Safety and Efficacy of Baseline Antiplatelet Treatment in Patients Undergoing Mechanical Thrombectomy for Ischemic Stroke: Antiplatelets Before Mechanical Thrombectomy.

PURPOSE: To investigate the safety and efficacy of baseline antiplatelet treatment in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT). MATERIALS AND METHODS: Baseline use of antiplatelet medication before MT for (AIS) may provide benefit on reperfusion and clinical outcome but could also carry an increased risk of intracranial hemorrhage (ICH). All consecutive patients with AIS and treated with MT with and without intravenous thrombolysis (IVT) between January 2012 and December 2019 in all centers performing MT nationwide were reviewed. Data were prospectively collected in national registries (eg, SITS-TBY and RES-Q). Primary outcome was functional independence (modified Rankin Scale 0-2) at 3 months; secondary outcome was ICH. RESULTS: Of the 4,351 patients who underwent MT, 1,750 (40%) and 666 (15%) were excluded owing to missing data from the functional independence and ICH outcome cohorts, respectively. In the functional independence cohort (n = 2,601), 771 (30%) patients received antiplatelets before MT. Favorable outcome did not differ in any antiplatelet, aspirin, and clopidogrel groups when compared with that in the no-antiplatelet group: odds ratio (OR), 1.00 (95% CI, 0.84-1.20); OR, 1.05 (95% CI, 0.86-1.27); and OR, 0.88 (95% CI, 0.55-1.41), respectively. In the ICH cohort (n = 3,685), 1095 (30%) patients received antiplatelets before MT. The rates of ICH did not increase in any treatment options (any antiplatelet, aspirin, clopidogrel, and dual antiplatelet groups) when compared with those in the no-antiplatelet group: OR, 1.03 (95% CI, 0.87-1.21); OR, 0.99 (95% CI, 0.83-1.18); OR, 1.10 (95% CI, 0.82-1.47); and OR, 1.43 (95% CI, 0.87-2.33), respectively. CONCLUSIONS: Antiplatelet monotherapy before MT did not improve functional independence or increase the risk of ICH.

Association of statin pre-treatment with baseline stroke severity and outcome in patients with acute ischemic stroke and received reperfusion treatment: An observational study.

BACKGROUND: Statins have an important role in stroke prevention, especially in high-risk populations and may also affect the initial stroke severity and outcomes in patients taking them before an ischemic stroke. AIMS: Our aim was to evaluate the association of statin pre-treatment with the severity in acute ischemic stroke (AIS). METHODS: We analyzed AIS patients received intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT) and recorded in the SITS International Thrombolysis and Thrombectomy Registry from 2011 to 2017. We identified patients with statin information at baseline. The primary outcome was baseline National Institutes of Health Stroke Scale (NIHSS) score. Secondary outcomes were NIHSS score at 24 h, symptomatic intracerebral hemorrhage (SICH) and functional outcome at 90 days after acute intervention. Multivariable linear and logistic regression and propensity score matching (PSM) was used to quantify the effect of statin pre-treatment. RESULTS: Of 93,849 patients, 23,651 (25.2%) were treated with statins prior the AIS. Statin pre-treatment group was older and had higher comorbidity. Median NIHSS at baseline was similar between groups. In the adjusted and PSM analysis, statin pre-treatment was inversely associated with baseline NIHSS (odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.6-0.99 and OR for PSM 0.73, 95% CI = 0.54-0.99, p = 0.004) and independently associated with mild stroke defined as NIHSS ⩽8 in adjusted and PSM analysis (OR = 1.21, 95% CI = 1.1-1.34, p < 0.001 and OR for PSM 1.17, 95% CI = 1.05-1.31, p = 0.007). Regarding secondary outcomes, there were no differences in functional outcomes, death nor SICH rates between groups. CONCLUSION: Prior treatment with statins was associated with lower NIHSS at baseline. However, this association did not translate into any difference regarding functional outcome at 90 days. No association was found regarding SICH. These findings indicate the need of further studies to assess the effect on statin pre-treatment on initial stroke severity.

Ultrashort Door-to-Needle Time for Intravenous Thrombolysis Is Safer and Improves Outcome in the Czech Republic: Nationwide Study 2004 to 2019.

