Safe Implementation Of Treatments In Stroke Research Articles

Intravenous Thrombolysis in Posterior versus Anterior Circulation Stroke: Clinical Outcome Differs Only in Patients with Large Vessel Occlusion.

The safety and efficacy of intravenous thrombolysis (IVT) are well established in anterior circulation stroke (ACS) but are much less clear for posterior circulation stroke (PCS). The aim of this study was to evaluate the occurrence of parenchymal hematoma (PH) and 3-month clinical outcomes after IVT in PCS and ACS. In an observational, cohort multicenter study, we analyzed data from ischemic stroke patients treated with IVT prospectively collected in the SITS (Safe Implementation of Treatments in Stroke) registry in the Czech Republic between 2004 and 2018. Out of 10,211 patients, 1166 (11.4%) had PCS, and 9045 (88.6%) ACS. PH was less frequent in PCS versus ACS patients: 3.6 vs. 5.9%, odds ratio (OR) = 0.594 in the whole set, 4.4 vs. 7.8%, OR = 0.543 in those with large vessel occlusion (LVO), and 2.2 vs. 4.7%, OR = 0.463 in those without LVO. At 3 months, PCS patients compared with ACS patients achieved more frequently excellent clinical outcomes (modified Rankin scale [mRS] 0-1: 55.5 vs. 47.6%, OR = 1.371 in the whole set and 49.2 vs. 37.6%, OR = 1.307 in those with LVO), good clinical outcomes (mRS 0-2: 69.9 vs. 62.8%, OR = 1.377 in the whole set and 64.5 vs. 50.5%, OR = 1.279 in those with LVO), and had lower mortality (12.4 vs. 16.6%, OR = 0.716 in the whole set and 18.4 vs. 25.5%, OR = 0.723 in those with LVO) (p < 0.05 in all cases). In PCS versus ACS patients, an extensive analysis showed a lower risk of PH both in patients with and without LVO, more frequent excellent and good clinical outcomes, and lower mortality 3 months after IVT in patients with LVO.

Outcome predictors in anterior and posterior ischemic strokes: a study based on the Iranian SITS registry

Ischemic stroke is the major form of stroke with two separate vascular territories. Many risk factors are related to stroke outcomes in both territories. The present descriptive research was carried out on the basis of data obtained from the Safe Implementation of Treatments in Stroke (SITS) registry on Iranian intravenous thrombolysis ischemic stroke cases. Vascular territory involved in each case and three-month excellent outcome, functional independence, mortality rate, and brain hemorrhage occurrence were determined. Univariable and multivariable logistics regression analyses were utilized in order to investigate association of ischemic stroke outcomes with the vascular territory involved and other related factors. Among 1566 patients 95.4% was anterior circulation stroke patients and 4.6% was posterior circulation stroke cases. There is no significant association between vascular territory with mortality (OR of PCS vs ACS: 0.74, 95% CI 0.37–1.46), excellent functional outcome (OR 0.72, 95% CI 0.44–1.19), functional outcome (OR 0.86, 95% CI 0.52–1.42) and local hemorrhage (OR 0.98, 95% CI 0.30–3.21). Among major risk factors, age, diabetes, NIHSS score and admission duration, increased significantly odds of three-month mortality, excellent outcome, and functional independence in the multivariate analysis. The highest of odds was in NIHSS score with a dose–response association. The vascular territory was not an outcome predictor in ischemic strokes. The most important predictor was baseline NIHSS.

Functional Outcome of Endovascular Treatment in Patients With Acute Ischemic Stroke With Large Vessel Occlusion: Mothership Versus Drip-and-Ship Model in a Portuguese Urban Region.

