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Background: The benefits of tPA (tissue-type plasminogen activator) in acute ischemic stroke are time-dependent. However, delivery of thrombolytic therapy rapidly after hospital arrival was initially occurring infrequently in hospitals in the United States, discrepant with national guidelines. Methods: We evaluated door-to-needle (DTN) times and clinical outcomes among patients with acute ischemic stroke receiving tPA before and after initiation of 2 successive nationwide quality improvement initiatives: Target: Stroke Phase I (2010–2013) and Target: Stroke Phase II (2014–2018) from 913 Get With The Guidelines-Stroke hospitals in the United States between April 2003 and September 2018. Results: Among 154 221 patients receiving tPA within 3 hours of stroke symptom onset (median age 72 years, 50.1% female), median DTN times decreased from 78 minutes (interquartile range, 60–98) preintervention, to 66 minutes (51–87) during Phase I, and 50 minutes (37–66) during Phase II ( P P P Conclusions: A nationwide quality improvement program for acute ischemic stroke was associated with substantial improvement in the timeliness of thrombolytic therapy start, increased thrombolytic treatment, and improved clinical outcomes.

Background and Purpose: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. Methods: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. Results: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38–0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37–1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27–1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. Conclusions: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01776424.

Background: Brain vascular endothelial cell (EC) dysfunction is characterized by release of pro-inflammatory mediators that contribute to atherosclerosis and ischemic stroke. Treatment with icosapent ethyl (IPE), the ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid (EPA), reduced first and total ischemic strokes each by 36%, without increasing hemorrhagic stroke, in statin-treated patients with elevated cardiovascular risk (REDUCE-IT). We tested the effects of EPA on cytokine release and expression of inflammatory proteins from brain microvascular ECs during inflammation. Methods: Human brain microvascular endothelial cells (HBECs) were pretreated with the cytokine IL-6 at 12 ng/ml for 2 h before treatment with EPA (40 μM) for 24 h. Proteomic analysis was performed using LC/MS to capture relative expression levels. Only significant changes in protein expression between treatment groups >1-fold were analyzed. Gene set enrichment analysis was also performed on all significantly regulated proteins to identify groups of proteins (pathways) that were affected. Levels of soluble intercellular adhesion molecule-1 (sICAM-1) and tumor necrosis factor-α (TNF-α) were measured by immunochemistry (ELISA). Results: IL-6 exposure produced increased levels of sICAM-1 and TNF-α by 102% and 147% (p-12 ), including heat shock protein 90-alpha and beta by 1.1-fold each relative to IL-6 alone. Conclusions: In brain vascular ECs, EPA significantly reduced expression of pro-inflammatory mediators and proteins associated with neutrophil degranulation under inflammatory conditions. The ability of EPA to reverse brain EC dysfunction during inflammatory may contribute to reductions in stroke risk.

Background: During inflammation, vascular endothelial cells (ECs) release vasoconstrictive and thrombotic factors that promote abnormal blood flow and atherothrombosis. The omega-3 fatty acid (n3FA) eicosapentaenoic acid (EPA) reduced first and total ischemic strokes each by 36% in patients with elevated cardiovascular risk (REDUCE-IT) when administered as icosapent ethyl. We measured the effects of EPA on expression of proteins involved in cytoprotection, thrombosis, and fatty acid metabolism in human brain ECs subjected to inflammation. Methods: Human brain microvascular ECs (HBECs) were first challenged with IL-6 at 12 ng/ml for 2 hr and then treated with EPA (40 μM) for 24 hr. Global proteomic analysis was performed using LC/MS to measure relative expression levels of >1,000 proteins simultaneously. Only significant (p1-fold were analyzed. Results: EPA treatment significantly modulated the expression of 504 proteins (212 increased expression, 292 decreased expression) in HBECs compared with IL-6 alone. EPA treatment increased expression of the cytoprotective enzyme heme oxygenase-1 by 1.5-fold (p = 4.7 х 10 -16 ) relative to IL-6 alone. Additionally, IL-6 increased expression of prothrombin (clotting factor II) 1.3-fold relative to control (p = 1.41 х 10 -20 ), and EPA decreased expression of prothrombin by 1.3-fold relative to IL-6 (p = 2.10 х 10 -24 ). EPA also reduced expression of fatty acid desaturase 1 & 2 by 1.4-fold and 2.6-fold, respectively, which may lead to changes in intracellular fatty acid levels. Conclusions: EPA significantly modulated expression of cytoprotective, thrombotic, and metabolic proteins in brain ECs under conditions of inflammation with IL-6. These effects of EPA on inflammation have implications for ischemic disease, including stoke, as demonstrated in large outcome trials.

Background and Purpose: Patients with prestroke mobility impairment (PSMI) were excluded from endovascular clinical trials. There are limited data regarding safety and outcomes of endovascular thrombectomy in this population. We used a large, national data set (Get With The Guidelines–Stroke) to evaluate the safety and outcomes of endovascular thrombectomy in patients with PSMI. Methods: We included patients who underwent endovascular thrombectomy in the Get With The Guidelines–Stroke registry between 2015 and 2019. PSMI was defined as the inability to ambulate independently. Generalized estimating equations for logistic regression models were used to evaluate the association between PSMI and outcomes. Results: Of 56 762 patients treated with endovascular thrombectomy, 2919 (5.14%) had PSMI. PSMI was not associated with symptomatic intracranial hemorrhage (6.0% versus 5.4%; P =0.979). In-hospital death or discharge to hospice occurred in 32.3% of patients with PSMI versus 17.5% without PSMI (adjusted odds ratio, 1.45 [1.32–1.58]). Conclusions: While procedural adverse outcomes were no higher in patients with PSMI, further study is necessary to determine clinical benefit in this population.

Background and Purpose: Many older patients presenting with acute ischemic stroke were already taking aspirin before admission. However, the management strategy for patients with aspirin treatment failure has not been fully established. Methods: We used data from the American Heart Association Get With The Guidelines Stroke Registry to describe discharge antithrombotic treatment patterns among Medicare beneficiaries with ischemic stroke who were taking aspirin before their stroke and were discharged alive from 1734 hospitals in the United States between October 2012 and December 2017. Results: Of 261 634 ischemic stroke survivors, 100 016 (38.2%) were taking aspirin monotherapy before stroke. Among them, 44.4% of patients remained on aspirin monotherapy at discharge (20.9% 81 mg, 18.2% 325 mg, 5.3% other or unknown dose). The next most common therapy choice was dual antiplatelet therapy (24.6%), followed by clopidogrel monotherapy (17.8%). The remaining 13.2% of patients were discharged on either aspirin/dipyridamole, warfarin, or nonvitamin K antagonist oral anticoagulants with or without antiplatelet, or no antithrombotic therapy at all. Conclusions: Nearly half of patients with ischemic stroke while on preventive therapy with aspirin are discharged on aspirin monotherapy without changing antithrombotic class, while the other half are discharged on clopidogrel monotherapy, dual antiplatelet therapy, or other less common agents. These findings emphasize the need for future research to identify best management strategies for this very common and complex clinical scenario.

Background and Purpose— Acute ischemic stroke patients with history of prior ischemic stroke plus concomitant diabetes mellitus (DM) were excluded from the ECASS III trial (European Cooperative Acute Stroke Study) because of safety concerns. However, there are few data on use of intravenous tissue-type plasminogen activator and symptomatic intracerebral hemorrhage or outcomes in this population. Methods— Using data from the Get With The Guidelines–Stroke Registry between February 2009 and September 2017 (n=1619 hospitals), we examined characteristics and outcomes among patients with acute ischemic stroke treated with tissue-type plasminogen activator within the 3- to 4.5-hour window who had a history of stroke plus diabetes mellitus (HxS+DM) (n=2129) versus those without either history (n=16 690). Results— Compared with patients without either history, those with both prior stroke and DM treated with tissue-type plasminogen activator after an acute ischemic stroke had a higher prevalence of cardiovascular risk factors in addition to history of stroke, DM, and more severe stroke (National Institutes of Health Stroke Scale: median, 8 [interquartile range, 5–15] versus 7 [4–13]). The unadjusted rates of symptomatic intracerebral hemorrhage and in-hospital mortality were 4.3% (HxS+DM) versus 3.8% (without either history; P =0.31) and 6.2% versus 5.5% ( P =0.20), respectively. These differences were not statistically significant after risk adjustment (symptomatic intracerebral hemorrhage: adjusted odds ratio, 0.79 [95% CI, 0.51–1.21]; P =0.28; in-hospital mortality: odds ratio, 0.77 [95% CI, 0.52–1.14]; P =0.19). Unadjusted rate of functional independence (modified Rankin Scale score, 0–2) at discharge was lower in those with HxS+DM (30.9% HxS+DM versus 44.8% without either history; P ≤0.0001), and this difference persisted after adjusting for baseline clinical factors (adjusted odds ratio, 0.76 [95% CI, 0.59–0.99]; P =0.04). Conclusions— Among patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator within the 3- to 4.5-hour window, HxS+DM was not associated with statistically significant increased symptomatic intracerebral hemorrhage or mortality risk.