Background The benefit of intravenous thrombolysis is time dependent. It remains unclear, however, whether dramatic shortening of door-to-needle time (DNT) among different types of hospitals nationwide does not compromise safety and still improves outcome. Methods and Results Multifaceted intervention to shorten DNT was introduced at a national level, and prospectively collected data from a registry between 2004 and 2019 were analyzed. Generalized estimating equation was used to identify the association between DNT and outcomes independently from prespecified baseline variables. The primary outcome was modified Rankin score 0 to 1 at 3 months, and secondary outcomes were parenchymal hemorrhage/intracerebral hemorrhage (ICH), any ICH, and death. Of 31 316 patients treated with intravenous thrombolysis alone, 18 861 (60%) had available data: age 70±13 years, National Institutes of Health Stroke Scale at baseline (median, 8; interquartile range, 5-14), and 45% men. DNT groups 0 to 20 minutes, 21 to 40 minutes, 41 to 60 minutes, and >60 minutes had 3536 (19%), 5333 (28%), 4856 (26%), and 5136 (27%) patients. National median DNT dropped from 74 minutes in 2004 to 22 minutes in 2019. Shorter DNT had proportional benefit: it increased the odds of achieving modified Rankin score 0 to 1 and decreased the odds of parenchymal hemorrhage/ICH, any ICH, and mortality. Patients with DNT ≤20 minutes, 21 to 40 minutes, and 41 to 60 minutes as compared with DNT >60 minutes had adjusted odds ratios for modified Rankin score 0 to 1 of the following: 1.30 (95% CI, 1.12-1.51), 1.33 (95% CI, 1.15-1.54), and 1.15 (95% CI, 1.02-1.29), and for parenchymal hemorrhage/ICH: 0.57 (95% CI, 0.45-0.71), 0.76 (95% CI, 0.61-0.94), 0.83 (95% CI, 0.70-0.99), respectively. Conclusions Ultrashort initiation of thrombolysis is feasible, improves outcome, and makes treatments safer because of fewer intracerebral hemorrhages. Stroke management should be optimized to initiate thrombolysis as soon as possible optimally within 20 minutes from arrival to a hospital.

Stroke 20 20: Implementation goals for intravenous thrombolysis.

INTRODUCTION: Knowledge of the implementation gap would facilitate the use of intravenous thrombolysis in stroke, which is still low in many countries. The study was conducted to identify national implementation targets for the utilisation and logistics of intravenous thrombolysis. MATERIAL AND METHOD: Multicomponent interventions by stakeholders in health care to optimise prehospital and hospital management with the goal of fast and accessible intravenous thrombolysis for every candidate. Implementation results were documented from prospectively collected cases in all 45 stroke centres nationally. The thrombolytic rate was calculated from the total number of all ischemic strokes in the population of the Czech Republic since 2004. RESULTS: Thrombolytic rates of 1.3 (95%CI 1.1 to 1.4), 5.4 (95%CI 5.1 to 5.7), 13.6 (95%CI 13.1 to 14.0), 23.3 (95%CI 22.8 to 23.9), and 23.5% (95%CI 23.0 to 24.1%) were achieved in 2005, 2009, 2014, 2017, and 2018, respectively. National median door-to-needle times were 60-70 minutes before 2012 and then decreased progressively every year to 25 minutes (IQR 17 to 36) in 2018. In 2018, 33% of both university and non-university hospitals achieved median door-to-needle time ≤20 minutes. In 2018, door-to-needle times ≤20, ≤45, and ≤60 minutes were achieved in 39, 85, and 93% of patients. DISCUSSION: Thrombolysis can be provided to ≥ 20% of all ischemic strokes nationwide and it is realistic to achieve median door-to-needle time 20 minutes. CONCLUSION: Stroke 20-20 could serve as national implementation target for intravenous thrombolysis and country specific implementation policies should be applied to achieve such target.

Role of blood biomarkers in spontaneous intracerebral hemorrhage - a prospectively studied cohort of patients.

The study of blood biomarkers can offer new possibilities in diagnostics, prognostication, determination of etiology, and management of spontaneous intracerebral hemorrhage. The aim of our study was to assess the relationship between a panel of selected blood biomarkers and clinical and radiodiagnostic parameters in patients with spontaneous intracerebral hemorrhage. Primarily, the aim was to find a prognostic biomarker which could help in deciding on the optimal categorization of treatment. A total of 70 patients were prospectively included in this study. As shown by our findings, higher levels of S100B protein are associated with larger hematoma volume. They predict hematoma progression and an unfavorable outcome. One other positive correlation was found between hematoma volume and interleukin 6, interleukin 10 and blood glucose. Lower levels of matrix metalloproteinase 9 are an independent prognostic factor for hematoma progression in patients with spontaneous intracerebral hemorrhage.

Thrombectomy vs medical management in low NIHSS acute anterior circulation stroke.

