centers and 71 929 census tracts including 316 995 649 individuals were included. Forty-nine thousand nine hundred eighteen (69%) tracts were urban. Demographic disparities in proximity to certified stroke care were greater in nonurban areas than urban areas. Higher representation of individuals with age ≥65 years was associated with increased median distance to a certified stroke center in nonurban areas (0.51 km per 1% increase [99.9% CI, 0.42­0.59]) but not in urban areas (0.00 km [−0.01 to 0.01]). In urban and nonurban tracts, median distance was greater with higher representation of American Indian (urban: 0.10 km per 1% increase [0.06­0.14]; nonurban: 1.06 km [0.98­1.13]) or uninsured populations (0.02 km [0.00­0.03]; 0.27 km [0.15­0.38]). Each $10 000 increase in median income was associated with a decrease in median distance of 5.04 km [4.31­5.78] in nonurban tracts, and an increase of 0.17 km [0.10­0.23] in urban tracts. Conclusions: Disparities were greater in nonurban areas than in urban areas. Nonurban census tracts with greater representation of elderly, American Indian, or uninsured people, or low median income were substantially more distant from certified stroke care.

Pandemic Guidance for Stroke Centers Aiding COVID-19 Treatment Teams.

The coronavirus disease 2019 (COVID-19) pandemic has in some regions overwhelmed the capacity and staffing needs of healthcare systems, necessitating the provision of resources and staff from different disciplines to aid COVID treatment teams. Stroke centers have multidisciplinary clinical and procedural expertise to support COVID treatment teams. Staff safety and patient safety are essential, as are open lines of communication between stroke center leaders and hospital leadership in a pandemic where policies and procedures can change or evolve rapidly. Support needs to be allocated in a way that allows for the continued operation of a fully capable stroke center, with the ability to adjust if stroke center volume or staff attrition requires.

Prehospital Triage of Acute Stroke Patients During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has broad implications on stroke patient triage. Emergency medical services providers have to ensure timely transfer of patients while minimizing the risk of infectious exposure for themselves, their co-workers, and other patients. This statement paper provides a conceptual framework for acute stroke patient triage and transfer during the COVID-19 pandemic and similar healthcare emergencies in the future.

Recommendations for the Establishment of Stroke Systems of Care: A 2019 Update.

In 2005, the American Stroke Association published recommendations for the establishment of stroke systems of care and in 2013 expanded on them with a statement on interactions within stroke systems of care. The aim of this policy statement is to provide a comprehensive review of the scientific evidence evaluating stroke systems of care to date and to update the American Stroke Association recommendations on the basis of improvements in stroke systems of care. Over the past decade, stroke systems of care have seen vast improvements in endovascular therapy, neurocritical care, and stroke center certification, in addition to the advent of innovations, such as telestroke and mobile stroke units, in the context of significant changes in the organization of healthcare policy in the United States. This statement provides an update to prior publications to help guide policymakers and public healthcare agencies in continually updating their stroke systems of care in light of these changes. This statement and its recommendations span primordial and primary prevention, acute stroke recognition and activation of emergency medical services, triage to appropriate facilities, designation of and treatment at stroke centers, secondary prevention at hospital discharge, and rehabilitation and recovery.

Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Acute Headache

This clinical policy from the American College of Emergency Physicians addressed key issues in the evaluation and management of adult patients presenting to the emergency department with acute headache. A writing subcommittee conducted a systematic review of the literature to derive evidence-based recommendations to answer the following clinical questions: (1) In the adult emergency department patient presenting with acute headache, are there risk-stratification strategies that reliably identify the need for emergent neuroimaging? (2) In the adult emergency department patient treated for acute primary headache, are nonopioids preferred to opioid medications? (3) In the adult emergency department patient presenting with acute headache, does a normal noncontrast head computed tomography scan performed within 6 hours of headache onset preclude the need for further diagnostic workup for subarachnoid hemorrhage? (4) In the adult emergency department patient who is still considered to be at risk for subarachnoid hemorrhage after a negative noncontrast head computed tomography, is computed tomography angiography of the head as effective as lumbar puncture to safely rule out subarachnoid hemorrhage? Evidence was graded and recommendations were made based on the strength of the available data.