Introduction Endovascular treatment (EVT) with mechanical thrombectomy and acute carotid stenting has become an integral part of the treatment of acute ischemic stroke with large vessel occlusion. Despite being included in the most recent stroke guidelines, only comprehensive centers can offer EVT and thus patients frequently need to be transferred from primary hospitals. We aimed to assess which pre-hospital model of care - direct admission to a comprehensive stroke center (mothership) or transfer to a comprehensive stroke center after the first admission to the nearest hospital (drip-and-ship) - had the most benefit in stroke patients in a Portuguese urban region. Methods We selected patients admitted to a comprehensive stroke center who underwent EVTs between January 2018 and December 2020, in Lisbon, Portugal. We used data from the Safe Implementation of Treatments in Stroke (SITS) International registry on stroke severity, previous modified Rankin Scale (mRS), time from symptom onset to the first admission, time from symptom onset to the procedure, and mRS three months post stroke. We defined an unfavorable outcome as having an mRS >2 at three months post stroke. For patients with previous mRS >2, an unfavorable outcome was defined as any increase in mRS at three months post stroke. Results We analyzed the data of 1154 patients, of which 407 were admitted through a mothership approach and 747 through a drip-and-ship approach. Both groups were similar regarding sociodemographic characteristics, stroke risk factors, previous disability, and stroke severity. Median onset-to-door time was higher (126 vs 110 minutes, p-value=0.002) but onset-to-procedure time was lower (199 vs 339 minutes, p-value<0.001) in the mothership group. The mothership group had a higher proportion of patients with mRS <3 at three months post stroke than the drip-and-ship group (41.3% vs 34.9%, p-value=0.035). Mortality was similar in both groups. A multivariate logistic regression model confirmed a lower probability of unfavorable outcomes with the mothership approach (OR = 0.677, 95% CI0.514-0.892, p-value=0.006). Surprisingly, onset-to-procedure time did not have an impact on functional outcomes. Conclusion Our findings show that the mothership model results in better functional outcomes for patients with acute ischemic stroke with large vessel occlusion. Further studies are needed to better define patient selection for this strategy and the impact of a mothership model in comprehensive stroke centers.

Pre-treatment spectral CT combined with CT perfusion can predict hemorrhagic transformation after thrombolysis in patients with acute ischemic stroke

ObjectiveTo investigate the value of pre-treatment spectral CT angiography (CTA) in predicting hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) treatment in acute ischemic stroke (AIS) patients. Materials and MethodsAIS patients who underwent IVT with recombinant tissue plasminogen activator and pre-treatment head and neck spectral CTA and head CT perfusion (CTP) from January 2018 to June 2020 were reviewed retrospectively. Finally, 20 patients were included in the HT group and 22 age-matched patients were included in the non-HT group. Spectral and CTP parameters of the region of interest on pre-treatment CTA axial raw images and CTP images, including the infarct core (IC) and ischemic penumbral (IP) regions, were recorded. The differences in clinical variables, CTP, collateral scores and spectral parameters between the two groups were analyzed. Three multivariate logistic regression models were then developed, where model 1 included clinical and spectral parameters, model 2 included clinical and CTP parameters and a combined model included clinical, CTP, and spectral parameters. Receiver operating characteristic analysis was used to evaluate the performance of the multivariate model. ResultsPatients with HT had higher Safe Implementation of Treatments in Stroke (SITS) score (p = 0.023), the volume of perfusion lesions (p = 0.005), the volume of IP (p = 0.003), the mean transit time (MIT) in the IC area (p = 0.012), as well as the TTP in IP area (p = 0.015) compared with patients without HT. The HT group showed significantly lower CBF in the IC area (p = 0.019), iodine concentration (p = 0.017) and the effective atomic number (p = 0.024) in the IP area than non-HT group. And the slope of the spectral curve of the HT group in the IP region was larger than that of the non-HT group (p = 0.023). Gender, age, SITS score, the volume of entire perfusion lesion, CBF and MIT in the IC area, TTP in the IP area, as well as iodine concentration in the IP area were included in the final multivariate model for predicting HT. And CBF in the IC area (OR = 0.779, 95 % CI:0.609–0.996, p = 0.046) as well as the iodine concentration of IP area (OR = 0.343, 95 % CI: 0.131–0.901, p = 0.030) were proved to be independent predictors for HT. The combined model including clinical, spectral, and CTP parameters, showed improved accuracy compared to the other two models, while the Delong test did not suggest a statistically significant difference (both p values > 0.05). ConclusionsThe iodine concentration of IP area derived from pre-treatment spectral CTA was an independent predictor of HT after IVT treatment for AIS patients. Moreover, multivariate models combined with clinical, spectral, and CTP parameters may be able to predict HT.