Background and Purpose: Patients with pre-stroke mobility impairment were excluded from endovascular clinical trials. There is limited data regarding safety and outcomes of endovascular thrombectomy (EVT) in this population. We used a large, national dataset (Get With The Guidelines (GWTG)-Stroke) to evaluate the safety and outcomes of EVT in patients with pre-stroke mobility impairment (PSMI). Methods: We included patients who underwent EVT in the GWTG-Stroke registry between 2015 and 2019. PSMI was defined as inability to ambulate independently and poor outcome was defined as in-hospital mortality or discharge to hospice. GEE logistic regression models were used to evaluate the association between PSMI and outcomes. Results: Of 56,762 patients treated with EVT, 2919 (5.14%) had PSMI. Patients with PSMI were older (median 79 [IQR 70-87] vs 70 [59-80], P80 years and NIHSS >20 had a poor outcome. Conclusions: Amongst patients with PSMI treated with EVT, two thirds survived and one third were discharged to home or to inpatient rehabilitation. Advanced age and increased stroke severity increased the likelihood of poor outcomes. EVT appears safe in patients with PSMI, yet further study of effectiveness in this population is warranted.

Background: In patients at elevated cardiovascular risk, statins reduce the occurrence of ischemic stroke. However, residual stroke risk persists. Methods: REDUCE-IT, a multinational, double-blind trial, randomized 8179 statin-treated patients with controlled low-density lipoprotein cholesterol, elevated triglycerides, and risk for, or evidence of, atherosclerosis to icosapent ethyl (IPE), a purified, stable ethyl ester of eicosapentaenoic acid (4 grams/day), or placebo. IPE reduced the primary composite endpoint (CV death, myocardial infarction (MI), stroke, coronary revascularization, hospitalization for unstable angina) and the key secondary composite endpoint (CV death, MI, stroke) by 25% and 26%, respectively, (each ppost hoc stroke endpoints. Results: Event rates for time to first fatal or nonfatal stroke were 2.4% vs. 3.3% for IPE vs. placebo; hazard ratio (HR) (95% CI) = 0.72 (0.55-0.93); P=0.01; the relative risk reduction (RRR) was 28%, absolute risk reduction (ARR) 0.9%, and number needed to treat (NNT) 114. For every 1,000 patients treated for 5 years with IPE, approximately 14 strokes (fatal or nonfatal) were averted; rate ratio (RR) (95%CI) = 0.68 (0.52-0.91); P=0.008 (Figure). Ischemic stroke time to first event rates were 2.0% vs 3.0% for IPE vs placebo a 36% reduction [HR=0.64 (0.49-0.85); P=0.002]. Hemorrhagic stroke occurred at low rates with no significant difference for IPE vs. placebo (0.3% vs 0.2%; P=0.55). Conclusions: In REDUCE-IT, icosapent ethyl significantly reduced the risk of ischemic stroke, with no excess in hemorrhagic stroke, in statin-treated patients with elevated triglycerides and atherosclerosis or diabetes.

Introduction: Aspirin is one of the most commonly used medications for cardiovascular disease and stroke prevention. Many older patients who present with a first or recurrent stroke are already on aspirin monotherapy, yet little evidence is available to guide antithrombotic strategies for these patients. Method: Using data from the American Heart Association Get With The Guidelines-Stroke Registry, we described discharge antithrombotic treatment pattern among Medicare beneficiaries without atrial fibrillation who were discharged alive for acute ischemic stroke from 1734 hospitals in the United States between October 2012 and December 2017. Results: Of 261,634 ischemic stroke survivors, 100,016 (38.2%) were on prior aspirin monotherapy (median age 78 years; 53% women; 79.4% initial stroke and 20.6% recurrent stroke). The most common discharge antithrombotics (Figure) were 81 mg aspirin monotherapy (20.9%), 325 mg aspirin monotherapy (18.2%), clopidogrel monotherapy (17.8%), and dual antiplatelet therapy (DAPT) of 81 mg aspirin and clopidogrel (17.1%). Combined, aspirin monotherapy, clopidogrel monotherapy, and DAPT accounted for 86.8% of discharge antithrombotics. The rest of 13.2% were discharged on either aspirin/dipyridamole, warfarin or non-vitamin K antagonist oral anticoagulants with or without antiplatelet, or no antithrombotics at all. Among patients with documented stroke etiology (TOAST criteria), 81 mg aspirin monotherapy (21.2-24.0%) was the most commonly prescribed antithrombotic for secondary stroke prevention. The only exception was those with large-artery atherosclerosis, in which, 25.3% received DAPT of 81 mg aspirin and clopidogrel at discharge. Conclusion: Substantial variations exist in discharge antithrombotic therapy for secondary stroke prevention in ischemic stroke with prior aspirin failure. Future research is needed to identify best management strategies to care for this complex but common clinical scenario.

Background and Purpose— Despite quality improvement programs such as the American Heart Association/American Stroke Association Target Stroke initiative, a substantial portion of acute ischemic stroke patients are still treated with tissue-type plasminogen activator (alteplase) later than 60 minutes from arrival. This study aims to describe the documented reasons for delays and the associations between reasons for delays and patient outcomes. Methods— We analyzed the characteristics of 55 296 patients who received intravenous alteplase in 1422 hospitals participating in Get With The Guidelines-Stroke from October 2012 to April 2015, excluding transferred patients and inpatient strokes. We assessed eligibility, medical, and hospital reasons for delays in door-to-needle time. Results— There were 27 778 patients (50.2%) treated within 60 minutes, 10 086 patients (18.2%) treated >60 minutes without documented delays, and 17 432 patients (31.5%) treated >60 minutes with one or more documented reasons for delay. Delayed door-to-needle times were associated with delayed diagnosis (36 minutes longer than those without delay in diagnosis) and hypoglycemia or seizure (34 minutes longer than without those conditions). The presence of documented delays was associated with higher odds of in-hospital mortality (odds ratio, 1.2; 95% confidence interval, 1.1–1.3) and symptomatic intracranial hemorrhage (odds ratio, 1.2; 95% confidence interval, 1.1–1.3) and lower odds of independent ambulation at discharge (odds ratio, 0.92; 95% confidence interval, 0.9–1.0) after adjusting for patient and hospital characteristics. Conclusions— Hospital and eligibility delays such as delay diagnosis and inability to determine eligibility were associated with longer door-to-needle times. Improved stroke recognition and management of acute comorbidities may help to reduce door-to-needle times.

Introduction: A significant proportion of acute ischemic strokes occur while patients are hospitalized for other reasons. Limited data exist on the utilization of intravenous alteplase (IV tPA) for in-hospital stroke, particularly in the endovascular era. We compared temporal trends of IV tPA use, patient characteristics, process measures of quality, and outcomes for in-hospital versus community onset strokes in a national registry. Methods: We performed a retrospective cohort study of Get With The Guidelines-Stroke (GTWG-Stroke) from January 2008 to June 2018 from 2,333 participating sites that included 2,428,178 patients with acute ischemic stroke. In-hospital onset was reported in 67,493 patients. We examined the association between stroke onset location, patient characteristics, comorbidities, treatment with IV tPA and unadjusted and adjusted functional outcomes (Table, standardized differences >10% for significance). Results: Of 67,493 patients with in-hospital onset stroke, 11,123 received IV tPA. The rate of IV tPA administration steadily increased, from 9.5% in 2008 to 20.7% in 2017 (p Conclusions: In this national cohort, in-hospital onset strokes are increasingly treated with intravenous tPA in a period that spans the endovascular era. Compared with community-onset stroke, patients with in-hospital onset stroke had longer intervals to thrombolysis and worse outcomes. These data highlight opportunities to improve inpatient systems of stroke care further.

Introduction: A significant number of acute ischemic strokes occur while patients are hospitalized for other reasons. No national data have been reported on endovascular therapy (EVT) for in-hospital onset stroke. Here we compare the patient characteristics, process measures of quality, and outcomes for in-hospital onset vs. community-onset of strokes in a large US national registry. Methods: We performed a retrospective cohort study of Get With The Guidelines-Stroke (GTWG-Stroke) from January 2008 to June 2018 from 2,333 participating sites that included 2,428,178 patients with acute ischemic stroke. Among 67,493 in-hospital onset strokes, 2494 (3.7%) underwent EVT. We examined the association between key patient characteristics (in-hospital onset, demographics, comorbidities, treatment with EVT) and functional outcomes using multivariable logistic regression models. Results: The rate of EVT increased from 2.5% in 2008 to 6.4% in 2018 (p Conclusions: Though use of EVT in GWTG-Stroke for in-hospital stroke remains low, it more than doubled in the past decade. Compared with community onset stroke, these patients have longer intervals to CT and arterial puncture, with associated worse functional outcomes. While there may be important differences in baseline patient characteristics between the groups, efforts must still be made to shorten time to reperfusion for in-hospital strokes.

