rt-PA For Acute Ischemic Stroke Research Articles

Hemorrhagic transformation after thrombolytic therapy for acute ischemic stroke: Accuracy and improvement of existing predictive models in a rural population of the Midwest.

Hemorrhagic transformation (HT) after rtPA in acute ischemic stroke is a known complication of thrombolytic therapy. Several grading scales have been introduced in clinical practice, aiming to quantify the risk of HT before rtPA is administered. The goals of this study are to evaluate the performance of existing grading scales in a rural population of the Midwest and improve the existing models. This is a retrospective study of stroke patients treated with thrombolytics at Southern Illinois Healthcare from July 2017 to August 2024. Demographics, clinical presentations, laboratory values, neuroimaging, and stroke metrics were collected. HT found on neuroimaging within 24h after rtPA was reviewed. mRS at 30days was noted. The cohort was divided in two groups: HT and no-HT. The two groups were compared by univariate analyses. SEDAN, HAT, MSS, and THRIVE scores were calculated, and multivariable logistic regression analysis was run for each model. Area under the receiver operating characteristic curve (AUC) with its 95% confidence interval was calculated for each grading scale. P value was set at 0.05. Out of 279 patients included in this study, HT occurred in 8.6% of patients (n=24), whereas 91.4% (n=255) had no-HT. The two groups were similar in baseline characteristics and stroke severity. HT group had significantly worse mRS 0-2 at 30days (42% vs. 69%, p<0.05). SEDAN score demonstrated the highest accuracy in predicting HT after rtPA (AUC=0.65, 95% CI:0.56-0.75). Adding 1 point for smoking to the score, SEDAN-S, improved the accuracy of the model (AUC=0.67, 95% CI:0.57-0.77). Existing predictive scales of HT after rtPA underperform in our rural population. Among those, SEDAN score is the most accurate predictor. Adding smoking status to the score improves its accuracy. Further larger studies in similar rural populations should be performed to confirm our results.

Treatment Delays for Patients With Acute Ischemic Stroke in a Rural Arkansas Emergency Department: A Retrospective Chart Review.

Objective The goal of this study is to evaluate treatment times regarding acute ischemic stroke and identify barriers to implementing stroke care at the Ouachita County Medical Center Emergency Department. Methods A retrospective review of medical records was conducted of patients who presented with acute ischemic stroke to the Ouachita County Medical Center Emergency Department between 2020 and 2023 and received intravenous (IV) r-tPA. The primary focus of this study was to analyze door-to-needle time withIV r-tPA. To determine areas of improvement, this studyexamined door-to-initial physician evaluation, door-to-CT, door-to-tele neurologist evaluation, and door-to-IV r-tPA administration. Results A total of 26 patients who received treatment with IV r-tPA for acute ischemic stroke were included in this study. Twenty-three patients (88%; n=26)received IV- r-tPA within the recommended 60-minute window with a mean treatment time of 44.5 minutes. The mean door-to-physician evaluation time for patients presenting with acute ischemic stroke was 1.81 minutes. All patients received CT scans within 28 minutes of arrival with the mean time being 5.08 minutes. Teleneurologist evaluation was initiated within 59 minutes of presentation with a mean time of 25.19 minutes. Conclusion Evaluation of treatment times at the Ouachita County Medical Center Emergency Department confirms that stroke care received at this facility adheres to the recommendations outlined by the American Stroke Association. Nevertheless, clinicians should always strive for improvement. Through extensive evaluation of the treatment process, we were able to provide recommendations to further decrease treatment times and improve overall clinical outcomes.

Analysis of Safety and Efficacy of the Early Initiation of Antithrombotic Secondary Prevention in Patients Treated with Intravenous Thrombolysis for Acute Ischemic Stroke.