Machine Learning-Based Model for Prediction of Hemorrhage Transformation in Acute Ischemic Stroke After Alteplase.

Hemorrhage transformation (HT) is the most dreaded complication of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). The prediction of HT after IVT is important in the treatment decision-making for AIS. We designed and compared different machine learning methods, capable of predicting HT in AIS after IVT. A total of 345 AIS patients who received intravenous alteplase between January 2016 and June 2021 were enrolled in this retrospective study. The demographic characteristics, clinical condition, biochemical data, and neuroimaging variables were included for analysis. HT was confirmed by head computed tomography (CT) or magnetic resonance imaging (MRI) within 48 h after IVT. Based on the neuroimaging results, all of the patients were divided into the non-HT group and the HT group. Then, the variables were applied in logistic regression (LR) and random forest (RF) algorithms to establish HT prediction models. To evaluate the accuracy of the machine learning models, the models were compared to several of the common scales used in clinics, including the multicenter stroke survey (MSS) score, safe implementation of treatments in stroke (SITS) score, and SEDAN score. The performance of these prediction models was evaluated using the receiver operating characteristic (ROC) curve (AUC). Forty-five patients had HT (13.0%) within 48 h after IVT. The ROC curve results showed that the AUCs of HT that were predicted by the RF model, LR model, MSS, SITS, and SEDAN scales after IVT were 0.795 (95% CI, 0.647–0.944), 0.703 (95% CI, 0.515–0.892), 0.657 (95% CI, 0.574–0.741), 0.660 (95% CI, 0.580–0.740) and 0.655 (95% CI, 0.571–0.739), respectively. The RF model performed better than the other models and scales. The top four most influential factors in the RF importance matrix plot were triglyceride, Lpa, the baseline NIHSS, and hemoglobin. The SHapley Additive exPlanation values made the RF prediction model clinically interpretable. In this study, an RF machine learning method was successfully established to predict HT in AIS patients after intravenous alteplase, which the sensitivity was 66.7%, and the specificity was 80.7%.

Low-dose versus standard-dose alteplase for intravenous thrombolysis in patients with acute ischemic stroke in Iran: Results from the safe implementation of treatments in stroke registry

Background: Rates of intracranial hemorrhage (ICH) after intravenous thrombolysis (IVT) differ depending on ethnicity, one reason that few Eastern countries have approved a lower dose of alteplase. Data in this regard are scarce in the Middle Eastern region. Methods: The present retrospective study was performed on data extracted from the Safe Implementation of Treatments in Stroke (SITS) registry. Computed tomography (CT) image analysis was based on the SITS-Monitoring Study (SITS-MOST) definition for symptomatic ICH (SICH). Functional outcome at 3 months was assessed using the modified Rankin Scale (mRS). Multivariate logistic regression including adjusted analysis was used for comparison between groups. Results: Of 6615 patients, 1055 were enrolled. A total of 86% (n = 906) received a standard dose and 14% (n = 149) received a low dose of alteplase. Favorable 3-month outcome was achieved in 481 (53%) patients in the standard group and 71 (48%) patients in the low-dose group [adjusted odds ratio (AOR) = 1.24, 95% confidence interval (CI): 0.87-1.75, P = 0.218]. SICH occurred in 14 (1.5%) patients in the standard group and 3 (2%) patients in the low-dose group [odds ratio (OR) = 2.77, 95% CI: 0.36-21.04, P = 0.120]. At 3 months, mortality occurred in 145 (16.0%) patients in the standard group and 29 (19.4%) patients in the low-dose group (OR = 1.22, 95% CI: 0.78-1.91, P = 0.346). Conclusion: Low-dose compared to standard-dose alteplase for patients with acute ischemic stroke (AIS) was not associated with fewer hemorrhagic events and there was no significant difference in the favorable 3-month outcome (mRS: 0-2) or mortality rate.

Safety and early outcomes after intravenous thrombolysis in acute ischemic stroke patients with prestroke disability.