To Treat or Not to Treat?

Background and Purpose- The 2015 updated US Food and Drug Administration alteplase package insert altered several contraindications. We thus explored clinical factors influencing alteplase treatment decisions for patients with minor stroke. Methods- An expert panel selected 7 factors to build a series of survey vignettes: National Institutes of Health Stroke Scale (NIHSS), NIHSS area of primary deficit, baseline functional status, previous ischemic stroke, previous intracerebral hemorrhage, recent anticoagulation, and temporal pattern of symptoms in first hour of care. We used a fractional factorial design (150 vignettes) to provide unconfounded estimates of the effect of all 7 main factors, plus first-order interactions for NIHSS. Surveys were emailed to national organizations of neurologists, emergency physicians, and colleagues. Physicians were randomized to 1 of 10 sets of 15 vignettes, presented randomly. Physicians reported the subjective likelihood of giving alteplase on a 0 to 5 scale; scale categories were anchored to 6 probabilities from 0% to 100%. A conjoint statistical analysis was applied. Results- Responses from 194 US physicians yielded 156 with complete vignette data: 74% male, mean age 46, 80% neurologists. Treatment mean probabilities for individual vignettes ranged from 6% to 95%. Treatment probability increased from 24% for NIHSS score =1 to 41% for NIHSS score =5. The conjoint model accounted for 25% of total observed response variance. In contrast, a model accounting for all possible interactions accounted for 30% variance. Four of the 7 factors accounted jointly for 58% of total relative importance within the conjoint model: previous intracerebral hemorrhage (18%), recent anticoagulation (17%), NIHSS (13%), and previous ischemic stroke (10%). Conclusions- Four main variables jointly account for only a small fraction (<15%) of the total variance related to deciding to treat with intravenous alteplase, reflecting high variability and complexity. Future studies should consider other variables, including physician characteristics.

The Advanced Reperfusion Era: Implications for Emergency Systems of Ischemic Stroke Care.

Large vessel ischemic stroke is a leading cause of morbidity and mortality throughout the world. Recent advances in endovascular stroke treatment are changing the treatment paradigm for these patients. This concepts article summarizes the time-dependent nature of stroke care and evaluates the recent advancements in endovascular treatment. These advancements have significant implications for out-of-hospital, hospital, and regional systems of stroke care. Emergency medicine clinicians have a central role in implementing these systems that will ensure timely treatment of patients and selection of those who may benefit from endovascular care.

Streamlined Hyperacute Magnetic Resonance Imaging Protocol Identifies Tissue-Type Plasminogen Activator-Eligible Stroke Patients When Clinical Impression Is Stroke Mimic.

BACKGROUND AND PURPOSE: Stroke mimics (SM) challenge the initial assessment of patients presenting with possible acute ischemic stroke (AIS). When SM is considered likely, intravenous tissue-type plasminogen activator (tPA) may be withheld, risking an opportunity to treat AIS. Although computed tomography is routinely used for tPA decision making, magnetic resonance imaging (MRI) may diagnose AIS when SM is favored but not certain. We hypothesized that a hyperacute MRI (hMRI) protocol would identify tPA-eligible AIS patients among those initially favored to have SM. METHODS: A streamlined hMRI protocol was designed based on barriers to rapid patient transport, MRI acquisition, and post-MRI tPA delivery. Neurologists were trained to order hMRI when SM was favored and tPA was being withheld. The use of hMRI for tPA decision making, door-to-needle times, and outcomes were compared before hMRI implementation (pre-hMRI: August 1, 2011 to July 31, 2013) and after (post-hMRI, August 1, 2013, to January 15, 2015). RESULTS: Post hMRI, 57 patients with suspected SM underwent hMRI (median MRI-order-to-start time, 29 minutes), of whom, 11 (19%) were diagnosed with AIS and 7 (12%) received tPA. Pre-hMRI, no tPA-treated patients were screened with hMRI. Post hMRI, 7 of 106 (6.6%) tPA-treated patients underwent hMRI to aid in decision making because of suspected SM (0% versus 6.6%; P=0.001). To ensure standard care was maintained after implementing the hMRI protocol, pre- versus post-hMRI tPA-treated cohorts were compared and did not differ: door-to-needle time (39 versus 37 minutes; P=0.63), symptomatic hemorrhage rate (4.5% versus 1.9%; P=0.32), and favorable discharge location (85% versus 89%; P=0.37). CONCLUSIONS: A streamlined hMRI protocol permitted tPA administration to a small, but significant, subset of AIS patients initially considered to have SM.