Background and Objectives: Current guidelines and the alteplase product insert recommend that antithrombotic therapy be avoided within 24 h of intravenous thrombolytic therapy with rt-PA in acute ischemic stroke. Therefore, the rate of stroke recurrence is unclear in terms of early neurological deterioration, which we could prevent with the early administration of antithrombotic therapy. We do not know the effect of early antithrombotic therapy after intravenous thrombolysis with rt-PA in acute stroke on the outcome in patients after 90 days either. Design: Prospective monocentric observational cohort study. Methods: Data were collected from consecutive patients treated with alteplase for acute ischemic stroke between January 2015 and January 2023. We examined functional outcome at 90 days, including the risk of symptomatic intracranial hemorrhage and mortality rate as safety indicators and stroke recurrence events in both early and standard antithrombotic therapy at 24 h after intravenous thrombolysis. Results: A total of 489 patients were included, of which 278 (56.9%) were men. Of these, 407 (83.2%) patients received early antithrombotic therapy. No symptomatic intracranial hemorrhage occurred in any participants. There was a significantly higher number of patients with an excellent outcome (mRS 0-1) in early antithrombotic treatment (211 (53.1%) versus 28 (34.6%) in standard antithrombotic treatment (p = 0.002, OR 0.47, 95% CI: 0.28-0.76). Conclusions: Early antithrombotic treatment after intravenous therapy in patients with acute ischemic stroke revealed no safety concerns compared with standard antithrombotic therapy and resulted in a significantly higher proportion of patients with an excellent functional outcome.

Argatroban as an Add-On to rtPA in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Current treatment options for acute ischemic stroke, including intravenous thrombolysis (IVT) and mechanical thrombectomy, have undoubtedly revolutionized stroke care. The need for additional treatment options has brought into the light direct thrombin inhibitors (DTIs) and, specifically, argatroban as a promising candidate. However, there is uncertainty regarding the safety of adding argatroban to IVT, mainly due to the increased hemorrhagic risk. In this study, we performed a systematic review and meta-analysis examining the safety and efficacy of argatroban as an add-on treatment for IVT. The following databases were searched from inception until the 14th of May 2023: Pubmed/MEDLINE, ClinicalTrials.gov, the EU Clinical Trials Register, EMBASE/Scopus, and the Cochrane Library. Only randomized clinical trials (RCTs) enrolling patients with acute ischemic stroke who underwent IVT evaluating the add-on use of any DTIs were selected for the systematic review and further meta-analysis. The PRISMA guidelines were followed at all stages. Four studies with argatroban were included in the final analysis. Analysis of risk ratio and relative risk shows that the add-on therapy with argatroban seems to be effective and favors a good clinical outcome (mRS 0-2) at 90 days, similar to that of alteplase. All studies showed a low pooled incidence of symptomatic intracerebral hemorrhage (5%), parenchymal hematoma (3%), and other major bleeding (1%). Argatroban as an add-on treatment to IVT seems not to be associated with excessive bleeding risk; however, its efficacy remains unproven. According to this synopsis of the currently available evidence, it is premature to use argatroban as an add-on to IVT treatment outside the current clinical trial setting.

Low-dose intravenous recombinant tissue plasminogen activator in acute ischemic stroke without large vessel occlusion screened by 3T MRI.

Globally, there are more than six million deaths due to cerebrovascular disease, which is the second leading cause of death. Although the imaging findings of magnetic resonance imaging (MRI) are more accurate than computed tomography for acute ischemic stroke (AIS), it is uncommon in recombinant tissue plasminogen activator (rTPA) treatment. Alteplase is not only strongly recommended treatment for acute ischemic stroke within 4.5 hours, but also decreases the disability and mortality rate. Besides, low-dose rTPA was associated with significant reductions in symptomatic intracerebral hemorrhage (sICH), compared with standard one. However, the benefits of low-dose rTPA for the treatment of AIS without large vessel occlusion (LVO) have not been fully demonstrated. We evaluated whether the low-dose rTPA in AIS without LVO could improve prognosis in patients three months post-treatment. This was a cross-sectional study on patients with AIS treated within 4.5 hours of symptom onset admitted to Can Tho S.I.S General Hospital between February 2019 and July 2021. The eligibility criteria were patients aged > 18 years treated with low-dose rTPA (0.6 mg/kg) and screened by 3T MRI. Patients with a pre-hospital modified Rankin score (mRS) ≥ 2 points, intracranial hemorrhage, LVO, or ≥ 3 microbleeds on brain MRI were excluded. The primary outcomes were the favorable outcome rate at three months and safety, which were evaluated by the rates of intracranial hemorrhage and mortality at three months. This study enrolled 92 eligible patients between February 2019 and July 2021. Their National Institute of Health Stroke Scale (NIHSS) scores were 7.5 ± 3.7 at admission, 3.3 ± 3.5 at discharge or seven days after discharge, and 2.2 ± 2.8 at three months. Their mRS were 2.9 ± 0.8 at admission, 1.4 ± 1.3 at discharge or seven days after discharge, and 1.1 ± 1.1 at three months. Elevated cardiac enzymes, age ≥ 75 years, and body mass index ≥ 25 were associated with increased poor outcomes at three months. While AIS was more common in men than women, a similar number of men (33.3%) and women had poor mRS. Three patients had complications associated with low-dose rTPA treatment: one (1.1%) had intracranial hemorrhage, one (1.1%) had new infarcts, and one (1.1%) had gastrointestinal bleeding. No deaths occurred within three months. Our study indicates the efficacy and safety of low-dose rTPA treatment for AIS without LVO within 4.5 hours. Patient selection for rTPA by 3T MRI decreased complications and mortality.

