Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase.

BACKGROUND: Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase). METHODS: AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg) in acute ischemic stroke within 4.5 hours of onset. In this post hoc analysis, baseline characteristics, workflow times, successful reperfusion (extended Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracerebral hemorrhage, 90-day functional independence (modified Rankin Scale score, 0-1), and 90-day mortality were compared by sex. Mixed-effects regression analysis was used adjusting for age, stroke severity, and occlusion site for outcomes. RESULTS: Of 1577 patients treated with intravenous thrombolysis (2019-2022), 755 (47.9%) were women. Women were older (median, 77 [68-86] years in women versus 70 [59-79] years in men) and had a higher proportion of severe strokes (National Institutes of Health Stroke Scale score >15; 32.4% versus 24.9%) and large vessel occlusions (28.7% versus 21.5%) compared with men. All workflow times were comparable between sexes. Women were less likely to achieve functional independence (31.7% versus 39.8%; unadjusted relative risk, 0.80 [95% CI, 0.70-0.91]) and had higher mortality (17.7% versus 13.3%; unadjusted relative risk, 1.33 [95% CI, 1.06-1.69]). Adjusted analysis showed no difference in outcomes between sexes. CONCLUSIONS: Differences in prognostic factors of age, stroke severity, and occlusion site largely accounted for higher functional dependence and mortality in women. No sex disparities were apparent in workflow quality indicators. Given the integration of the AcT trial into clinical practice, these results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Canadian centers. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial.

BACKGROUND: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known; however, the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase. METHODS: Patients included were from AcT, a pragmatic, registry-linked, phase 3 randomized controlled trial comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4.5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin Scale score 0 to 1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage and 90-day mortality rates. Mixed-effects logistic regression was used to assess the following: (a) the association of stroke symptom onset to needle time; (b) door (hospital arrival) to needle time with outcomes; and (c) if these associations were modified by type of thrombolytic administered (tenecteplase versus alteplase), after adjusting for age, sex, baseline stroke severity, and site of intracranial occlusion. RESULTS: Of the 1538 patients included in this analysis, 1146 (74.5%; 591 tenecteplase and 555 alteplase) presented within 3 hours versus 392 (25.5%; 196: TNK and 196 alteplase) who presented within 3 to 4.5 hours of symptom onset. Baseline patient characteristics in the 0 to 3 hours versus 3- to 4.5-hour time window were similar, except patients in the 3- to 4.5-hour window had lower median baseline National Institutes of Health Stroke Severity Scale (10 versus 7, respectively) and lower proportion of patients with large vessel occlusion on baseline CT angiography (26.9% versus 18.7%, respectively). Type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time (Pinteraction=0.161) or door-to-needle time (Pinteraction=0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase while every 10 minutes reduction in door-to-needle time was associated with a 0.2% increase in the probability of achieving 90-day modified Rankin Scale score 0 to 1, respectively. CONCLUSIONS: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes. REGISTRATION: URL: https://classic. CLINICALTRIALS: gov; Unique identifier: NCT03889249.

Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial.

BACKGROUND: Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care. METHODS: In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual. FINDINGS: Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis. FUNDING: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Mortality After Total Anterior Circulation Stroke: A 25-Year Observational Study.

BACKGROUND: Mortality remains a substantial problem after acute ischemic stroke, despite advances in acute stroke treatment over the past three decades. Mortality is particularly high among patients with Total Anterior Circulation Stroke (TACS), generally representing patients with middle cerebral artery occlusions. Notably however, these patients also stand to benefit most from new therapies including endovascular thrombectomy (EVT). In this study, we aimed to examine temporal trends in, and factors associated with, 30-day in-hospital mortality after TACS. METHODS: Information on all patients with community-onset TACS from 1994 through 2019 was extracted from a prospective acute stroke registry. Multivariate analysis was performed on the primary outcome of 30-day in-hospital mortality, as well as secondary functional outcomes. RESULTS: We studied 1106 patients hospitalized for community-onset TACS, 456 (41%) of whom experienced 30-day in-hospital mortality. Over the 25 years of observation, 30-day in-hospital mortality rose and then fell. Increased odds of mortality was associated with age and stroke severity. Decreased odds of mortality was associated with alteplase therapy and EVT, as well as presentation to hospital more than 12 hours after stroke onset. Treatment with alteplase, EVT, or both was associated with higher odds of functional independence and discharge home, and shorter lengths of stay in acute care. CONCLUSIONS: Patients receiving alteplase, EVT, or both had lower 30-day in-hospital mortality and better functional outcomes than those who were untreated. These observational data demonstrate the benefits of recanalization therapy in routine clinical practice.

Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke Update 2020.

The 2020 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for the Secondary Prevention of Stroke includes current evidence-based recommendations and expert opinions intended for use by clinicians across a broad range of settings. They provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations address triage, diagnostic testing, lifestyle behaviors, vaping, hypertension, hyperlipidemia, diabetes, atrial fibrillation, other cardiac conditions, antiplatelet and anticoagulant therapies, and carotid and vertebral artery disease. This update of the previous 2017 guideline contains several new or revised recommendations. Recommendations regarding triage and initial assessment of acute transient ischemic attack (TIA) and minor stroke have been simplified, and selected aspects of the etiological stroke workup are revised. Updated treatment recommendations based on new evidence have been made for dual antiplatelet therapy for TIA and minor stroke; anticoagulant therapy for atrial fibrillation; embolic strokes of undetermined source; low-density lipoprotein lowering; hypertriglyceridemia; diabetes treatment; and patent foramen ovale management. A new section has been added to provide practical guidance regarding temporary interruption of antithrombotic therapy for surgical procedures. Cancer-associated ischemic stroke is addressed. A section on virtual care delivery of secondary stroke prevention services in included to highlight a shifting paradigm of care delivery made more urgent by the global pandemic. In addition, where appropriate, sex differences as they pertain to treatments have been addressed. The CSBPR include supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

Redefining Hematoma Expansion With the Inclusion of Intraventricular Hemorrhage Growth.

Background and Purpose- Definitions of significant hematoma expansion traditionally focus on changes in intraparenchymal volume. The presence of intraventricular hemorrhage (IVH) is a predictor of poor outcome, but current definitions of hematoma expansion do not include IVH expansion. We evaluated whether including IVH expansion to current definitions of hematoma expansion improves the ability to predict 90-day outcome. Methods- Using data from the PREDICT-ICH study (Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT), we compared a standard definition of hematoma expansion (≥6 mL or ≥33%) to revised definitions that includes new IVH development or expansion (≥6 mL or ≥33% or any IVH; ≥6 mL or ≥33% or IVH expansion ≥1 mL). The primary outcome was poor clinical outcome (modified Rankin Scale score, 4-6) at 90 days. Diagnostic accuracy measures were calculated for each definition, and C statistics for each definition were compared using nonparametric methods. Results- Of the 256 patients eligible for primary analysis, 127 (49.6%) had a modified Rankin Scale score of 4 to 6. Sensitivity and specificity for the standard definition (n=80) were 45.7% (95% CI, 36.8-54.7) and 82.9% (95% CI, 75.3-88.9), respectively. The revised definition, ≥6 mL or ≥33% or any IVH (n=113), possessed a sensitivity of 63.8% (95% CI, 54.8-72.1) and specificity of 75.2% (95% CI, 66.8-82.4). Overall accuracy was significantly improved with the revised definition (P=0.013) and after adjusting for relevant covariates, was associated with a 2.55-fold increased odds (95% CI, 1.31-4.94) of poor outcome at 90 days. A second revised definition, ≥6 mL or ≥33% or IVH expansion ≥1 mL, performed similarly (sensitivity, 56.7% [95% CI, 47.6-65.5]; specificity, 78.3% [95% CI, 40.2-85.1]; aOR, 2.40 [95% CI, 1.23-4.69]). Conclusions- In patients with mild-to-moderate ICH, including IVH expansion to the definition of hematoma expansion improves sensitivity with only minimal decreases to specificity and improves overall prediction of 90-day outcome.

Independent Validation of the Hematoma Expansion Prediction Score: A Non-contrast Score Equivalent in Accuracy to the Spot Sign.

BACKGROUND AND PURPOSE: The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign. METHODS: We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression. RESULTS: A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01-1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57-0.71). Youden's method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09-3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61-5.42) were similar to HEP scores ≥ 4. CONCLUSION: The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.

Lack of Early Improvement Predicts Poor Outcome Following Acute Intracerebral Hemorrhage.