Introduction: Lifelong aspirin therapy is recommended after a TIA or stroke, but dyspeptic symptoms frequently lead to non-adherence. Clinicians often recommend that daily doses be taken with food to reduce these side effects. However, food can interfere with absorption, especially with enteric coated aspirin tablets. Hypothesis: We evaluated whether food interferes with bioavailability of a new, pharmaceutical lipid-aspirin complex (PL-ASA) liquid-filled capsule formulation. Methods: This was a randomized, open label, crossover study in 20 healthy volunteers. Participants fasted for ≥10 hours prior to randomization; if assigned to “fasting” they then received the single 650 mg dose of PL-ASA. If they were randomized to “fed”, they first ate a standard high-fat meal and were dosed 30 minutes later. After a washout period of 10 days each participant crossed over to the other arm and was again dosed with a 650 mg dose of PL-ASA. The primary outcome was the comparison of PK parameters of the primary metabolite salicylic acid (SA) between fasting and fed states. Results: Mean age of participants was 36.8 years and 55% were male. The primary SA PK parameters of AUC 0-t and AUC 0- infinity in the fed state were within 88.7% and 88.8% of concentrations in the fasting state consistent with bio-equivalence (FDA guidance >80%). Mean peak SA concentration was about 25% lower and occurred about 1.5 hours later in the fed state (Figure). Conclusions: Food had a modest effect on the time required to reach peak SA concentration and on the actual peak SA levels after PL-ASA administration, but did not impact the extent of exposure (area under the curve) compared with intake in a fasting state. These data demonstrate that PL-ASA may be co-administered with food without significant variability in absorption, a recognized limitation of coated aspirin formulations.

Background and Purpose— Primary stroke center (PSC) certification was established to identify hospitals providing evidence-based care for stroke patients. The numbers of PSCs certified by Joint Commission (JC), Healthcare Facilities Accreditation Program, Det Norske Veritas, and State-based agencies have significantly increased in the past decade. This study aimed to evaluate whether PSCs certified by different organizations have similar quality of care and in-hospital outcomes. Methods— The study population consisted of acute ischemic stroke patients who were admitted to PSCs participating in Get With The Guidelines-Stroke between January 1, 2010, and December 31, 2012. Measures of care quality and outcomes were compared among the 4 different PSC certifications. Results— A total of 477 297 acute ischemic stroke admissions were identified from 977 certified PSCs (73.8% JC, 3.7% Det Norske Veritas, 1.2% Healthcare Facilities Accreditation Program, and 21.3% State-based). Composite care quality was generally similar among the 4 groups of hospitals, although State-based PSCs underperformed JC PSCs in a few key measures, including intravenous tissue-type plasminogen activator use. The rates of tissue-type plasminogen activator use were higher in JC and Det Norske Veritas (9.0% and 9.8%) and lower in State and Healthcare Facilities Accreditation Program certified hospitals (7.1% and 5.9%) ( P Conclusions— Among Get With The Guidelines-Stroke hospitals with PSC certification, acute ischemic stroke quality of care and outcomes may differ according to which organization provided certification. These findings may have important implications for further improving systems of care.

Background and Purpose— Antithrombotics are the mainstay of treatment in primary and secondary prevention of stroke, and their use before an acute event may be associated with better outcomes. Methods— Using data from Get With The Guidelines-Stroke with over half a million acute ischemic strokes recorded between October 2011 and March 2014 (n=540 993) from 1661 hospitals across the United States, we examined the unadjusted and adjusted associations between previous antithrombotic use and clinical outcomes. Results— There were 250 104 (46%) stroke patients not receiving any antithrombotic before stroke; of whom approximately one third had a documented previous vascular indication. After controlling for clinical and hospital factors, patients who were receiving antithrombotics before stroke had better outcomes than those who did not, regardless of whether a previous vascular indication was present or not: adjusted odds ratio (95% confidence intervals) were 0.82 (0.80–0.84) for in-hospital mortality, 1.18 (1.16–1.19) for home as the discharge destination, 1.15 (1.13–1.16) for independent ambulatory status at discharge, and 1.15 (1.12–1.17) for discharge modified Rankin Scale score of 0 or 1. Conclusions— Previous antithrombotic therapy was independently associated with improved clinical outcomes after acute ischemic stroke. Ensuring the use of antithrombotics in appropriate patient populations may be associated with benefits beyond stroke prevention.

Introduction: Many patients with ischemic stroke do not receive tissue plasminogen activator (tPA) due to late arrival to the hospital. We assessed whether socioeconomic status (SES) and home-to-hospital driving-times impact tPA administration and timeliness of treatment, and evaluated the interaction between SES and driving time. Methods: We conducted a retrospective observational study using data collected from Get With The Guidelines-Stroke between January 2015 to March 2017. The study included 118,683 ischemic stroke patients age ≥18 from 1,489 US hospitals across the US. All patients arrived via EMS from a non-healthcare facility within 24 hours of symptom onset. We estimated patient SES using zip code median household income, and calculated the driving time between each patient’s home zip code and the hospital where they were treated, using the Google Maps Directions Application Programing Interface. The primary outcomes were tPA administration and onset-to-arrival time (OTA), analyzed using hierarchical multivariable logistic regression models with random intercepts to account for clustering at the hospital level. Results: Patients had a median OTA of 155 minutes (64-484) and 26.5% were treated with tPA. Zip code median income quintiles were $46,400, $52,136, $57,895 and $70,150. Driving time quartiles were 13.5, 20.7 and 32.1 minutes. SES was not significantly associated with tPA administration (p=0.47) or OTA (p=0.31). However, lower SES was associated with longer symptom onset to treatment time (p=0.02) and higher in-hospital mortality (p=0.004). Longer driving time (comparing top to bottom quartile) was associated with a lower rate of tPA administration (OR 0.83, 0.79-0.88, p Conclusions: Longer home-to-hospital driving times were associated with lower rates of tPA and longer OTA, however SES did not modify these associations.

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= 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.

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.

Introduction: Direct oral anticoagulants (DOACs) are increasingly used as alternatives to warfarin for secondary prevention in ischemic stroke patients with atrial fibrillation. Despite demonstrated efficacy in clinical trials, there are few real-world experiences of DOACs vs. warfarin in community practice. Methods: We analyzed ischemic stroke survivors with atrial fibrillation discharged from the Get With The Guidelines Stroke hospitals between 2011-2014 and linked to Medicare claims for longitudinal outcomes through 2015. A propensity score overlap weighting method was used to compare DOACs vs. warfarin. The primary outcomes were major adverse cardiovascular events (MACE) and home time, a patient-centered outcome reflecting desire of “being alive at home, without recurrent stroke, or being hospitalized for complications.” Results: Among 11,662 stroke survivors (median age 80), 4,041 (34.7%) were discharged on DOACs (dabigatran, rivaroxaban, or apixaban) and 7,621 on warfarin. Except for NIHSS (median 4 [IQR 1-9] vs. 5 [2-11]), baseline demographics, medical history, and clinical characteristics were similar between two cohorts. Compared with warfarin, patients discharged on DOACs were less likely to experience MACE (33.95% vs. 40.36% per year, adjusted hazard ratio 0.89, 99% CI 0.83-0.96) and had more days at home (mean 287 vs. 263 days during the first year post discharge, adjusted difference 15.6 days, 99% CI 9.0-22.1) ( Table ). Additionally, there were fewer deaths, all-cause readmissions, cardiovascular readmissions, hemorrhagic strokes, and bleeding hospitalizations in DOAC-treated patients, although no significant differences in fatal bleeding, ischemic stroke readmission, systemic embolism, pneumonia, or sepsis (two negative outcome controls) between the two cohorts. Conclusions: In ischemic stroke survivors with atrial fibrillation, DOACs were associated with improved long-term clinical outcomes compared with warfarin.