New Remote Cerebral Microbleeds on T2*-Weighted Echo Planar MRI After Intravenous Thrombolysis for Acute Ischemic Stroke.

BackgroundThe main and well-defined complication of intravenous administration of recombinant tissue plasminogen activator (tPA) in patients with acute ischemic stroke (AIS) is symptomatic intracranial hemorrhage (sICH). However, rtPA might also be connected with the formation of cerebral microbleeds (CMBs), located remotely from the ischemic lesions, that may remain clinically silent. This association might be important because the load of CMBs has been associated with cognitive impairment. We investigated whether administration of rtPA in AIS results in the appearance of new CMBs and if the initial load of CMBs is associated with hemorrhagic transformation.MethodsA total of fifty-nine consecutive patients with AIS treated with rtPA underwent MRI including T2*-weighted Echo Planar Imaging (T2*-EPI) shortly before and 7–9 days after rtPA administration. We calculated the load of new CMBs located outside the MR diffusion restriction area in the follow-up imaging and assessed hemorrhagic transformation with ECASS-II scoring.ResultsA total of forty-nine patients were included for the final analysis. On initial T2*-EPI-GRE, 37 baseline microbleeds (CMBs) were observed in 14 patients (28.6%). On follow-up T2*-EPI-GRE amount of CMBs increased to a total number of 103. New CMBs were found in 5 (14.3%) of 35 patients without and in 9 (64.3%) of 14 with any baseline CMBs. Multiple logistic regression analysis indicated that presence of baseline CMBs (risk ratio [RR] 5.95, 95% CI 2.69–13.20, p < 0.001) and lower platelets level (risk ratio [RR] 0.992, 95% CI 0.986–0.998, p = 0.007) were independently associated with new CMBs. The baseline load of CMBs was not associated with the risk of hemorrhagic transformation.ConclusionIn this study, new CMBs were found in nearly 30% of patients with AIS on the 7–9 days after rtPA treatment. Baseline CMBs correlated with a higher risk of new CMBs appearing after the rtPA treatment, independently of other factors. At the same time, in our sample, baseline CMBs did not correlate with an increased risk of hemorrhagic transformation. Since the associations between the CMBs load and cognitive impairment have already been proved, further studies are warranted to investigate possible associations between the thrombolytic treatment of patients with AIS, mainly those with baseline CMBs, and the risk of earlier cognitive decline.

Abstract P17: Outcomes After Thrombolysis for Ischemic Stroke in Costa Rica Compare Favorably With International Cohorts