Defining the ischemic penumbra using magnetic resonance oxygen metabolic index.

BACKGROUND AND PURPOSE: Penumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel magnetic resonance imaging approach that measures oxygen metabolic index (OMI), a parameter closely related to positron emission tomography-derived cerebral metabolic rate of oxygen utilization (CMRO2), to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold that differentiates ischemic core from penumbra and (2) a reversible-injury threshold that differentiates penumbra from tissue not-at-risk for infarction. METHODS: Forty patients with acute ischemic stroke underwent magnetic resonance imaging at 3 time points after stroke onset: <4.5 hours (for OMI threshold derivation), 6 hours (to determine reperfusion status), and 1 month (for infarct probability determination). A dynamic susceptibility contrast method measured cerebral blood flow, and an asymmetrical spin echo sequence measured oxygen extraction fraction, to derive OMI (OMI=cerebral blood flow×oxygen extraction fraction). Putative ischemic threshold pairs were iteratively tested using a computation-intensive method to derive infarct probabilities in 3 tissue groups defined by the thresholds (core, penumbra, and not-at-risk tissue). An optimal threshold pair was chosen based on its ability to predict infarction in the core, reperfusion-dependent survival in the penumbra, and survival in not-at-risk tissue. The predictive abilities of the thresholds were then tested within the same cohort using a 10-fold cross-validation method. RESULTS: The optimal OMI ischemic thresholds were found to be 0.28 and 0.42 of normal values in the contralateral hemisphere. Using the 10-fold cross-validation method, median infarct probabilities were 90.6% for core, 89.7% for nonreperfused penumbra, 9.95% for reperfused penumbra, and 6.28% for not-at-risk tissue. CONCLUSIONS: OMI thresholds, derived using voxel-based, reperfusion-dependent infarct probabilities, delineated the ischemic penumbra with high predictive ability. These thresholds will require confirmation in an independent patient sample.

Accuracy of emergency medical services-reported last known normal times in patients suspected with acute stroke.

BACKGROUND AND PURPOSE: The last known normal (LKN) time is a critical determinant of IV tissue-type plasminogen activator (IV tPA) eligibility; however, the accuracy of emergency medical services (EMS)-reported LKN times is unknown. We determined the congruence between neurologist-determined and EMS-reported LKN times and identified predictors of incongruent LKN times. METHODS: We prospectively collected EMS-reported LKN times for patients brought into the emergency department with suspected acute stroke and calculated the absolute difference between the neurologist-determined and EMS-reported LKN times (|ΔLKN|). We determined the rate of inappropriate IV tPA use if EMS-reported times had been used in place of neurologist-determined times. Univariate and multivariable linear regression assessed for any predictors of prolonged |ΔLKN|. RESULTS: Of 251 patients, mean and median |ΔLKN| were 28 and 0 minutes, respectively. |ΔLKN| was <15 minutes in 91% of the entire cohort and <15 minutes in 80% of patients with a diagnosis of stroke (n=86). Of patients who received IV tPA, none would have been incorrectly excluded from IV tPA if the EMS LKN time had been used. Conversely, of patients who did not receive IV tPA, 6% would have been incorrectly included for IV tPA consideration had the EMS time been used. In patients with wake-up stroke symptoms, EMS underestimated LKN times: mean neurologist LKN time-EMS LKN time=208 minutes. The presence of wake-up stroke symptoms (P<0.0001) and older age (P=0.019) were independent predictors of prolonged |ΔLKN|. CONCLUSIONS: EMS-reported LKN times were largely congruent with neurologist-determined times. Focused EMS training regarding wake-up stroke symptoms may further improve accuracy.