Background: Treatment with intravenous recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke (AIS) in patients with a recent history of myocardial infarction (MI) within 3 months prior to AIS is controversial. Methods: We used probabilistic linkage of Medicare claim files with the Get With The Guidelines-Stroke registry to identify patients who were treated with rtPA for AIS between 2/2009 and 12/2015. Recent MI was determined from Medicare claims. Multivariable logistic regression models were used to evaluate the association of a recent history of MI with in-hospital clinical outcomes. Results: Among 40,396 patients age 65 years or older treated with rtPA for AIS from 1522 sites (mean age [SD] 81.0 [8.1] years; 58.0% women), 241 (0.6%) had recent MI within 3 months prior to AIS, of which 19.5% were STEMI. Patients with recent MI had more severe stroke than those without (median NIHSS [IQR]: 13.0 [7.0-20.0] vs. 11.0 [6.0-18.0]) and were more likely to be on antiplatelets prior to AIS (87.8% vs. 53.6%). The unadjusted rates of in-hospital mortality and any serious rtPA-related complications were 17.4% and 13.5% for those with recent MI, and 9.0% and 9.4% for those without, respectively. Hemopericardium was observed in 1 (0.4%) patient with recent MI. After risk adjustment, recent MI within 3 months was associated with a significant increased risk of mortality (adjusted odds ratio [OR] 1.61, 95%CI [1.11-2.34], P=0.012), whereas there were no statistically significant differences in any serious rtPA-related complications ( Table ). When stratified by the type of MI, recent ST-elevation MI was associated with higher risk of death and tPA complications, but the difference was not statistically significant in those with recent non ST-elevation MI. Conclusions: Among older ischemic stroke patients treated with rtPA, recent MI within 3 months was associated with an increased risk of mortality, and recent STEMI with mortality and serious tPA complications.

Background and Purpose: Adherence to evidence-based guidelines is an important indicator of hospital stroke care quality; yet, there is lack of assessment of patient characteristics and performance measures in acute ischemic stroke for most world regions. Methods: We analyzed data of 19,604 acute ischemic stroke patients in China National Stroke Registry and 194,876 patients in GWTG-Stroke registry in US between 2012 to 2013 and compare their baseline characteristics and hospital performance measures. Results: Compared with US, Chinese patients were younger and had lower prevalence of comorbidities except for history of stroke/TIA or smoking. NIHSS was similar (China vs. US: median 4 [IQR 2-7] vs. 4 [1-10]). Chinese patients were more likely to have delays from last-known-well to hospital arrival (median 1,318 minutes [330-3,209] vs. 644 [142-2,055]), less likely to receive thrombolytic therapy (2.5% vs. 8.1%), and were more likely to experience treatment delays (door-to-needle time 95 minutes [72-112] vs. 62 [49-85]). Adherence to early and discharge antithrombotics, smoking cessation counseling, and dysphagia screening were relatively high (e.g.>80%) in both countries. However, large gaps existed in administration of intravenous thrombolytics within 3 hours (18.3% vs. 83.6%), door-to-needle time ≤60 minutes (14.6% vs. 48.0%), deep vein thrombosis prophylaxis (65.0% vs. 97.8%), anticoagulation for atrial fibrillation (21.0% vs. 94.4%), lipid treatment for low-density lipoprotein > 100 mg/dL (66.3% vs. 95.8%), and rehabilitation assessment (58.8% vs. 97.4%). Door-to-CT ≤25 minutes was relatively low in both countries (26.4% vs. 27.9%). Conclusions: We found significant differences in clinical characteristics and gaps in adherence for certain performance measures between China and US. Additional efforts are needed for continued improvements in acute stroke care and secondary prevention in both nations, especially China.

Background and Purpose— Although there are no trials or large cohorts to inform clinical care, current guidelines caution against giving intravenous tPA (tissue-type plasminogen activator) to patients with acute ischemic stroke who are taking non–vitamin K antagonist oral anticoagulants (NOACs). We performed a literature review of intravenous tPA in patients treated with NOACs preceding stroke. Methods— A literature search of PubMed was performed encompassing January 2010 to March 2018. Patient characteristics, timing of last medication intake, laboratory testing, use of reversal, and outcomes ≤3 months after discharge were summarized. Results— We identified 55 studies with 492 NOAC patients receiving tPA (dabigatran, 181; rivaroxaban, 215; apixaban, 40; and unspecified NOAC, 56). Among patients with complete data, the median time from the last NOAC intake to symptom onset was 8 hours (interquartile range, 2.5–14.5), with 55.2% (80/145) within 12 hours. Few patients underwent sensitive laboratory tests, such as thrombin time, diluted thrombin time, or anti-Xa assays before tPA administration. The overall observed rates of symptomatic intracranial hemorrhage, mortality, and favorable outcomes (National Institutes of Health Stroke Scale score, ≤1; modified Rankin Scale score, 0–2; or neurological improvement in the National Institutes of Health Stroke Scale score, ≥8 points) were 4.3% (20/462), 11.3% (48/423), and 43.7% (164/375), respectively. Among dabigatran-treated patients, reversal with idarucizumab was associated with fewer symptomatic intracranial hemorrhage (4.5% [2/44] versus 7.4% [8/108]; unadjusted odds ratio, 0.60; 95% CI, 0.12–2.92), death (4.5% [2/44] versus 12.0% [13/108]; unadjusted odds ratio, 0.35; 95% CI, 0.08–1.61), and more favorable outcomes (79.1% [34/43] versus 39.2% [29/74]; unadjusted odds ratio, 5.86; 95% CI, 2.45–14.00), although the differences were not statistically significant for symptomatic intracranial hemorrhage and death. Conclusions— These preliminary observations suggest that tPA may be reasonably well tolerated without prohibitive risks of bleeding complications in selected patients on NOACs. Reversal of anticoagulant effects by idarucizumab for dabigatran-treated patients before tPA is an emerging strategy that was associated with more favorable outcomes.

Background: We sought to examine the longitudinal outcomes following admission for transient ischemic attack (TIA) among Medicare beneficiaries admitted at GWTG-Stroke participating hospitals and to examine this varies by ABCD 2 score categories. Methods: We identified TIA hospitalizations from GWTG-Stroke and linked these with Medicare claims for January 1, 2011 to December 31, 2014 to determine 1-year event rates of mortality, all-cause hospital readmission, composite outcome of mortality and all-cause readmission, and readmissions related to ischemic stroke (IS) and major vascular events. Patients were identified as high risk (ABCD 2 score ≥ 4) or low risk (ABCD 2 score 0-3) to assess differences in outcomes by risk group. Results: Of 394,920 patients from 1,779 hospitals with IS/TIA, 77,819 (19.7%) had a diagnosis of TIA at hospital discharge. Mean age was 80 years and 39.4% were male. Outcomes at 1-year included mortality in 11.9%, all-cause readmission 44.2%, composite of mortality/all-cause readmission 47.1%, ischemic stroke related admission 3.5%, and readmission related to major vascular events 5.3%. Of the 40,825 patients with complete data to calculate an ABCD 2 score, 86% were high risk (n=35,118) and 14% low risk (n= 5,707). There was a significant difference between these two groups in adjusted risk for 1-year outcomes of mortality, mortality/all-cause readmission and ischemic stroke admission but not major vascular readmission (Table 1). Conclusions: There was a high rate of adverse events including mortality and ischemic stroke admission, among Medicare beneficiaries admitted with TIA at GWTG-Stroke participating hospitals. The ABCD 2 score identified TIA patients at higher risk of adverse outcomes.

Introduction: Though overall stroke incidence and mortality in U.S. is improving, little is known about the state of stroke care and trends over time in Asian-Americans. Methods: We abstracted clinical characteristics, treatment patterns, and outcomes from acute ischemic stroke admissions for Asian-American and White patients from 4/1/04-7/31/16 from 2,171 hospitals in Get With The Guidelines-Stroke. Multivariable regression models assessed association of Asian ethnicity and outcomes that adjusted for patient and hospital characteristics and NIHSS. Results: Study population (N=1,772,299) had 64,337 Asian-American patients (3.6%) and 1,707,962 White patients; mean age 72.4, 51.3% female. Asians had greater stroke severity than Whites (Table). After adjustment, Asians had greater stroke severity, higher in-hospital mortality, poorer functional recovery, received IVtPA less but had more serious and hemorrhagic complications, despite being more likely to receive IV tPA Conclusions: This is the largest analysis of clinical and functional outcomes for Asian-American acute ischemic stroke patients. Asian-Americans have more severe ischemic strokes, worse functional outcomes, and receive less IVtPA than White patients. These findings warrant additional research, and more dedicated interventions towards improving clinical outcomes for Asian-American patients with acute ischemic stroke.