Background: More than 70% of strokes occur in resource-poor countries. Outcomes are often not well documented. rt-PA for acute ischemic stroke was approved in 2012 for use in Costa Rica (CR). A hub and spoke model was initiated and a dataset established, the CR Stroke Registry Program (CRSRP) for conditional- and post-approval monitoring. Here, we compared CRSRP rt-PA outcomes to similarly treated subjects from the 1995 NINDS rt-PA trial and the 2019 CLOTBUST-ER control arm. Methods: Subjects were matched using a published pairing methodology and day 7-10/discharge modified Rankin Score (mRS), symptomatic intracerebral hemorrhages (SICH) and early mortality compared. A mortality model was generated from 15 randomized controlled trials (RCTs) and outcomes compared at similar baselines. SICH rates were compared with other cohorts: Get With The Guidelines (GWTG), a combined international IV thrombolysis trial pool, and 2 Ibero-American populations. Results: Of 424 CRSRP patients, 284 receiving rt-PA under 3 hrs were matched with 308 NINDS subjects. 131 non-diabetic CRSRP subjects, treated within 4.5 hrs, NIHSS 10 - 24 and Alberta Stroke Program Early CT Score (ASPECTS)&gt;7, were matched with 300 CLOTBUST-ER subjects. Percent achieving either mRS 0-1 or 0-2 did not differ between CRSRP and either NINDS or CLOTBUST-ER (mRS 0-1: CRSRP:33.9% vs NINDS:33.6%; CRSRP:23.8% vs CLOTBUST-ER:27.0%, all p&gt;=.05 / mRS 0-2: CRSRP:40.0% vs NINDS:41.4%; CRSRP:31.1% vs CLOTBUST-ER:36.1%, all p=&gt;.05). Mortality was higher for CRSRP vs CLOTBUST-ER (6.6% vs 0.8%; p=0.05) but not vs NINDS (6.8% vs 4.3%; p=0.3). A predictive model (R 2 =0.39) showed neither cohort exceeded expected pooled mortality, with CLOTBUST-ER the lowest mortality. SICH rate was higher in CRSRP vs CLOTBUST-ER (7.3% vs 0.0% p=0.008) but not vs NINDS (5.7% vs 6.8% p=0.7)). SICH rates were not higher when compared with 4 international cohorts. Conclusion: Functional outcomes of Costa Rican patients receiving rt-PA compared favorably with 2 RCTs (NINDS and CLOTBUST-ER). SICH and mortality were higher than CLOTBUST-ER, although both were within expected range compared to other international cohorts. Systems of care development in order to further lower SICH and participate in the endovascular era are underway.

Combined therapy of intensive statin plus intravenous rt-PA in acute ischemic stroke: the INSPIRE randomized clinical trial.

To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20mg daily × 14days) and the control group (rosuvastatin 5mg daily × 14days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90days. The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran-Mantel-Haenszel test). The incidence of primary safety endpoint events (sICH) in 90days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. URL: http://www.chictr.org . Unique identifier: ChiCTR-IPR-16008642.

Characteristics and Outcomes of Patients who Refuse Intravenous Thrombolysis for Acute Ischemic Stroke - The San Diego Experience

PurposeIntravenous Thrombolysis (IV rt-PA) is administered in <10% of ischemic stroke patients. In rare cases, patients or caregivers refuse IV rt-PA treatment even when recommended by stroke practitioners. We sought to assess the characteristics and outcomes of patients who refuse IV rt-PA for acute ischemic stroke, and to compare outcomes between those who were treated with IV rt-PA and those who refused. MethodsWe examined data from the prospectively collected, IRB approved UC San Diego Stroke Registry who presented as a “stroke code” from July 2004 to July 2019 at two academic facilities and five community hospitals. Patients were included if they presented within 4.5 hours of symptom onset or last seen normal, had a “stroke code” alert activated, and were either treated with IV rt-PA or the reason for exclusion was patient/family refusal. Patients were considered “refusers” if IV rt-PA was recommended by the provider during the stroke code and the patient and/or legally authorized representative declined treatment. Baseline demographics, baseline National Institutes of Health Stroke Scale (NIHSS), treatment times and 90-day Modified Rankin Scale (mRS) were collected. Patients who refused IV rt-PA were compared to those that were treated with IV rt-PA. Data was examined for frequencies and distribution. Chi squared was used to evaluate nominal variables. Continuous variables were assessed by Pearson correlation and t test. Kruskal-Wallis or ANOVA were used to evaluate group differences. ResultsA total of 1056 patients were included in the analysis. Forty-seven patients (4.5%) refused IV rt-PA. There were no significant socio-demographic differences between patients who were treated with IV rt-PA and those who refused. Compared to patients who were treated with IV rt-PA, patients who refused IV rt-PA had a significantly lower baseline NIHSS (4 vs 9, p < 0.0001) and higher baseline mRS (IQR 0-1.0 vs 0-2.8, p < 0.001). The time from arrival to treatment decision was significantly longer in patients who refused IV rt-PA (group mean 57.9 min vs 48.8 min, p = 0.03). Data for 90-day outcome was available for 556 (55.1%) patients treated with IV rt-PA and 20 (42.5%) patients who refused IV rt-PA. There was no difference in 90-day mRS between groups (p = 0.68). ConclusionsThere is a low rate of IV rt-PA refusal in our registry population which is similar to what previous studies have shown. We found that patients who refuse IV rt-PA have significantly milder deficits and significantly worse pre-morbid disability. We speculate that the longer “arrival to decision” time in the refuse IV rt-PA group is due to longer informed consent discussions. This analysis furthers the body of literature regarding rt-PA refusals.