There are limited data on intravenous thrombolysis treatment in ischemic stroke patients with prestroke disability. We aimed to evaluate safety and outcomes of intravenous thrombolysis treatment in stroke patients with prestroke disability. We analyzed 88,094 patients treated with intravenous thrombolysis, recorded in the Safe Implementation of Treatments in Stroke (SITS) International Thrombolysis Register between January 2003 and December 2017, with available NIHSS data at stroke-onset and after 24 h. Of them, 4566 patients (5.2%) had prestroke disability, defined as a modified Rankin Scale score of 3-5. Safety outcome measures included Symptomatic Intracerebral Hemorrhage, any type of parenchymal hematoma on 24 h imaging scans irrespective of clinical symptoms, and death within seven days. Early outcome measures were 24-h NIHSS improvement (≥4 from baseline to 24 h). Patients with prestroke disability were older, had more severe strokes, and more comorbidities than patients without prestroke disability. When comparing patients with prestroke disability with patients without prestroke disability, there was however no significant increase in adjusted odds for symptomatic intracerebral hemorrhage (adjusted odds ratio 0.83 (95% CI 0.60-1.15) (absolute difference in proportion 1.17% vs. 1.27%)) or for parenchymal hemorrhage (adjusted odds ratio 0.96 (0.83-1.11) (7.51% vs. 6.34%)). The prestroke disability group had a significantly lower-adjusted odds ratio for a 24-h NIHSS improvement (adjusted odds ratio 0.79 (0.73-0.85) (45.95% vs. 48.45%)) and a higher adjusted odds ratio for seven-day mortality (aOR 1.40 (1.21-1.61) (10.40% vs. 4.93%)). Intravenous thrombolysis in acute ischemic stroke patients with prestroke disability was not associated with an increased risk of symptomatic intracerebral hemorrhage or parenchymal hemorrhage. Prestroke disability was however associated with a higher risk of early mortality compared to patients without prestroke disability.

Sex-related differences among ischaemic stroke patients treated with intravenous thrombolysis in Poland.

We investigated sex differences i n i schaemic s troke p atients t reated w ith i ntravenous a lteplase. We suggest that it is necessary to improve care for women with atrial fibrillation. Our data suggests that closer evaluation of treatment for ischaemic stroke in men and women is needed, preferably in the form of a prospective study. This was a multicentre analysis of 1,830 ischaemic stroke patients treated with alteplase from 2004 to 2012. Data was prospectively collected in the Safe Implementation of Treatments in Stroke (SITS) registry. The main outcome measures were symptomatic intracerebral haemorrhage (sICH) within 36 hours of treatment, three months of functional independence, and mortality. Women were significantly older (mean age 71.3 vs 66.2 years; p < 0.01), more often suffered from hypertension (78.3% vs 70.1%; p < 0.01) and cardio-embolic strokes (34.7% vs 27.1%; p < 0.01), and presented heavier baseline deficits. There were no differences in sICH, but after three months fewer women were functionally independent (46.5% vs 53.3%; p < 0.01) and women had higher mortality (26.0% vs 19.7%; p < 0.01). Of the ischaemic stroke patients treated with intravenous thrombolysis, women had worse long-term outcomes than men. This discrepancy may be explained by the older age and higher proportion of cardio-embolic strokes with more severe baseline deficits. However, multiple logistic analysis did not show that sex itself had an impact on the greater mortality in women after a stroke, or on the poorer prognosis.

Stroke in the Middle-East and North Africa: A 2-year prospective observational study of stroke characteristics in the region-Results from the Safe Implementation of Treatments in Stroke (SITS)-Middle-East and North African (MENA).

Stroke incidence and mortality are reported to have increased in the Middle-East and North African (MENA) countries during the last decade. This was a prospective observational study to examine the baseline characteristics of stroke patients in the MENA region and to compare the MENA vs. the non-MENA stroke cohort in the Safe Implementation of Treatments in Stroke (SITS) International Registry. Of the 13,822 patients with ischemic and hemorrhagic stroke enrolled in the SITS-All Patients Protocol between June 2014 and May 2016, 5897 patients (43%) were recruited in MENA. The median onset-to-door time was 5 h (IQR: 2:20-13:00), National Institutes of Health Stroke Scale (NIHSS) score was 8 (4-13) and age was 65 years (56-76). Hypertension (66%) and diabetes (38%) were the prevailing risk factors; large artery stenosis > 50% (25.3%) and lacunar strokes (24.1%) were the most common ischemic stroke etiologies. In comparison, non-MENA countries displayed an onset-to-door time of 5:50 h (2:00-18:45), a median of NIHSS 6 (3-14), and a median age of 66 (56-76), with other large vessel disease and cardiac embolism as the main ischemic stroke etiologies. Hemorrhagic strokes (10%) were less common compared to non-MENA countries (13.9%). In MENA, only a low proportion of patients (21%) was admitted to stroke units. MENA patients are slightly younger, have a higher prevalence of diabetes and slightly more severe ischemic strokes, commonly of atherosclerotic or microvascular etiology. Admission into stroke units and long-term follow-up need to be improved. It is suspected that cardiac embolism and atrial fibrillation are currently underdiagnosed in MENA countries.