Background: Antidepressant (AD) therapy has been shown to improve post-stroke depressive symptoms, yet few data are available on characteristics associated with treatment at the time of discharge after ischemic stroke. Methods: PROSPER is a PCORI-funded study designed by researchers and stroke survivors to evaluate the effectiveness of therapies post-stroke. We used information from ischemic stroke patients discharged from April 2014 - December 2014 in the American Heart Association’s Get With The Guidelines (GWTG)-Stroke registry who were linked to Centers for Medicare and Medicaid Services (CMS) data to evaluate antidepressant medication use following hospitalization for ischemic stroke. Results: Of 29,177 eligible patients from 1,023 hospitals, n=7,593 (26.0%) were prescribed AD at hospital discharge. The majority of discharge AD prescriptions were for an SSRI (70.6%) and in patients with history of depression and on AD prior to admission. Patients discharged on an AD were more likely to be female, of white race, and to have a prior history of cardiovascular diseases (Table). Discharge AD prescription was more common at teaching hospitals, hospitals with larger bed size and higher annual volume of ischemic stroke admissions. Amongst the patients who were not on AD prior to admission (22,437), only 8.1% were discharged on AD. Patients discharged on AD amongst AD naïve population were more likely to be female, of white race, had prior history of depression, had higher initial NIHSS and more likely to be discharged to a facility. Conclusions: Among CMS linked patients, antidepressant prescription after ischemic stroke is low and varies by key patient and hospital level characteristics. Future research examining the association between discharge AD use and patient reported outcomes after stroke is needed.

Background: To improve stroke care, the Brain Attack Coalition recommended establishing primary stroke center (PSC) and comprehensive stroke center (CSC) certification. Achieving CSC designation requires the ability to provide more complex services. However, it remains unknown whether CSCs have better performance than PSCs for ischemic stroke care. This study compared ischemic stroke care between CSCs and PSCs. Methods: The study included consecutive patients who were admitted to the 134 CSCs and 1047 PSCs participating in Get With The Guidelines (GWTG)-Stroke between January 1, 2013 and December 31, 2015 with a final diagnosis of acute ischemic stroke. Multivariable logistic regression models were generated to examine the association between stroke center certification (CSC vs PSC) and performance measures and outcomes, after adjusting for potential confounders including patient and hospital characteristics. Results: Of the 605,136 patients who were admitted directly from the emergency department, 110,624 were admitted to CSCs and 494,512 to PSCs. CSCs were larger than PSCs (median number of beds 481 vs 263). Performance differences between CSCs vs. PSCs are shown in the table. CSCs and PSCs had comparable overall conformity to the seven performance measures represented by the summary defect-free care measure. CSCs outperformed PSCs in several key measures, especially the use of intravenous tissue plasminogen activator (IV tPA) and intra-arterial thrombectomy (IA-therapy). Compared with patients at PSCs, patients at CSCs were more likely to receive IV tPA in both unadjusted and adjusted models. The door to IV tPA time was shorter at CSCs. Patients at CSCs were more likely to receive IA therapy, with shorter door to IA therapy times. Mortality was higher at CSCs. Conclusions: Stroke care at CSCs exceeded PSCs for many but not all quality measures, particularly timely acute reperfusion therapy. Risk adjusted in-hospital mortality was modestly higher at CSCs.

Background: The impact of the preceding use of concomitant use of antiplatelet and anticoagulation therapies on outcomes of intracerebral hemorrhage (ICH) has not been thoroughly investigated. Methods: We analyzed 138,834 patients presenting with ICH between October 2013 and December 2016 from 1661 hospitals participating in the Get With The Guidelines-Stroke program. Multivariable logistic regression was used to evaluate the impact of concomitant antiplatelet therapy on in-hospital mortality in anticoagulation-related ICH. Results: Of 138,834 patients (mean [SD] age 68.4 [15.3] years; 48.0% women), 118,219 (85.2%) patients were not receiving any oral anticoagulant (OAC), 15,777 (11.4%) were receiving warfarin and 4,838 (3.5%) were receiving non-vitamin K oral anticoagulants (NOACs) prior to ICH. Stroke severity as measured by NIHSS was similar across three groups. Patients receiving warfarin or NOACs were more likely to have single antiplatelet therapy (SAPT) than those receiving no OAC (33.0% for warfarin, 30.7% for NOACs, and 27.3% for no OAC), whereas patients receiving no OAC were more likely to have dual antiplatelet therapy (DAPT) (2.5% for warfarin, 2.3% for NOACs, and 4.4% for no OAC). After adjustment for confounders, SAPT was associated with a slightly higher rate of mortality (33.8% vs. 32.1%, adjusted odds ratio [AOR] = 1.20, 95% CI [1.11-1.30]) than no antiplatelet in patients receiving warfarin, whereas there were no statistically significant differences between SAPT vs. no antiplatelet in patients with no OAC (22.4% vs. 22.9%, AOR = 0.99 [0.95-1.03]) or NOACs (26.8% vs. 26.9%, AOR = 1.09 [0.94-1.26]). DAPT was associated with increased risk of death in patients taking warfarin (46.5% vs. 32.1%, AOR = 2.08 [95% CI, 1.68-2.57]) and no OAC (30.4% vs. 22.9%, AOR = 1.51 [95% CI, 1.40-1.63]). By contrast, in patients taking NOACs, the association of DAPT was not significant but the confidence intervals were wider (32.7% vs. 26.9%, AOR = 1.37 [95% CI, 0.90-2.08]) likely due to small sample size. Conclusions: In patients experienced an ICH, prior concomitant use of antiplatelet therapy (either SAPT or DAPT) significantly increased odds of mortality in patients taking warfarin, but such a difference was not apparent in NOAC-treated ICH patients.

Background and Purpose— Although racial/ethnic differences in care are pervasive in many areas of medicine, little is known whether intracerebral hemorrhage (ICH) care processes or outcomes differ by race/ethnicity. Methods— We analyzed 123 623 patients with ICH (83 216 white, 22 147 black, 10 519 Hispanic, and 7741 Asian) hospitalized at 1199 Get With The Guidelines-Stroke hospitals between 2003 and 2012. Multivariable logistic regression with generalized estimating equation was used to evaluate the association among race, stroke performance measures, and in-hospital outcomes. Results— Relative to white patients, black, Hispanic, and Asian patients were significantly younger, but more frequently had more severe stroke (median National Institutes of Health Stroke Scale, 9, 10, 10, and 11, respectively; P Conclusions— Although individual quality indicators in ICH varied by race/ethnicity, black, Hispanic, and Asian patients with ICH had lower risk-adjusted in-hospital mortality than white patients with ICH.

Background and Purpose— The benefits of intravenous tissue-type plasminogen activator in acute ischemic stroke are time dependent, and several strategies have been reported to be associated with more rapid door-to-needle (DTN) times. However, the extent to which hospitals are using these strategies and their association with DTN times have not been well studied. Methods— We surveyed 304 Get With The Guidelines-Stroke hospitals joining Target: Stroke regarding their baseline use of strategies to reduce DTN times in the January 2008 to December 2009 time frame before the initiation of Target: Stroke and determined the association between hospital strategies and DTN times. Results— Among 5460 patients receiving tissue-type plasminogen activator within 3 hours of symptom onset in surveyed hospitals, the median DTN time was 72 minutes (interquartile range, 55–94). Reported use of the different strategies varied considerably. Of 11 hospital strategies analyzed individually by multivariable analysis, 3 strategies were independently associated with shorter DTN times. These included rapid triage/stroke team notification (209/304 [69%] hospitals, 8.1-minute reduction in DTN time), single-call activation system (190/304 [63%] hospitals, 4.3 minutes), and tissue-type plasminogen activator stored in the emergency department (189/304 [62%] hospitals, 3.5 minutes). When analyzed incrementally, hospitals that used a greater number of strategies had shorter DTN times with 1.3 minutes (adjusted mean difference) saved for each strategy implemented (14 minutes if all strategies were used). Conclusions— Although the majority of participating hospitals reported using some strategy to reduce delays in tissue-type plasminogen activator administration for acute ischemic stroke, the strategies applied vary considerably and those most strongly associated with shorter DTN times were applied relatively less frequently.

Background and Purpose— Analysis of quality of care for in-hospital stroke has not been previously performed at the national level. This study compares patient characteristics, process measures of quality, and outcomes for in-hospital strokes with those for community-onset strokes in a national cohort. Methods— We performed a retrospective cohort study of the Get With The Guidelines-Stroke (GWTG-Stroke) database of The American Heart Association from January 2006 to April 2012, using data from 1280 sites that reported ≥1 in-hospital stroke. Patient characteristics, comorbid illnesses, medications, quality of care measures, and outcomes were analyzed for 21 349 in-hospital ischemic strokes compared with 928 885 community-onset ischemic strokes. Results— Patients with in-hospital stroke had more thromboembolic risk factors, including atrial fibrillation, prosthetic heart valves, carotid stenosis, and heart failure ( P P P Conclusions— Compared with community-onset ischemic stroke, patients with in-hospital stroke experienced more severe strokes, received lower adherence to process-based quality measures, and had worse outcomes. These findings suggest there is an important opportunity for targeted quality improvement efforts for patients with in-hospital stroke.