Knowledge of the Egyptian emergency physicians about the use of rt-PA in acute ischemic stroke

BackgroundThe administration of recombinant tissue plasminogen activator (rt-PA) has increased the focus on acute ischemic stroke (AIS) as an emergency condition. The emergency physicians have to rapidly recognize the patients who are candidates for rt-PA and refer them to the specialized stroke team within the proper time window. The knowledge of the emergency physicians about the benefit and the drawbacks of this therapy is crucial and it affects their attitudes towards its use.ObjectiveTo apply a survey on the Egyptian emergency physicians aiming to investigate their knowledge about the use rt-PA therapy in AIS.MethodologyA self-administered questionnaire was sent to the emergency physicians who are working in three Egyptian governorates.ResultsOut of 120 emergency physicians, the total knowledge of the study group was good with a score of 7 ± 1.8/11. Most of the participants mentioned the correct answers (over 50%) for all items except for one question regarding the blood glucose control before the use of rt-PA. Significant positive correlation was noted between the knowledge score and the age.ConclusionsThe surveyed emergency physicians had a good knowledge about the use of rt-PA in AIS, yet, this knowledge is mainly theoretical. Therefore, tutorials, clinical training, and active engagement in the stroke care team are warranted to improve their clinical practice.

Thrombolytic Therapy with rt-PA for Acute Ischemic Stroke in Thailand: A Detailed Comparison of Community Hospitals with Regional Hospitals and Tertiary Care Hospitals. (4333)

Thrombolytic Therapy with rt-PA for Acute Ischemic Stroke in Thailand: A Detailed Comparison of Community Hospitals with Regional Hospitals and Tertiary Care Hospitals. (4333)

Randomized trial of argatroban plus recombinant tissue-type plasminogen activator for acute ischemic stroke (ARAIS): Rationale and design

Previous studies have implied the efficacy and safety of argatroban plus recombinant tissue-type plasminogen activator (r-tPA) in patients with acute ischemic stroke. Further trials are needed to establish convincing conclusions in a large sample size. Argatroban plus r-tPA for Acute Ischemic Stroke (ARAIS) trial is a multicenter, prospective, randomized, open-label, and blind-end point trial. The trial proposes to randomize 808 patients with acute ischemic stroke National Institutes of Health Stroke Scale (NIHSS score≥ 6 at the time of randomization) within 4.5 hours of symptom onset to receive argatroban (100 μg/kg bolus followed by an infusion of 1.0 μg/kg per minute for 48 hours) plus r-tPA or r-tPA alone. The primary end point is the proportion of patients with an excellent outcome of no clinically significant residual stroke deficits (modified Rankin scale 0-1) at 90 days. Secondary end points include the proportion of patients with a good outcome (modified Rankin scale 0-2) at 90 days, early neurological improvement (NIHSS score ≥2-point decrease) at 48 hours, early neurological deterioration (NIHSS score ≥4-point increase) at 48 hours, decrease in the NIHSS score from baseline to 14 days, and stroke recurrence or other vascular events at 90 days. Safety end points include symptomatic intracerebral hemorrhage, parenchymal hematoma type 2, and major systemic bleeding. ARAIS trial will evaluate whether argatroban plus r-tPA is superior to r-tPA alone in improving functional outcomes in acute ischemic stroke patients in a large sample population.