Intravenous Thrombolysis for Ischemic Stroke Patients on Dual Antiplatelets.

We assessed the outcomes of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients on dual antiplatelet therapy prior to stroke onset. We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register on consecutive IVT-treated AIS patients during a 7-year period (2010-2017). In propensity score matched groups of patients with dual antiplatelet pretreatment and no antiplatelet pretreatment, we compared: (1) symptomatic intracerebral hemorrhage (SICH), according to SITS Monitoring Study (MOST), European Cooperative Acute Stroke Study (ECASS) II, and National Institute of Neurological Disorders and Stroke (NINDS) definitions; (2) 3-month mortality; (3) 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores = 0-1); (4) 3-month functional independence (FI; mRS scores = 0-2); and (5) distribution of the 3-month mRS scores. Dual antiplatelet pretreatment was defined as all possible combinations among aspirin, clopidogrel, dipyridamole, and any other antiplatelet. Propensity score matching resulted in 2 groups of 1,043 patients each, balanced for all baseline characteristics. In the propensity score matched analysis, the 2 groups had comparable (p > 0.017 using Bonferroni correction for multiple comparisons) SICH rates according to SITS-MOST (2.9% vs 1.5%, 95% confidence interval [CI] = -0.03 to -0.01), ECASS II (5.2% vs 4.4%, 95% CI = -0.03 to 0.01), and NINDS (7.7% vs 6.6%, 95% CI = -0.03 to 0.01) definitions. No differences in the 3-month mortality (17.9% vs 16.6%, 95% CI = -0.05 to 0.02), FFO (45.6% vs 46.0%, 95% CI = -0.04 to 0.05), FI (59.2% vs 60.7%, 95% CI = -0.03 to 0.06), or distribution in 3-month mRS scores (2 [1-4] vs 2 [0-4], 95% CI = -0.29 to 0.09) were documented between the 2 groups. Given that patients on dual antiplatelet pretreatment have similar SICH, 3-month mortality rates, and functional outcomes compared to patients with no antiplatelet pretreatment, dual antiplatelet pretreatment history should not be used as a reason to withhold IVT in otherwise eligible AIS patients. Ann Neurol 2018;83:89-97.

Predictors of symptomatic intracranial haemorrhage in off-label thrombolysis: an analysis of the Safe Implementation of Treatments in Stroke registry.

Intravenous thrombolysis (IVT) is the only approved pharmacological treatment for acute ischemic stroke. Off-label IVT for ischemic stroke is common. We aimed to analyse its safety in a large database. This was a retrospective analysis of the safe implementation of treatments in stroke (SITS) thrombolysis registry with regard to 11 off-label criteria according to the European licence for alteplase. Symptomatic intracranial haemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study (ECASS II) definition and the National Institute of Neurological Disorders and Stroke definition as secondary safety endpoints. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed. Patients from 793 centres in 44 countries were included, mainly (95%) in Europe. A total of 56 258 patients who were treated with intravenous alteplase were included. Median age was 71 (IQR 61-78) years and median National Institutes of Health Stroke Scale score was 12 (IQR 7-17). A total of 16 740 (30%) patients received off-label IVT and 1037 (1.8%) patients suffered from SICH according to the SITS definition (SICH SITS). Median percentage of missing values per variable was 0.4%. The only two off-label criteria constituting independent positive and negative predictors for SICH SITS were high blood pressure (odds ratio, 1.39; 95% confidence interval, 1.08-1.80; P = 0.012) and minor stroke (odds ratio, 0.51; 95% confidence interval, 0.33-0.78; P = 0.002). Very severe stroke, previous stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and National Institute of Neurological Disorders and Stroke definitions. Thrombolysis appears to be safe with regard to SICH for most of the off-label criteria, especially for minor stroke, but is risky in patients with high blood pressure. Individual risk-benefit evaluation should be performed.