OBJECTIVE: To undertake an effectiveness and safety analysis of EVT in patients with LVO and NIH Stroke Scale (NIHSS) score ≤6 using datasets of multicenter and multinational nature. METHODS: We pooled patients with anterior circulation occlusion from 3 prospective international cohorts. Patients were eligible if presentation occurred within 12 hours from last known well and baseline NIHSS ≤6. Primary outcome was modified Rankin Scale (mRS) score 0-1 at 90 days. Secondary outcomes included neurologic deterioration at 24 hours (change in NIHSS of ≥2 points), mRS 0-2 at 90 days, and 90-day all-cause mortality. We used propensity score matching to adjust for nonrandomized treatment allocation. RESULTS: Among 236 patients who fit inclusion criteria, 139 received EVT and 97 received medical management. Compared to medical management, the EVT group was younger (65 vs 72 years; p < 0.001), had more proximal occlusions (p < 0.001), and less frequently received concurrent IV thrombolysis (57.7% vs 71.2%; p = 0.04). After propensity score matching, clinical outcomes between the 2 groups were not significantly different. EVT patients had an 8.6% (95% confidence interval [CI] -8.8% to 26.1%) higher rate of excellent 90-day outcome, despite a 22.3% (95% CI, 3.0%-41.6%) higher risk of neurologic deterioration at 24 hours. CONCLUSIONS: EVT for LVO in patients with low NIHSS score was associated with increased risk of neurologic deterioration at 24 hours. However, both EVT and medical management resulted in similar proportions of excellent clinical outcomes at 90 days. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with acute anterior circulation ischemic strokes and LVO with NIHSS < 6, EVT and medical management result in similar outcomes at 90 days.

The Incidence and Associated Factors of Early Neurological Deterioration After Thrombolysis: Results From SITS Registry.

BACKGROUND AND PURPOSE: Early neurological deterioration (END) after stroke onset may predict severe outcomes. Estimated rates of END after intravenous thrombolysis among small patient samples have been reported up to 29.8%. We studied the incidence and factors associated with END among patients following intravenous thrombolysis. METHODS: We analyzed SITS-International Stroke Thrombolysis registry patients with known outcomes enrolled in 2010 to 2017. END was defined as an increase in National Institutes of Health Stroke Scale score ≥4 or death within 24 hours from baseline National Institutes of Health Stroke Scale. We determined the incidence of END and used logistic regression models to inspect its associated factors. We adjusted for variables found significant in univariate analyses (P<0.05). Main outcomes were incidence of END, associated predictors of END, ordinal day-90 mRS, and day-90 mortality. RESULTS: We excluded 53 539 patients and included 50 726 patients. The incidence of END was 3415/50 726 (6.7% [95% CI, 6.5%-7.0%]). Factors independently associated with END on multivariate analysis were intracerebral hemorrhage (OR, 3.23 [95% CI, 2.96-3.54], P<0.001), large vessel disease (LVD) with carotid stenosis (OR, 2.97 [95% CI, 2.45-3.61], P<0.001), other LVD (OR, 2.41 [95% CI, 2.03-2.88], P<0.001), and ischemic stroke versus transient ischemic attack (TIA)/stroke mimics (OR, 16.14 [95% CI, 3.99-65.3], P<0.001). END was associated with worse outcome on ordinal mRS: adjusted OR 2.48 (95% CI, 2.39-2.57, P<0.001) by day-90 compared with no END. The adjusted OR for day-90 mortality was 9.70 (95% CI, 8.36-11.26, P<0.001). CONCLUSIONS: The routinely observed rate of END reflected by real-world data is low, but END greatly increases risk of disability and mortality. Readily identifiable factors predict END and may help with understanding causal mechanisms to assist prevention of END.

Association of Baseline Hyperglycemia With Outcomes of Patients With and Without Diabetes With Acute Ischemic Stroke Treated With Intravenous Thrombolysis: A Propensity Score-Matched Analysis From the SITS-ISTR Registry.