Differences between predictive factors for early neurological deterioration due to hemorrhagic and ischemic insults following intravenous recombinant tissue plasminogen activator

Early neurological deterioration (END) following intravenous recombinant tissue plasminogen activator (rt-PA) treatment is a serious clinical event that can be caused by hemorrhagic or ischemic insult. We investigated the differences in predictive factors for END due to hemorrhagic and END due to ischemic insults. Consecutive patients from four hospitals who received 0.6 mg/kg intravenous rt-PA for acute ischemic stroke were retrospectively recruited. END was defined as a National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points within 24 h compared with baseline. END was classified into those due to hemorrhagic (ENDh) or ischemic (ENDi) insult based on computed tomography (CT) or magnetic resonance imaging. Risk factors associated with ENDh and ENDi were investigated by comparison with non-END cases. A total of 744 patients (452 men, median 75 years old) were included. END was observed in 79 patients (10.6%), including 22 ENDh (3.0%) and 57 ENDi (7.7%), which occurred within a median of 7 h after treatment. Multivariate analyses showed that higher pretreatment NIHSS score (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.00–1.13) and pretreatment with antiplatelets (OR 2.84, 95% CI 1.08–7.72) were associated with ENDh. Extensive early ischemic change (Alberta Stroke Program Early CT Score ≤ 7 on CT or ≤ 6 on diffusion-weighted imaging; OR 2.80, 95% CI 1.36–5.64) and large artery occlusions (OR 3.09, 95% CI 1.53–6.57) were associated with ENDi. Distinct factors were predictive for the END subtypes. These findings could help develop preventative measures for END in patients with the identified risk factors.

Modified diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score including deep white matter lesions predicts symptomatic intracerebral hemorrhage following intravenous thrombolysis

The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used for the assessment of early ischemic changes (EICs) before thrombolysis. However, for symptomatic intracerebral hemorrhage (sICH) following intravenous recombinant tissue plasminogen activator (rt-PA), the prediction abilities of CT-ASPECTS, diffusion-weighted imaging (DWI)-ASPECTS, and DWI-ASPECTS including EICs in deep white matter (DWI-ASPECTS + W) are unclear. We investigated associations between each score and sICH following intravenous rt-PA. Data from consecutive patients who received intravenous rt-PA for acute ischemic stroke from 2005 to 2015 in four hospitals were retrospectively screened. We included data from patients who had undergone both CT and magnetic resonance imaging before thrombolysis and without evidence of posterior circulation stroke. We analyzed the ability of CT-ASPECTS, DWI-ASPECTS, and DWI-ASPECTS + W to predict sICH, accompanied by an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥ 4 within the initial 36 h. Of 455 patients (273 men, median 75 years old), sICH occurred in 15 patients (3.3%). Receiver operating characteristics curve analysis showed that the optimal cut-offs of CT-ASPECTS, DWI-ASPECTS, and DWI-ASPECTS + W for predicting sICH were ≤ 9 (sensitivity 60.0%, specificity 59.8%, c-statistic 0.625), ≤ 6 (sensitivity 53.3%, specificity 80.9%, c-statistic 0.718), and ≤ 8 (sensitivity 86.7%, specificity 55.9%, c-statistic 0.756), respectively. A DWI-ASPECTS + W of ≤ 8 was independently associated with sICH (odds ratio 5.21, 95% confidence interval 1.30–35.31) after adjustment for pretreatment with antithrombotic agents, pretreatment NIHSS score, and large artery occlusions. DWI-ASPECTS + W predicted sICH in patients with acute anterior circulation stroke receiving intravenous rt-PA.

Intravenous Thrombolysis Administration 3-4.5 h After Acute Ischemic Stroke: A Retrospective, Multicenter Study.