Abstract 188: Safety and Efficacy of off-label Intravenous Thrombolysis in Patients With Acute Ischemic Stroke: An Observational Study From the International Safe Implementation of Treatments in Stroke (SITS) Registry

Introduction: Intravenous thrombolysis is the only approved pharmacological treatment for acute ischemic stroke. Due to strict license regulations, off-label treatment is common. We aimed to analyze the safety and efficacy of off-label thrombolysis. Methods: Retrospective analysis of 56258 patients from the Safe Implementation of Treatments in Stroke (SITS) thrombolysis registry was performed regarding 11 off-label criteria according to the European license for alteplase. Symptomatic intracranial hemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study II (ECASS II) definition and the National Institute of Neurological Disorders and Stroke (NINDS) definition as secondary safety endpoints. Favorable outcome, defined as modified Rankin Scale score 3 months after stroke between 0 and 2 was the primary efficacy endpoint. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed for the efficacy and safety endpoints. Results: In total, 16740 (30%) patients received off-label thrombolysis. SICH according to the SITS definition occurred in 1037 (1.8%) patients. The only two off-label criteria constituting independent positive and negative predictors for SICH according to the SITS definition were elevated blood pressure (OR 1.39; p=0.012) and minor stroke (OR 0.51; p=0.002). Very severe stroke, history of stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and NINDS definition. Favorable outcome was found in 24834 patients (54.5%). Independent predictors of favorable outcome comprised of minor stroke (positive predictor) and very severe stroke, history of stroke and diabetes, age and elevated blood pressure (all negative predictors). Inclusion of SICH according to the ECASS II definition in the multivariable analysis did not change the OR of these off-label criteria. Conclusions: Thrombolysis appears to be safe and efficient for most of the off-label criteria. Individual risk-benefit evaluation should be performed before off-label thrombolysis, especially in patients with combinations of these off-label criteria.

Applying openEHR\u2019s Guideline Definition Language to the SITS international stroke treatment registry: a European retrospective observational study

BackgroundInteroperability standards intend to standardise health information, clinical practice guidelines intend to standardise care procedures, and patient data registries are vital for monitoring quality of care and for clinical research. This study combines all three: it uses interoperability specifications to model guideline knowledge and applies the result to registry data.MethodsWe applied the openEHR Guideline Definition Language (GDL) to data from 18,400 European patients in the Safe Implementation of Treatments in Stroke (SITS) registry to retrospectively check their compliance with European recommendations for acute stroke treatment.ResultsComparing compliance rates obtained with GDL to those obtained by conventional statistical data analysis yielded a complete match, suggesting that GDL technology is reliable for guideline compliance checking.ConclusionsThe successful application of a standard guideline formalism to a large patient registry dataset is an important step toward widespread implementation of computer-interpretable guidelines in clinical practice and registry-based research. Application of the methodology gave important results on the evolution of stroke care in Europe, important both for quality of care monitoring and clinical research.

Pharmacotherapy Updates of Recombinant Tissue Plasminogen Activator (r-TPA) in Acute Ischemic Stroke

Context: According to published articles, thrombosis is the main reason for death all over of the world. With stroke time missing is brain missing, therefore, the FDA-approved drug r-TPA, could be administered as initial IV bolus in less than 3 - 4.5 hours from onset of Acute Ischemic Stroke (AIS). The aim of this review was to provide updated pharmacotherapy related to r-TPA in AIS. Evidence Acquisition: Searches for associated published articles were conducted in major databases until September 2015. The main terms used in the search were a combination of words and phrases such as ischemic stroke and tissue plasminogen activator. Results: Age, time of onset, systolic blood pressure, diabetes, stroke severity, co-morbidities and premorbid medical situation, stroke scale according to national institute of health and outcomes related to CT (head, angiogram and perfusion) were considered when determining successful treatment by endovascular thrombectomy. According to the 2015 guidelines, strategies related to successful pharmacotherapy management should be based on class I evidence-care on a stroke unit, IV-r-TPA within 3 - 4.5 hours of stroke onset, aspirin commenced within 48 hours of stroke onset, and decompressive cranioctomy for supratentorial malignant hemispheric cerebral infarction. Hemorrhagic stroke (intraparenchymal, subarachnoid, intraventricular, intracerebral such as orolingual angioedema), hematoma(epidural and subdural) and head trauma are the absolute contraindications related to r-TPA prescription. Conclusions: Due to considerable inter- and intra- heterogeneity among studies performed by other centers such as differences in study project, background, and population features, determining a pharmacotherapy model based on Safe Implementation of Treatments in stroke or SITS seem advantageous.