Background: Intravenous recombinant tissue-type plasminogen activator (rt-PA) administration improves outcomes in acute ischemic stroke. However, young patients ( Methods: We analyzed data from the large national Get With The Guidelines–Stroke registry for acute ischemic stroke patients hospitalized between January 2009 and September 2015. Multivariable models with generalized estimating equations (GEE) were used to test for differences between younger (age 18-40) and older (age > 40) acute ischemic stroke patients, controlling for patient and hospital characteristics including stroke severity. Results: Of 1,320,965 AIS patients admitted to participating hospitals, 2.3% (30,448) were aged 18-40. Among these patients, 12.5% received rt-PA versus 8.8% of those aged >40 (p Conclusions: Young acute ischemic stroke patients did not receive rt-PA treatment at lower rates than older patients. Outcomes were better and the rate of symptomatic intracranial hemorrhage was lower in the young patients. However, younger patients had significantly longer door-to-CT and DTN times, providing an opportunity to improve the care of these patients.

Introduction: Relationship of prior glycemic status to outcomes in intracerebral hemorrhage (ICH) is not established. Hypothesis: Higher hemoglobin (Hb) A1c is associated with worse outcomes in ICH. Methods: Data harvested from GWTG-Stroke registry on patients with ICH between April 1, 2003 and September 30, 2015. Four ordinal groups made based on HbA1c values of 8.0%. Outcomes analyzed overall and separately for patients with or without history of diabetes using unadjusted and adjusted multivariable regression models. Results: Among 75,455 patients with ICH from 1,336 sites, the prevalence of diabetes was 36.2% and prediabetes (no prior history of diabetes and HbA1c between 5.7-6.4%) was 41.9%. An increasing trend in the median BMI values was noted across the groups, with worse HbA1c associated with higher BMI. Lower HbA1c was associated with higher in-hospital mortality (3947/25473 {15.5%} overall, 542/2852 {19.0%} in patients with history of diabetes, and 3405/22621{15.1%} in patients without history of diabetes) (Table), higher mRS, less chance of going home, and lower likelihood of having independent ambulatory status, also seen in unadjusted and adjusted outcomes (Figure). Only in patients with no prior diabetes history, both higher HbA1c and lower HBA1c were associated with higher in-hospital mortality. Conclusions: In this large cohort of ICH patients, contrary to our original hypothesis, lower HbA1c (rather than higher HbA1c) was associated with higher in-hospital mortality. Further studies are needed to better define the relationship between HbA1c and outcomes, for it may have important implications for care of ICH patients.

Introduction: Use of anti-platelet therapy is common among patients presenting with intracerebral hemorrhage (ICH). There are limited data regarding pre-stroke antiplatelet therapy (APT) and outcomes in patients presenting with spontaneous ICH. We hypothesized that prior use of antiplatelet agents increases mortality and discharge morbidity in ICH patients. Methods: We analyzed data of 82,576 ICH patients not on anticoagulation from 2185 GWTG-Stroke hospitals between Oct 2012 and March 2016. Patients were categorized as no APT, single antiplatelet therapy (SAPT) and dual antiplatelet therapy (DAPT). Logistic regression using generalized estimating equations to account for within-site correlations were used to assess the relationship between outcomes and prior-APT use. Results: No pre-ICH APT was used in 65.8%, SAPT in 29.5%, and DAPT in 4.8%. The median age of the cohort was 69 years and prevalence of females in the cohort was 48.6%, with preponderance of white race (58.9%). Overall onset of symptoms to arrival time was 131 minutes with a median NIHSS of 9. A total of 23.7% had history of previous stroke/transient ischemic attack, 15.3% had prior myocardial infarction/coronary artery disease and 73.4% had known hypertension. There was no significant difference in in-hospital mortality among patients not on any APT vs patients on SAPT. However, in-hospital mortality was higher among ICH patients on DAPT compared with no therapy (adjusted OR 1.41, 95 % CI 1.31-1.51, P Conclusion: Our study suggests that patients on DAPT, but not on SAPT, have higher mortality rates after ICH compared with patients on no APT.

Background: Despite quality improvement programs such as the American Heart Association/American Stroke Association Target_Stroke initiative, a substantial portion of acute ischemic stroke patients are still treated with alteplase later than 60 minutes, for unclear reasons. This study aims to describe the documented reasons for delays as well as the associations between reasons for delays and patient outcomes. Methods: We analyzed 55,296 patients who received intravenous alteplase in 1,422 hospitals participating in Get With The Guidelines-Stroke from October 2012 to April 2015, excluding transferred patients and inpatient strokes. We assessed eligibility, medical, and hospital reasons for delays in door-to-needle time (DTN). Multivariable models were used to evaluate associations between reasons for delays, time lost, and hospital discharge outcomes, controlling for patient and hospital characteristics. Results: There were 27,778 (50.2%) patients treated within 60 minutes, 10,086 (18.2%) treated in more than 60 minutes without documented delays, and 17,432 (31.5%) treated in more than 60 minutes with one or more documented reasons for delay. The longest DTN times were associated with inability to determine eligibility, delay in diagnosis, further diagnostic evaluation for hypoglycemia or seizure, management of emergent medical conditions and initial patient refusal (Table). One or more reason for delays was associated with in-hospital mortality (OR 1.2; 95CI 1.1-1.3), symptomatic intracranial hemorrhage (OR 1.2; 95CI 1.1-1.3), and lower odds of independent ambulation at discharge (OR 0.92; 95CI 0.9-1.0). Conclusions: Hospital and eligibility delays such as delay in diagnosis and inability to determine eligibility are common and are associated with longer DTN and poorer outcomes. Improved stroke recognition and management of acute comorbidities may help to reduce DTN times and improve outcomes.

Background and Purpose: Endovascular thrombectomy (EVT) is now standard of care in eligible patients with acute disabling ischemic stroke, and is more effective when delivered quickly. It is currently unclear whether time targets achieved in clinical trials can also be achieved in routine clinical practice. Here, we describe interval times from stroke onset to patient arrival in emergency room (door) to first pass/initiation of treatment in patients receiving EVT within Get With The Guidelines-Stroke hospitals (GWTG-S). Methods: Data are from sites participating fully as Comprehensive Stroke Centers within GWTG-S from 8/2014-3/2016. Analyzed work flow times include stroke onset to door , door to imaging, imaging to arterial access, arterial access to first pass time (defined as the earliest of either deployment of a mechanical reperfusion device or intra-arterial alteplase initiated) and the composite door-to-first-pass time. Data are described overall and analyzed by calendar year quarters. Trends are tested using the Cochran-Mantel-Haenszel test. Results: Data are reported from 1891 patients from 172 hospitals. Median time from stroke onset to door was 77 mins (IQR 46-144 min), imaging to arterial access was 91 min (64-126 min), and arterial access to first pass time was 18 min (4-31 min) (Figure). Median door-to-first-pass time was 129 min (IQR 97-171 min). Only 5.3% had a door-to-first-pass time Conclusion: Although workflow is improving, efforts need to continue on streamlining workflow and saving time so that the true potential of EVT is realized. These data may inform benchmark goals for EVT workflow times.

Background: The benefits of intravenous tPA in acute ischemic stroke are time-dependent and hospitals participating in Target: Stroke have substantially improved the proportion of patients being treated with door-to-needle (DTN) times of ≤60 minutes. However, very few patients were treated with DTN times of ≤45 or ≤30 minutes during Target: Stroke Phase I (2010-2013). This study aims to assess whether there have been greater achievement of DTN times ≤45 and ≤30 minutes since the launch of Target: Stroke Phase II in Q2 2014. Methods: Target: Stroke Phase II identified and disseminated additional best practice strategies, provided updated clinical decision support tools, and set new hospital recognition goals. Rates of DTN times ≤45 and ≤30 minutes were compared prior to Target: Stroke (2003-2009), during Phase I (2010-2013), and during Phase II (Q2 2014-present) by weighted linear regression. Results: There were 131,166 intravenous tPA treated patients from 1397 GWTG-Stroke hospitals. Patient characteristics were similar during the study periods. Median DTN time declined from Phase I to Phase II: 66 minutes (IQR 51-87) to 54 minutes (IQR 41-71) and % of patients with DTN times ≤60 minutes increased from 42.0% to 62.7%, (P Conclusions: There has been accelerating progress in achieving more rapid DTN times for tPA administration among GWTG-Stroke hospitals participating in Target: Stroke Phase II. Nevertheless, opportunities remain to further improve the timeliness of care and clinical outcomes.