Background and Objectives: Intravenous recombinant tissue plasminogen activator (rt-PA) has been approved for acute ischemic stroke (AIS) within 3 h after onset and the treatment was then extended to 4.5 h. However, the Food and Drug Administration did not approve the indication in the expanded time window. This retrospective, matched cohort study aims to investigate the effectiveness and safety of rt-PA in AIS at 3–4.5 h after onset.Materials and Methods: The treatment group included AIS patients receiving rt-PA at 3–4.5 h after onset, otherwise complying with the regulation, in the stroke registries in 16 hospitals between 2008 and 2017. The control group included age- and sex-matched patients not receiving intravenous thrombolysis from the same registries, excluding those with contraindications. The primary outcome was modified Rankin Scale (mRS) 0–1 at day 90. The safety outcomes were any intracerebral hemorrhage (ICH), early neurological deterioration and 3-month mortality.Results: Each group had 374 patients. There were 34.0% of patients with 3-month mRS 0-1 in the treatment group vs. 22.7% in the control group with an odds ratio of 1.75 (95% confidence intervals, 1.27 to 2.42, P = 0.001). There was no difference in symptomatic ICH, early neurological deterioration and 3-month mortality rates between two groups. The 3-month mRS and symptomatic ICH did not differ significantly in patients receiving standard dose or low dose of rt-PA.Conclusions: Our results support the prescription of rt-PA in AIS patients 3–4.5 h after onset as an effective and tolerable treatment in their functional recovery.

AHA/ASA target: Stroke phase 2 goals achieved in UAE: “Acute stroke clinical pathway” significantly reduced ‘door-to-needle’ time in acute ischemic stroke

Target: Stroke was launched by the American Heart Association/American Stroke Association (AHA/ASA). Phase 1: To achieve Door-to-needle (DTN) within 60 minutes in ≥50%. of acute ischemic Stroke patients treated with IV rtPA. Phase 2: In acute ischemic stroke patients treated with IV rtPA, the Primary goal to achieve DTN times within 60 minutes in ≥75%; Secondary Goal to achieve DTN times within 45 minutes in ≥50%. We implemented “Acute Stroke Clinical Pathway” in 2015 to improve DTN time and Stroke care. We prospectively analysed 48 month (Jan 2015 – Dec 2018) data from Stroke Registry in AAH. We included patients who arrived within window period and received intravenous rtpA for acute ischemic stroke. Number of patients who met inclusion criteria was 21 in 2015, 20 in 2016, 10 in 2017 and 22 in 2018. In 2015, 86% were treated within 60 minutes and 38% within 45 minutes. In 2016, 100% were treated within 60 minutes and 45% within 45 minutes. In 2017, 80% were treated within 60 minutes and 40% within 45 minutes. In 2018, 100% were treated within 60 minutes and 73% within 45 minutes. We significantly improved DTN times since the implementation of “Acute Stroke Clinical Pathway”. In acute ischemic stroke patients treated with IV rtPA, we have achieved the Primary goal of AHA/ASA Target: Phase 2 to achieve DTN times within 60 minutes in ≥75% and the Secondary Goal of achieving DTN times within 45 minutes in ≥50%.

Thrombolytic therapy in older acute ischemic stroke patients with gastrointestinal malignancy or recent bleeding.

There are limited data on the safety of intravenous recombinant tissue plasminogen activator (rtPA) for treating acute ischemic stroke in patients with gastrointestinal malignancy or recent gastrointestinal bleeding within 21 days of their index stroke. To evaluate clinical outcomes in patients treated with rtPA for acute ischemic stroke who had gastrointestinal malignancy or recent gastrointestinal bleeding. We identified patients who were treated with rtPA for acute ischemic stroke between 2/2009 and 12/2015 from the Get With The Guidelines-Stroke linked to Medicare claims data. Gastrointestinal malignancy and recent gastrointestinal bleeding were defined as any gastrointestinal malignancy hospitalisation within one year prior to acute ischemic stroke and gastrointestinal bleeding hospitalisation within 21 days prior to acute ischemic stroke, respectively. Outcomes of interest included in-hospital mortality and bleeding complications. Among 40,396 patients aged 65 years or older treated with rtPA for acute ischemic stroke from 1522 sites (mean age [SD] 81.0 [8.1] years; 41.9% women), 136 (0.3%) had gastrointestinal malignancy (n = 96) or recent gastrointestinal bleeding (n = 43). Patients with gastrointestinal malignancy or bleeding had more severe stroke than those without (median NIHSS [interquartile range]: 14.0 [8.0-19.0] vs. 11.0 [6.0-18.0]). The rates of in-hospital mortality and life-threatening systemic haemorrhage were not significantly different between those with and without gastrointestinal malignancy or bleeding (mortality: 10.3% vs. 9.0%, adjusted odds ratio [aOR] 1.01, 95%CI 0.58-1.75; bleeding: 2.3% vs. 1.2%, aOR 1.72, 95%CI 0.58-5.11). In this observational cohort, we did not find increased risk of in-hospital mortality and bleeding in rtPA-treated patients with gastrointestinal malignancy or recent gastrointestinal bleeding.