Cervical arterial dissections and association with cervical manipulative therapy: a statement for healthcare professionals from the american heart association/american stroke association.

PURPOSE: Cervical artery dissections (CDs) are among the most common causes of stroke in young and middle-aged adults. The aim of this scientific statement is to review the current state of evidence on the diagnosis and management of CDs and their statistical association with cervical manipulative therapy (CMT). In some forms of CMT, a high or low amplitude thrust is applied to the cervical spine by a healthcare professional. METHODS: Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statements Oversight Committee and the American Heart Association's Manuscript Oversight Committee. Members were assigned topics relevant to their areas of expertise and reviewed appropriate literature, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge. RESULTS: Patients with CD may present with unilateral headaches, posterior cervical pain, or cerebral or retinal ischemia (transient ischemic or strokes) attributable mainly to artery-artery embolism, CD cranial nerve palsies, oculosympathetic palsy, or pulsatile tinnitus. Diagnosis of CD depends on a thorough history, physical examination, and targeted ancillary investigations. Although the role of trivial trauma is debatable, mechanical forces can lead to intimal injuries of the vertebral arteries and internal carotid arteries and result in CD. Disability levels vary among CD patients with many having good outcomes, but serious neurological sequelae can occur. No evidence-based guidelines are currently available to endorse best management strategies for CDs. Antiplatelet and anticoagulant treatments are both used for prevention of local thrombus and secondary embolism. Case-control and other articles have suggested an epidemiologic association between CD, particularly vertebral artery dissection, and CMT. It is unclear whether this is due to lack of recognition of preexisting CD in these patients or due to trauma caused by CMT. Ultrasonography, computed tomographic angiography, and magnetic resonance imaging with magnetic resonance angiography are useful in the diagnosis of CD. Follow-up neuroimaging is preferentially done with noninvasive modalities, but we suggest that no single test should be seen as the gold standard. CONCLUSIONS: CD is an important cause of ischemic stroke in young and middle-aged patients. CD is most prevalent in the upper cervical spine and can involve the internal carotid artery or vertebral artery. Although current biomechanical evidence is insufficient to establish the claim that CMT causes CD, clinical reports suggest that mechanical forces play a role in a considerable number of CDs and most population controlled studies have found an association between CMT and VAD stroke in young patients. Although the incidence of CMT-associated CD in patients who have previously received CMT is not well established, and probably low, practitioners should strongly consider the possibility of CD as a presenting symptom, and patients should be informed of the statistical association between CD and CMT prior to undergoing manipulation of the cervical spine.

Review, historical context, and clarifications of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms.

BACKGROUND AND PURPOSE: Since Food and Drug Administration approval of intravenous tissue-type plasminogen activator (tPA) for treatment of acute ischemic stroke in 1996, it has become clear that several criteria used for exclusion from therapy were not based on actual data or operationally defined for use in clinical practice. All eligibility criteria from the National Institute of Neurological Disorders and Stroke (NINDS) recombinant tPA Stroke Study were adopted within the alteplase package insert as contraindications/warnings. Many clinicians have expressed the need for clarification and better definition of these treatment criteria. METHODS: A group of investigators who also practice as stroke physicians convened a collaborative endeavor to work toward developing more clinically meaningful and consensus-driven exclusion criteria for intravenous tPA. The first of these exclusion criteria chosen was rapidly improving stroke symptoms (RISS). We reviewed and clarified the historical context and intention with the original investigators, held e-mail discussions, convened an in-person RISS Summit, and obtained the understanding of experienced stroke physicians broadly. RESULTS: Historically, the intent of this exclusion criterion within the NINDS recombinant tPA Stroke Trial was to avoid treatment of transient ischemic attacks-who would have recovered completely without treatment. There was unanimous consensus that, in the absence of other contraindications, patients who experience improvement of any degree, but have a persisting neurological deficit that is potentially disabling, should be treated with intravenous tPA. This statement is supported from the methods established for the original NINDS trial, on the basis of detailed discussions and interviews with the former NINDS trialists. It was agreed that improvement should only be monitored for the extent of time needed to prepare and administer the intravenous tPA bolus/infusion. An explicit operational definition of RISS was developed by consensus to guide future decision making in acute stroke. There was unanimous agreement that all neurological deficits present at the time of the treatment decision should be considered in the context of individual risk and benefit, as well as the patient's baseline functional status. CONCLUSIONS: A structured framework and quantitative approach toward defining RISS emerged through expert opinion and consensus. The term, RISS, should be reserved for those who improve to a mild deficit, specifically one which is perceived to be nondisabling. This is recommended to guide decision making on intravenous tPA eligibility going forward, including the design of future studies. An additional study of patients with rapid improvement to nonmild deficits is not justified because these patients should be treated.