Available data from observational studies on the association of admission hyperglycemia (aHG) with outcomes of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) are contradictory, especially when stratified by diabetes mellitus (DM) history. We assessed the association of aHG (≥144 mg/dL) with outcomes stratified by DM history using propensity score-matched (PSM) data from the SITS-ISTR. The primary safety outcome was symptomatic intracranial hemorrhage (SICH); 3-month functional independence (FI) (modified Rankin Scale [mRS] scores 0-2) represented the primary efficacy outcome. Patients with and without aHG did not differ in baseline characteristics both in the non-DM (n = 12,318) and DM (n = 6,572) PSM subgroups. In the non-DM group, patients with aHG had lower 3-month FI rates (53.3% vs. 57.9%, P < 0.001), higher 3-month mortality rates (19.2% vs. 16.0%, P < 0.001), and similar symptomatic intracerebral hemorrhage (SICH) rates (1.7% vs. 1.8%, P = 0.563) compared with patients without aHG. Similarly, in the DM group, patients with aHG had lower rates of 3-month favorable functional outcome (mRS scores 0-1, 34.1% vs. 39.3%, P < 0.001) and FI (48.2% vs. 52.5%, P < 0.001), higher 3-month mortality rates (23.7% vs. 19.9%, P < 0.001), and similar SICH rates (2.2% vs. 2.7%, P = 0.224) compared with patients without aHG. In conclusion, aHG was associated with unfavorable 3-month clinical outcomes in patients with and without DM and AIS treated with IVT.

Mechanical thrombectomy performs similarly in real world practice: a 2016 nationwide study from the Czech Republic.

BACKGROUND: Randomized clinical trials have proven mechanical thrombectomy (MT) to be a highly effective and safe treatment in acute stroke. The purpose of this study was to compare neurothrombectomy data from the Czech Republic (CR) with data from the HERMES meta-analysis. METHODS: Available nationwide data for the CR from 2016 from the Safe Implementation of Treatments in Stroke-Thrombectomy (SITS-TBY) registry for patients with terminal internal carotid artery (ICA) and/or middle cerebral artery (MCA) occlusions were compared with data from HERMES. CR and HERMES patients were comparable in age, sex, and baseline National Institutes of Health Stroke Scale scores. RESULTS: From a total of 1053 MTs performed in the CR, 845 (80%) were reported in the SITS-TBY. From these, 604 (72%) were included in this study. Occlusion locations were as follows (CR vs HERMES): ICA 22% versus 21% (P=0.16), M1 MCA 62% versus 69% (P=0.004), and M2 MCA 16% versus 8% (P<0.0001). Intravenous thrombolysis was given to 76% versus 83% of patients, respectively (P=0.003). Median onset to reperfusion times were comparable: 232 versus 285 min, respectively (P=0.66). A modified Thrombolysis in Cerebral Infarction score of 2b/3 was achieved in 74% (433/584) versus 71% (390/549) of patients, respectively (OR 1.17, 95% CI 0.90-1.5, P=0.24). There was no statistically significant difference in the percentage of parenchymalhematoma type 2 (OR 1.12, 95% CI 0.66-1.90, P=0.68). A modified Rankin Scale score of 0-2 at 3 months was achieved in 48% (184/268) versus 46% (291/633) of patients, respectively (OR 0.92, 95% CI 0.71-1.18, P=0.48). CONCLUSIONS: Data on efficacy, safety, and logistics of MT from the CR were similar to data from the HERMES collaboration.

Prolonged Corrected QT Interval as a Predictor of Clinical Outcome in Acute Ischemic Stroke.

BACKGROUND: This study aimed to investigate changes of corrected QT (QTc) interval during acute ischemic stroke and its correlation with high-sensitivity troponin I (hsTnI), brain natriuretic peptide (BNP), neurological outcome, and 1-year mortality. METHODS: We registered electrocardiogram in 69 patients immediately after admission to the intensive care unit and then after 24 and 48 hours. Computed tomography was performed on admission to determine brain infarct size and localization. Neurological outcome was assessed by modified Rankin scale (mRS) at discharge. RESULTS: Forty-five (65.2%) patients had prolonged QTc at baseline; only 18 (26.1%) patients had prolonged QTc after 48 hours. Baseline QTc was not associated with neurological outcome (P = .27). However, prolonged QTc after 48 hours was associated with worse mRS at discharge (4.5 [4.0-6.0] versus 2.0 [1.0-3.0]; P < .0001). Patients who deceased during hospitalization (n = 7 [10.1%]) as compared with survivors had more frequently prolonged QTc after 48 hours (38.9 versus 0%; P < .0001), higher level of hsTnI (48.4 [36.1-75.0] versus 8.6 [3.4-26.5]; P = .003), and BNP (334 [224-866] versus 109 [30-190]; P = .014). In univariate analysis, 1-year mortality was associated with prolonged QTc after 48 hours, hsTnI, and BNP. In multivariate analysis, only BNP remained to be associated with 1-year mortality (odds ratio 3.41, 95% confidence interval 1.06-11.03). CONCLUSIONS: QTc interval in patients with acute ischemic stroke is a dynamic parameter. Prolonged QTc after 48 hours, but not baseline QTc, correlated with neurological outcome and 1-year mortality. Patients with prolonged QTc had higher level of hsTnI.