Introduction: Patients who present to the hospital during off-hours receive sub-optimal care and experience worse outcomes, often attributed to reduced staffing. It is unknown whether stroke patients receive less guideline-adherent care and experience worse outcomes when medical providers attend scientific meetings. The AHA International Stroke Conference (ISC) is the premier US conference for cerebrovascular disease and is well attended by stroke clinicians. Methods: The national Get With The Guidelines - Stroke (GWTG-Stroke) dataset was analyzed from 2009-2015 to identify acute ischemic stroke (AIS) patients admitted during: 1) the week of ISC, and 2) the 2 weeks before and 2 weeks after ISC. We compared adherence to GWTG-Stroke quality measures and outcomes for AIS patients admitted during these two time periods using univariable and multivariable analysis, including both patient and hospital level variables. Results: Overall, 69,738 AIS patients were included, mean age 72, 52% female, and 29% non-white. There was no difference between the average weekly number of AIS cases admitted during ISC weeks versus non-ISC weeks (1,984 vs 1,997, p= 0.95). Patient and hospital characteristics were also similar between ISC vs. non-ISC time periods. No significant differences were noted in 14 quality of care metrics and 5 clinical outcomes between AIS patients treated during ISC vs. non-ISC weeks (Table). After adjusting for potential confounders, among patients who presented within 2 hours of onset there was no difference in the likelihood of receiving IV tPA within 3 hours (adjusted odds ratio 0.89, 95% confidence interval [CI] 0.77 - 1.03, p=0.13), nor in the likelihood of receiving IV tPA within 60 minutes of arrival (adjusted odds ratio 0.92, 95% CI 0.83 - 1.02, p=0.13). Conclusions: The treatment and outcome of patients who present with AIS to a GWTG-Stroke participating hospital are not degraded during the week of the International Stroke Conference.

Background: Seasonal variation in stroke occurrence and outcomes has been reported in small populational studies but the significance of a seasonal effect is uncertain. The important patient and climate variables underlying this phenomenon have not yet been identified. Methods: Using Get With The Guidelines-Stroke data from 2011 to 2015, we studied 457,638 consecutive ischemic stroke patients at 896 sites. We calculated the relative prevalence of acute stroke admissions in each season. Baseline characteristics and discharge outcomes were compared across seasons and the effects of season, climate region (as defined by the National Climatic Data Center), and climate variables on outcomes were analyzed using logistic regression. In secondary analyses, odds ratios were calculated for various outcomes. Results: Among all cases of ischemic stroke, there was significant difference in the frequency distributions of cases across seasons (p 3 (43.7%). P Conclusions: More patients presented with acute ischemic stroke in winter relative to other seasons, accompanied by trends toward poorer outcomes. Although an association with mortality was seen for winter in our unadjusted analysis, confounding variables likely exist. Precipitation and temperature were independently associated with stroke mortality.

Background and Purpose— Although the use of antiplatelet therapy (APT) is associated with the risk of intracerebral hemorrhage (ICH), there are limited data on prestroke APT and outcomes, particularly among patients on combination APT (CAPT). We hypothesized that the previous use of antiplatelet agents is associated with increased mortality in ICH. Methods— We analyzed data of 82 576 patients with ICH who were not on oral anticoagulant therapy from 1574 Get with the Guidelines-Stroke hospitals between October 2012 and March 2016. Patients were categorized as not on APT, on single-APT (SAPT), and CAPT before hospital presentation with ICH. We described baseline characteristics, comorbidities, hospital characteristics and outcomes, overall and stratified by APT use. Results— Before the diagnosis of ICH, 65.8% patients were not on APT, 29.5% patients were on SAPT, and 4.8% patients were on CAPT. There was an overall modest increased in-hospital mortality in the APT group versus no APT group (24% versus 23%; adjusted odds ratio, 1.05; 95% confidence interval, 1.01–1.10). Although patients on SAPT and CAPT were older and had higher risk profiles in terms of comorbidities, there was no significant difference in the in-hospital mortality among patients on SAPT versus those not on any APT (23% versus 23%; adjusted odds ratio, 1.01; 95% confidence interval, 0.97–1.05). However, in-hospital mortality was higher among those on CAPT versus those not on APT (30% versus 23%; adjusted odds ratio, 1.50; 95% confidence interval, 1.39–1.63). Conclusions— Our study suggests that among patients with ICH, previous use of CAPT, but not SAPT, was associated with higher risk for in-hospital mortality.

Background and Purpose— Stroke survivors identify home-time as a high-priority outcome; there are limited data on factors influencing home-time and home-time variability among discharging hospitals. Methods— We ascertained home-time (ie, time alive out of a hospital, inpatient rehabilitation facility, or skilled nursing facility) at 90 days and 1-year post discharge by linking data from Get With The Guidelines-Stroke Registry patients (≥65 years) to Medicare claims. Using generalized linear mixed models, we estimated adjusted mean home-time for each hospital. Using linear regression, we examined associations between hospital characteristics and risk-adjusted home-time. Results— We linked 156 887 patients with ischemic stroke at 989 hospitals to Medicare claims (2007–2011). Hospital mean home-time varied with an overall unadjusted median of 59.5 days over the first 90 days and 270.2 days over the first year. Hospital factors associated with more home-time over 90 days included higher annual stroke admission volume (number of ischemic stroke admissions per year); South, West, or Midwest geographic regions (versus Northeast); and rural location; 1-year patterns were similar. Lowest home-time quartile patients (versus highest) were more likely to be older, black, women, and have more comorbidities and severe strokes. Home-time variation decreased after risk adjustment (interquartile range, 57.4–61.4 days over 90 days; 266.3–274.2 days over 1 year). In adjusted analyses, increasing annual stroke volume and rural location were associated with significantly more home-time. Conclusions— In older ischemic stroke survivors, home-time post discharge varies by hospital annual stroke volume, severity of case-mix, and region. In adjusted analyses, annual ischemic stroke admission volume and rural location were associated with more home-time post stroke.

Background and Purpose— Predictive scores are important tools for stratifying patients based on the risk of future (cerebro)vascular events and for selecting potential prevention therapy. Recently, the Essen Stroke Risk Score (ESRS) was derived from cerebrovascular patients in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial. We aimed to validate the ESRS in a large cohort of outpatients with previous transient ischemic attack or stroke from the REduction of Atherothrombosis for Continued Health (REACH) Registry. Methods— We included 15605 outpatients with a qualifying stroke or transient ischemic attack and with clinical follow-up at 1 year. Patients with atrial fibrillation were excluded. We stratified 1-year cumulative rates for fatal and nonfatal stroke as well as combined major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) by the individually calculated stroke risk profile according to the ESRS and compared it with the 1-year event rates in the CAPRIE data subset of 6431 cerebrovascular patients. Results— The 1-year rate for recurrent stroke (or combined cardiovascular events) in the stable outpatient population of REACH increased steadily and significantly from 1.82 (2.41) in patients with ESRS 0 to 6.84 (11.48) for ESRS >6. The overall as well as stratified risk of recurrent stroke and cardiovascular events was lower than for cerebrovascular patients in CAPRIE. Conclusions— In outpatients with previous stroke or transient ischemic attack, the ESRS accurately stratifies the risk of recurrent stroke or major vascular events. Patients with a high ESRS should be candidates for intensified secondary prevention strategies.

Background: The necessity for rapid evaluation and treatment with intravenous tissue plasminogen activator (tPA) in acute ischemic stroke may increase the risk of administrating tPA to patients without a stroke (“stroke mimics”). Methods: Using data from the Get With The Guidelines Stroke Registry from 2009 to 2015, we identified 90,746 patients treated with tPA within 4.5 hours of symptom onset. We documented use of tPA in stroke mimics, defined as patients initially thought to have a stroke but without a final diagnosis of one, and compared patient characteristics and outcomes between tPA-treated mimics vs. ischemic strokes. Results: Overall, only 0.8% (728) of all tPA cases were given to stroke mimics, ranging from 0.2% in 2009 Q1 to 1.3% in 2015 Q1. The most common documented diagnoses in tPA-treated mimics were migraine (15.6%), functional disorder (9.4%), and seizure (7.2%). Compared with tPA-treated true stroke patients, tPA-treated mimics were younger (median 52 vs. 72 years), had lower prevalence of atrial fibrillation, coronary artery disease, dyslipidemia, hypertension, heart failure, had less severe National Institute of Health Stroke Scale (median 7 vs. 10), but higher prevalence of prior stroke/transient ischemic attack (34.4% vs. 25.5%), all p Conclusions: In this large nationwide cohort of patients treated with tPA, only 1 in 125 patients who received tPA for presumed stroke was a false positive and complication rates associated with tPA administration to stroke mimics were quite low. Nonetheless, there still may be opportunities to continue to improve the rapid and accurate diagnosis and treatment of ischemic stroke.