Temporal Trends in Clinical Characteristics and Door-to-Needle Time in Patients Receiving Intravenous Tissue Plasminogen Activator: A Retrospective Study of 4 Hospitals in Japan

Background: Intravenous recombinant tissue plasminogen activator (rt-PA) has become a common treatment for acute ischemic stroke and has highly time-dependent benefits. We aimed to clarify temporal trends regarding the frequency and characteristics of patients receiving rt-PA and explore factors associated with door-to-needle time (DNT) in Japanese emergency hospitals. Methods: Consecutive patients who received intravenous rt-PA for acute ischemic stroke from October 2005 to December 2015 were retrospectively registered from 4 hospitals. Temporal trends in the frequency and characteristics of patients receiving rt-PA and factors associated with DNT were investigated. Results: A total of 750 patients, including 688 (420 men, median 75 years old) with out-of-hospital stroke, were registered. The frequency of patients receiving intravenous rt-PA for acute ischemic stroke continuously increased from 1.8% in 2005 to 9.5% in 2015. The proportion of patients who were elderly or had prestroke disability increased over time, while pretreatment stroke severity declined. The DNT gradually decreased (median 105 minutes in 2005, 61 minutes in 2015). According to multivariate regression analysis with correction for multiple comparisons, activation of a code stroke system (standardized partial regression coefficient (β) −.50, P < .001, q < .001), onset-to-door time (β −.15, P < .001, q < .001), pretreatment with antithrombotic agents (β .12, P < .001, q = .001), and year of treatment (β .11, P = .007, q = .011) were associated with DNT. Conclusions: Intravenous rt-PA was widely adopted in Japanese emergency hospitals. Characteristics of patients receiving intravenous rt-PA have changed over the past decade. Several factors, including the year of treatment, were associated with DNT, which has shortened over time.

Effect on door‐to‐needle recombinant tissue plasminogen activator administration times for acute ischemic stroke with and without an emergency department pharmacist

Study ObjectiveA paucity of data exists on the impact emergency department (ED) pharmacists have on a stroke team's door‐to‐needle (DTN) administration time of recombinant tissue plasminogen activator (rTPA). The purpose of this study was to assess the odds of achieving a DTN administration time for rTPA of 60 minutes or less with an ED pharmacist present.MethodsThis was a retrospective, cohort study of patients who received rTPA for acute ischemic stroke (AIS) from May 2017 to May 2018. Patients were included if they were at least 18 years old and received tPA for AIS in the ED. The primary outcome for this study was the likelihood of patients receiving a DTN administration time of 60 minutes or less with or without an ED pharmacist present during a stroke alert at a primary stroke center.ResultsThe electronic medical record of 184 stroke alert patients was reviewed, and 65 patients were included in the final analysis. Baseline characteristics were similar in all aspects. The odds ratio was 3.3 (95% confidence interval [CI]: 1.1‐9.6; P = 0.04) to achieve a DTN administration time of 60 minutes or less when an ED pharmacist was present. The ED pharmacist present group had faster median (47 minutes vs 60 minutes; P = 0.001) and average (49 minutes vs 63 minutes; P = 0.003) DTN administration times compared with the ED pharmacist not present group.ConclusionAn ED pharmacists present during a stroke alert at our faculty resulted in reduced overall DTN rTPA administration times and increased the odds of a patient receiving rTPA less than 60 minutes from arrival for AIS. Further study is required to determine if this finding can be replicated in other EDs.

Abstract TMP14: Intravenous Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Patients With Recent Myocardial Infarction

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.