Alteplase

Alteplase

Organizational changes aiming to reduce iv tPA door-to-needle time

To assess time trends in intravenous thrombolytic (iv tPA) treatment in a general local hospital during a period with organizational changes, especially how movement of treatment start from the emergency room (ER) to the CT laboratory, and changing method of administration of acute antihypertensive medication influenced on door-to-needle time (DNT). All stroke patients treated with iv tPA have been prospectively enrolled in the Safe Implementation of Treatments in Stroke (SITS) registry. Data from 2007 to 2011 were reviewed. Safety was evaluated by the incidence of symptomatic intracerebral hemorrhage (SICH). Predictors of DNT were assessed by multivariable regression. Two hundred and forty-three patients were treated with iv tPA. The annual treatment rate reached 21.9% of patients with ischemic strokes admitted to the hospital. Median DNT decreased from 36 to 28 min (P ≤ 0.001). The incidence of SICH remained low and was throughout the period 2.5%. Treatment start in the CT laboratory vs in the ER was associated with a reduction in median DNT (P = 0.007). Acute antihypertensive treatment and treatment with warfarin were associated with increased DNT (P = 0.024 and P = 0.003, respectively). Age, gender, baseline NIHSS, onset-to-door time, comorbidity, and method of administration of acute antihypertensive treatment did not influence DNT significantly. Streamlining of iv tPA logistics can reduce median DNT to <30 min in a general local hospital. Moving treatment start from the ER to the CT laboratory contributed to reduce DNT. Our organizational model was resistant to influence on DNT by patient age, gender, stroke severity, and time to hospital arrival. The incidence of SICH remained low.

Thrombolysis in acute ischaemic stroke: Initial experience in a general hospital in a developing country

Background: The aim of the study was to present our initial experience with the use of intravenous thrombolytic therapy in patients with acute ischaemic stroke. We present results related to demography, time, and/INS; data on the clinical outcome of patients and compare the results with other studies (Serbian Experience with Thrombolysis in Ischemic Stroke (SETIS) and Safe Implementation of Treatments in Stroke (SITS)).

Predicting the Risk of Symptomatic Intracerebral Hemorrhage in Ischemic Stroke Treated With Intravenous Alteplase

Symptomatic intracerebral hemorrhage (SICH) is a serious complication in patients with acute ischemic stroke treated with intravenous thrombolysis. We aimed to develop a clinical score that can easily be applied to predict the risk of SICH. We analyzed data from 31 627 patients treated with intravenous alteplase enrolled in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register. The outcome measure was SICH per the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) definition: a Type 2 parenchymal hemorrhage with deterioration in National Institutes of Health Stroke Scale score of ≥ 4 points or death. Univariate risk factors associated with the outcome were entered into a logistic regression model after stratification of continuous variables. Adjusted ORs for the independent risk factors were converted into points, which were summated to produce a risk score. We identified 9 independent risk factors for SICH: baseline National Institutes of Health Stroke Scale, serum glucose, systolic blood pressure, age, body weight, stroke onset to treatment time, aspirin or combined aspirin and clopidogrel, and history of hypertension. The overall rate of SICH was 1.8%. The risk score ranged from 0 to 12 points and showed a >70-fold graded increase in the rate of SICH for patients with a score ≥ 10 points (14.3%) compared with a score of 0 point (0.2%). The prognostic discriminating capability by C statistic was 0.70. The SITS SICH risk score predicts large cerebral parenchymal hemorrhages associated with severe clinical deterioration. The score could aid clinicians to identify patients at high as well as low risk of SICH after intravenous alteplase.