Travel time and distance for bypass and non-bypass routing of stroke patients in the USA.

BACKGROUND: Endovascular thrombectomy is not available at all hospitals that offer intravenous thrombolysis, prompting debate regarding the preferred transport destination for acute ischemic stroke. This study aimed to quantify real-world travel time and distance of bypass and non-bypass transport models for large-vessel occlusion (LVO) and non-LVO stroke. METHODS: This cross-sectional study included population data of census tracts in the contiguous USA from the 2014-2018 United States Census Bureau's American Community Survey, stroke (thrombolysis-capable) and thrombectomy-capable centers certified by a state or national body, and road network data from a mapping service. Census tracts were categorized by urbanization level. Data were retrieved from March to November 2020. Travel times and distances were calculated for each census tract to each of the following: nearest stroke center (nearest), nearest thrombectomy-capable center (bypass), and nearest stroke center then to the nearest thrombectomy-capable center (transfer). Population-weighted median and IQR were calculated nationally and by urbanization. RESULTS: 72 538 census tracts, 2388 stroke hospitals, and 371 thrombectomy-capable centers were included. Nationally, population-weighted median travel time for nearest and bypass routing was 11.7 min (IQR 7.7-19.3) and 26.4 min (14.8-55.1), respectively. For transfer routing, the population-weighted median travel times with 60 min, 90 min, and 120 min door-in-door-out times were 94.1 min (78.5-127.7), 124.1 min (108.5-157.7), and 154.1 min (138.4-187.6), respectively. CONCLUSIONS: Bypass routing offers modest travel time benefits for LVO patients and incurs modest penalties for non-LVO patients. Differences are greatest in rural areas. A majority of Americans live in areas for which current guidelines recommend bypass.

Reducing door-to-needle times using Toyota's lean manufacturing principles and value stream analysis.

BACKGROUND AND PURPOSE: Earlier tissue-type plasminogen activator (tPA) treatment for acute ischemic stroke increases efficacy, prompting national efforts to reduce door-to-needle times. We used lean process improvement methodology to develop a streamlined intravenous tPA protocol. METHODS: In early 2011, a multidisciplinary team analyzed the steps required to treat patients with acute ischemic stroke with intravenous tPA using value stream analysis (VSA). We directly compared the tPA-treated patients in the "pre-VSA" epoch with the "post-VSA" epoch with regard to baseline characteristics, protocol metrics, and clinical outcomes. RESULTS: The VSA revealed several tPA protocol inefficiencies: routing of patients to room, then to CT, then back to the room; serial processing of workflow; and delays in waiting for laboratory results. On March 1, 2011, a new protocol incorporated changes to minimize delays: routing patients directly to head CT before the patient room, using parallel process workflow, and implementing point-of-care laboratories. In the pre and post-VSA epochs, 132 and 87 patients were treated with intravenous tPA, respectively. Compared with pre-VSA, door-to-needle times and percent of patients treated ≤60 minutes from hospital arrival were improved in the post-VSA epoch: 60 minutes versus 39 minutes (P<0.0001) and 52% versus 78% (P<0.0001), respectively, with no change in symptomatic hemorrhage rate. CONCLUSIONS: Lean process improvement methodology can expedite time-dependent stroke care without compromising safety.