Background: Stroke is a key contributor to the global burden of disease and the second leading cause of death worldwide. Efforts to measure and improve care are rapidly extending to low and middle income countries. Yet there is lack of comparative assessment of characteristics and adherence to evidence-based performance measures in acute ischemic stroke for most world regions. Methods: We analyzed data of consecutive acute ischemic stroke patients in the Get With The Guidelines Stroke (n=194,876 from 1548 sites) and the China National Stroke Registry (n=19,604 from 217 sites) between 2012 and 2013. Patient characteristics and adherence to guideline-based performance measure in both countries were compared. Results: Compared with their US counterparts, Chinese patients were much younger (mean 64.8 vs. 70.5 years), had lower prevalence of comorbidities except for prior stroke/TIA and smoking, had less severe stroke (NIHSS, mean 5.4 vs. 6.8) and more delay from symptom onset to arrival (median 22 vs. 11 hours) (all p80%), although numerically lower than in the US. The largest differences between performance measure adherence in Chinese and US care were seen in timeliness of tPA treatment, venous thromboembolism prophylaxis, lipid lowering therapy, anticoagulation for atrial fibrillation, and rehabilitation assessment (Figure). Conclusion: We found important differences in clinical characteristics and gaps in adherence to certain performance measures between China and the US. National efforts are needed for continued improvements in acute ischemic stroke care in both countries.

Background: The benefits of intravenous tPA in acute ischemic stroke are time-dependent with guidelines recommending a door-to-needle (DTN) time of ≤60 minutes. The implementation of Target: Stroke Phase I in 2010 was associated with an increase in the proportion of patients with DTN times ≤60 minutes in the US from 28.9% in 2009 to 51.0% in 2013. This study aims to assess whether these improvements in DTN times could be maintained or further improved since the launch of Target: Stroke Phase II in Q2 2014. Methods: Target: Stroke Phase II identified and disseminated additional best practice strategies, provided updated clinical decision support tools, and set new hospital recognition goals. Rates of DTN times ≤60 minutes were compared during final 4 quarters of Phase I (Q4 2012-Q3 2013) vs. Phase II (Q2 2014-Q1 2015) and overall by linear weighted regression. Results: There were 99,176 intravenous tPA treated patients from 1228 GWTG-Stroke hospitals. Patient characteristics were similar during Phase I and II. Median DTN time significantly declined from the last 4 quarters of Phase I to the first 4 quarters of Phase II: 61 minutes (IQR 47-81) to 57 minutes (IQR 43-74) (P Conclusions: The timeliness of tPA administration is continuing to improve in GWTG-Stroke hospitals participating in Target: Stroke Phase II. Nevertheless, ongoing quality improvement efforts will be required to meet the goals of ≥75% of patients with DTN times ≤60 minutes and ≥50% of patients with DTN times ≤ 45 minutes.

Background: Prior studies have demonstrated that women and black patients with acute ischemic stroke were significantly less likely to be treated with intravenous tPA with door-to-needle (DTN) times of ≤60 minutes. Whether stroke quality improvement programs can impact care to a similar degree among sex and race/ethnic groups has not been well studied. This study aims to assess sex and race/ethnicity specific improvements in DTN times before and after the launch of Target: Stroke Phase I in 2010. Methods: Target: Stroke identified and disseminated 10 best practice strategies, provided clinical decision support tools, and set hospital recognition goals. Rates of DTN times ≤60 minutes and cumulative improvements pre- 2003-2009 were compared to post-Target Stroke 2010-2013 for sex and race/ethnic groups. Data were adjusted for patient and hospital characteristics. Results: There were 71,169 intravenous tPA treated patients (27,303 pre-; 43,866 post-Target Stroke) from 1030 GWTG-Stroke hospitals. Patients were median age 72, 50.1% women, and 72.0% white, 13.8% black, and 6.6% Hispanic. Overall, patients with DTN times ≤ 60 minutes increased from 26.5% (95% CI 26.0-27.1%) pre-intervention to 41.3% (95% CI 40.8-41.7%) post-intervention (P Conclusions: The implementation of Target: Stroke was associated with equitable improvements in DTN times for men and women and for black, white, and Hispanic ischemic stroke patients. These findings highlight the role that quality improvement programs can play in providing more timely and effective stroke care for all patients, irrespective of sex and race/ethnicity.

Background and Purpose— Intravenous tissue-type plasminogen activator (tPA) is a proven treatment for acute ischemic stroke, but there has been limited evaluation among patients aged ≥90 years. Methods— We analyzed data from the Get With The Guidelines–Stroke national quality improvement registry from January 2009 to April 2013. Frequency, determinants, and outcomes of tPA use were compared among patients aged ≥90 and 3 younger age groups (18–64, 65–79, and 80–89 years). Results— Among 35 708 patients from 1178 sites who arrived within 2 hours of time last known well and received tPA, 2585 (7.2%) were ≥90 years. Compared with younger patients, the rate of tPA use among patients without a documented contraindication was lower among patients aged ≥90 years (67.4% versus 84.1% in 18–89-year olds; P Conclusions— The use of intravenous tPA among those aged ≥90 years is lower than in younger patients. When fibrinolytic therapy is used, the risk of symptomatic hemorrhage is not higher than in 66- to 89-year olds; however, mortality is higher and functional outcomes are lower.

Purpose— Our goal is to provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke. The intended audience is physicians and other emergency healthcare providers who treat patients within the first 48 hours after stroke. In addition, information for healthcare policy makers is included. Methods— Members of the panel were appointed by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee and represented different areas of expertise. The panel reviewed the relevant literature with an emphasis on reports published since 2003 and used the American Heart Association Stroke Council’s Levels of Evidence grading algorithm to rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and approval by the American Heart Association Science Advisory and Coordinating Committee. It is intended that this guideline be fully updated in 3 years. Results— Management of patients with acute ischemic stroke remains multifaceted and includes several aspects of care that have not been tested in clinical trials. This statement includes recommendations for management from the first contact by emergency medical services personnel through initial admission to the hospital. Intravenous administration of recombinant tissue plasminogen activator remains the most beneficial proven intervention for emergency treatment of stroke. Several interventions, including intra-arterial administration of thrombolytic agents and mechanical interventions, show promise. Because many of the recommendations are based on limited data, additional research on treatment of acute ischemic stroke is needed.

Background and Purpose— Mild stroke (MS) and rapidly improving stroke (RIS) symptoms are common stroke presentations. Our objective is to describe the short-term outcomes in this population. Methods— A retrospective analysis of patients with ischemic stroke in the Get With The Guidelines–Stroke registry who arrived ≤4.5 hours from symptom onset not treated with thrombolytics because of MS and RIS. Outcomes included in-hospital death, home discharge, independent ambulation at discharge, and length of stay; these were analyzed for the categories of MS, RIS, and MS+RIS. Multivariable models evaluated the associations of individual and hospital covariates with outcomes. Results— Among 42 394 patients with MS and RIS not treated with thrombolytics, 27% were not discharged directly home, 27.2% did not ambulate independently, and 61.1% had length of stay ≥3 days, despite a low in-hospital mortality of 0.8%. Adjusted outcomes were better for MS+RIS compared with MS; RIS also had better independent ambulation and home discharge compared with MS. Among those with a documented National Institutes of Health Stroke Scale, 25% of those with National Institutes of Health Stroke Scale 0 to 5 and half of those with National Institutes of Health Stroke Scale >5 could not be discharged directly to home or ambulate independently. Older individuals, women, blacks, transport by ambulance, delayed arrival, greater severity and greater burden of vascular risk factors, except for dyslipidemia, had worse adjusted outcomes for home discharge and independent ambulation. Conclusions— A significant proportion of patients with MS and RIS not treated with thrombolytics have suboptimal discharge outcomes. We found significant differences between MS, RIS, and MS+RIS and identified factors associated with worse outcomes.

Background and Purpose— Whether a history of carotid endarterectomy influences patient compliance with medical treatments and physician attitude toward treatments after ischemic stroke or transient ischemic attack (TIA) is not well known. Methods— We studied the baseline data of 18 467 ischemic stroke and TIA patients from the international REduction of Atherothrombosis for Continued Health (REACH) Registry and investigated the impact of a history of endarterectomy on the secondary medical prevention measured by the use of antiplatelet agents and statins, and by the control of cholesterol level, glucose level, and blood pressure. Results— Among the patients with a history of ischemic stroke or TIA, those with a history of endarterectomy (n=1474) were more likely to receive antiplatelet agents and statins, to have a blood pressure P P P Conclusions— Carotid endarterectomy is associated with a higher use of antiplatelet agents and statins in stroke/TIA patients. The absence of such an association with blood pressure and blood glucose control suggests that the individual determinants of the quality of the secondary medical prevention vary from one risk factor to another and from one class of drugs to another.