Abstract 3338: Marked Increase in Proportion of Patients over 80 years Treated with iv Thrombolysis and Registered in SITS (Safe Implementation of Treatments in Stroke) Coincides with Publications

Objectives . A prompt increase in patients treated in the extended time window 3-4.5 h after stroke onset was noted in the SITS registry after publication of the results of ECASS III (NEJM 2008) and the SITS-ISTR 3-4.5 h cohort (Lancet 2008). Within a few months the proportion increased from around 7% to a plateau of 20%. In November 2010, three studies were published describing SITS and VISTA (Virtual International Stroke Trials Archive) data on safety and efficacy of i.v. thrombolysis in the elderly population (Mishra et al, Stroke 2010, Ford et al, Stroke 2010; Mishra et al, BMJ 2010). We tested for a similarly rapid response to the publications of results in the elderly . Methods: Between 1 st January 2007 and 30 th June 2011, 36,753 patients treated with i.v. thrombolysis were registered in SITS, of whom 4,458 were over 80 years (12.1%). We examined the quarterly rates and 95% confidence intervals of patients over age 80 treated with i.v. thrombolysis. Since all 3 studies were published around November 2010, we compared the rates in the intervals Q1 2007-Q3 2010 and Q4 2010- Q2 2011. Results: The proportion of elderly (over 80 years) was 11.1 % (95% CI 10.8-11.5) across Q1 2007 to Q3 2010, From Q4 2010 to Q2 2011 it increased to 17.5 %, (95% CI 16.5-18.5, (p&lt;0.0001). The proportions during 2010 Q1-Q3 were 10.6%, 11.9%, 11.3% (pre-publication) and during 2010 Q4 to 2011Q216.9%, 16.4% and 19.3% (post-publication). Conclusions: A statistically significant increase in the proportion of elderly treated with i.v. thrombolysis was observed from the fourth quarter of 2010. The relative increase approached 60% and coincided with three publications of safety and efficacy of i.v. thrombolysis in the elderly based on VISTA and SITS data. Our observations suggest a rapid implementation of new data by the medical community and underline the value of analyses of observational data from SITS and VISTA for the very elderly who were excluded or under-represented in the key clinical trials.

Systemic thrombolytic therapy in acute ischemic stroke — New experiences in spreading network of stroke units in Croatia

BackgroundThe aims of this paper are: 1) to present the data of systemic thrombolysis for ischemic stroke in five Croatian centers from July 2008 till January 2010; 2) to compare the results between centers and; 3) to compare data with previously published results from 2006 to 2008 period from our center, and with the data from SITS (Safe Implementation of Treatments in Stroke). MethodsWe retrospectively reviewed the medical data of thrombolysed patients in following hospitals: University Hospital Center Zagreb (91 patients), University Hospital Split (25 patients), University Hospital Osijek (22 patients), General Hospital Varaždin (21 patient), and General Hospital Zadar (7 patients). ResultsThe “time to door” for all centers was 79.71±38.63min, the “door to needle” period was 64.39±24.18min. Systolic and diastolic blood pressures at admission were 158.65±27.72 and 90.18±15.03mm Hg, respectively. Systolic and diastolic blood pressures measured immediately prior to administering rt-PA were 152.19±23.17 and 85.40±15.27mm Hg, respectively. Initial median NIHSS score was 12, median NIHSS 2h post thrombolysis was 8, and 7th day after rt-PA treatment 4. Intracerebral hemorrhages or secondary hemorrhagic transformations occurred in 21 (12.65%) patients, among which nine were symptomatic. In a 4.5h time window total of 17 patients were thrombolysed. We did not find any differences in outcome between this group and group of patients thrombolysed in the 3h time-window. The group of patients older than 80years had a worse outcome. ConclusionsAccording to our data, treatment with rt-PA is safe, feasible and effective for stroke patients in both university as well as regional hospitals having stroke units established. Organization of stroke units in regional hospitals, as well as systematic education of public health workers and neurologists, leads to the possibility for each patient to reach the nearest stroke unit and gets the thrombolytic therapy in the therapeutic time window.