Length of occlusion predicts recanalization and outcome after intravenous thrombolysis in middle cerebral artery stroke.

BACKGROUND AND PURPOSE: The length of large vessel occlusion is considered a major factor for therapy in patients with ischemic stroke. We used 4D-CT angiography evaluation of middle cerebral artery occlusion in prediction of recanalization and favorable clinical outcome and after intravenous thrombolysis (IV-tPA). METHODS: In 80 patients treated with IV-tPA for acute complete middle cerebral artery/M1 occlusion determined using CT angiography and temporal maximum intensity projection, calculated from 4D-CT angiography, the length of middle cerebral artery proximal stump, occlusion in M1 or M1 and M2 segment were measured. Univariate and multivariate analyses were performed to define independent predictors of successful recanalization after 24 hours and favorable outcome after 3 months. RESULTS: The length of occlusion was measureable in all patients using temporal maximum intensity projection. Recanalization thrombolysis in myocardial infarction 2 to 3 was achieved in 37 individuals (46%). The extension to M2 segment as a category (odds ratio, 4.58; 95% confidence interval, 1.39-15.05; P=0.012) and the length of M1 segment occlusion (odds ratio, 0.82; 95% confidence interval, 0.73-0.92; P=0.0007) with an optimal cutoff value of 12 mm (sensitivity 0.67; specificity 0.71) were significant independent predictors of recanalization. Favorable outcome (modified Rankin scale 0-2) was achieved in 25 patients (31%), baseline National Institutes of Health Stroke Scale (odds ratio, 0.82; 95% confidence interval, 0.72-0.93; P=0.003) and the length of occlusion M1 in segment (odds ratio, 0.79; 95% confidence interval, 0.69-0.91; P=0.0008) with an optimal cutoff value of 11 mm (sensitivity 0.74; specificity 0.76) were significant independent predictors of favorable outcome. CONCLUSIONS: The length of middle cerebral artery occlusion is an independent predictor of successful IV-tPA treatment.

Personalized approach to primary and secondary prevention of ischemic stroke.

Primary and secondary prevention of ischemic stroke represents a significant part of stroke management and health care. Although there are official guidelines concerning stroke management, new knowledge are introduced to them with a slight delay. This article provides an overview of current information on primary and secondary prevention of ischemic stroke. It summarizes information especially in the field of cardioembolic stroke, the use of new anticoagulants and the management of carotid stenosis based on the results of recent clinical studies. The optimal approach in stroke management is to follow these recommendations, to know new strategies and to apply an individual personalized approach in our clinical decisions.

Within-day and weekly variations of thrombolysis in acute ischemic stroke: results from safe implementation of treatments in stroke-international stroke thrombolysis register.

BACKGROUND AND PURPOSE: Temporal variations of thrombolysis delivery and their influence on outcome have been reported with controversial results. In this large cohort study, we evaluated whether thrombolytic treatment has a within-day and weekly variability corresponding to circadian and weekly patterns of ischemic stroke onset, and whether these have impact on clinical outcome. METHODS: We retrospectively analyzed patients with acute ischemic stroke receiving intravenous alteplase, prospectively included in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register. Patients were grouped by treatment on day hours (08:00-19:59) or night hours (20:00-07:59) and treatment on weekdays and weekends. For each subgroup, we analyzed frequency of thrombolytic treatments, time intervals, and outcomes (3-month modified Rankin Scale score 0-2 as good functional outcome, mortality, symptomatic intracerebral hemorrhage). RESULTS: We included 21 513 patients. Considering the mean expected number of patients treated per hour (0.4) and per day of the week (9.8), if no temporal variations were present, patients were significantly treated more during day hours and weekdays (P<0.0001). Median door-to-needle and onset-to-treatment times were longer for patients treated during night hours and on weekends (P<0.01). After adjustment for confounding variables, treatment during day hours was an independent predictor of good functional outcome (odds ratio, 1.12; 95% confidence interval, 1.04-1.21; P=0.004), and patients treated during weekdays were at risk of higher mortality (odds ratio, 1.15; 95% confidence interval, 1.04-1.28; P=0.008). CONCLUSIONS: Frequency of thrombolytic treatment seems to follow the same circadian pattern of stroke incidence, whereas its correspondence to a weekly pattern is less clear. Time of treatment is an independent predictor of outcome.