OBJECTIVES: There are limited data as to what degree of early neurologic change best relates to outcome in acute intracerebral hemorrhage. We aimed to derive and validate a threshold for early postintracerebral hemorrhage change that best predicts 90-day outcomes. DESIGN: Derivation: retrospective analysis of collated clinical stroke trial data (Virtual International Stroke Trials Archive). VALIDATION: retrospective analysis of a prospective multicenter cohort study (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT]). SETTING: Neurocritical and ICUs. PATIENTS: Patients with acute intracerebral hemorrhage presenting less than 6 hours. Derivation: 552 patients; validation: 275 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We generated a receiver operating characteristic curve for the association between 24-hour National Institutes of Health Stroke Scale change and clinical outcome. The primary outcome was a modified Rankin Scale score of 4-6 at 90 days; secondary outcomes were other modified Rankin Scale score ranges (modified Rankin Scale, 2-6, 3-6, 5-6, 6). We employed Youden's J Index to select optimal cut points and calculated sensitivity, specificity, and predictive values. We determined independent predictors via multivariable logistic regression. The derived definitions were validated in the PREDICT cohort. Twenty-four-hour National Institutes of Health Stroke Scale change was strongly associated with 90-day outcome with an area under the receiver operating characteristic curve of 0.75. Youden's method showed an optimum cut point at -0.5, corresponding to National Institutes of Health Stroke Scale change of greater than or equal to 0 (a lack of clinical improvement), which was seen in 46%. Early neurologic change accurately predicted poor outcome when defined as greater than or equal to 0 (sensitivity, 65%; specificity, 73%; positive predictive value, 70%; adjusted odds ratio, 5.05 [CI, 3.25-7.85]) or greater than or equal to 4 (sensitivity, 19%; specificity, 98%; positive predictive value, 91%; adjusted odds ratio, 12.24 [CI, 4.08-36.66]). All definitions reproduced well in the validation cohort. CONCLUSIONS: Lack of clinical improvement at 24 hours robustly predicted poor outcome and showed good discrimination for individual patients who would do poorly. These findings are useful for prognostication and may also present as a potential early surrogate outcome for future intracerebral hemorrhage treatment trials.

Perihematomal Edema Is Greater in the Presence of a Spot Sign but Does Not Predict Intracerebral Hematoma Expansion.

BACKGROUND AND PURPOSE: Perihematomal edema volume may be related to intracerebral hemorrhage (ICH) volume at baseline and, consequently, with hematoma expansion. However, the relationship between perihematomal edema and hematoma expansion has not been well established. We aimed to investigate the relationship among baseline perihematomal edema, the computed tomographic angiography spot sign, hematoma expansion, and clinical outcome in patients with acute ICH. METHODS: Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) was a prospective observational cohort study of ICH patients presenting within 6 hours from onset. Patients underwent computed tomography and computed tomographic angiography scans at baseline and 24-hour computed tomography scan. A post hoc analysis of absolute perihematomal edema and relative perihematomal edema (absolute perihematomal edema divided by ICH) volumes was performed on baseline computed tomography scans (n=353). Primary outcome was significant hematoma expansion (>6 mL or >33%). Secondary outcomes were early neurological deterioration, 90-day mortality, and poor outcome. RESULTS: Absolute perihematomal edema volume was higher in spot sign patients (24.5 [11.5-41.8] versus 12.6 [6.9-22] mL; P<0.001), but it was strongly correlated with ICH volume (ρ=0.905; P<0.001). Patients who experienced significant hematoma expansion had higher absolute perihematomal edema volume (18.4 [10-34.6] versus 11.8 [6.5-22] mL; P<0.001) but similar relative perihematomal edema volume (1.09 [0.89-1.37] versus 1.12 [0.88-1.54]; P=0.400). Absolute perihematomal edema volume and poorer outcomes were higher by tertiles of ICH volume, and perihematomal edema volume did not independently predict significant hematoma expansion. CONCLUSIONS: Perihematomal edema volume is greater at baseline in the presence of a spot sign. However, it is strongly correlated with ICH volume and does not independently predict hematoma expansion.

Validation of the 9-Point and 24-Point Hematoma Expansion Prediction Scores and Derivation of the PREDICT A/B Scores.

BACKGROUND AND PURPOSE: Nine- and 24-point prediction scores have recently been published to predict hematoma expansion (HE) in acute intracerebral hemorrhage. We sought to validate these scores and perform an independent analysis of HE predictors. METHODS: We retrospectively studied 301 primary or anticoagulation-associated intracerebral hemorrhage patients presenting <6 hours post ictus prospectively enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus Computed Tomography (PREDICT) study. Patients underwent baseline computed tomography angiography and 24-hour noncontrast computed tomography follow-up for HE analysis. Discrimination and calibration of the 9- and 24-point scores was assessed. Independent predictors of HE were identified using multivariable regression and incorporated into the PREDICT A/B scores, which were then compared with existing scores. RESULTS: The 9- and 24-point HE scores demonstrated acceptable discrimination for HE>6 mL or 33% and >6 mL, respectively (area under the curve of 0.706 and 0.755, respectively). The 24-point score demonstrated appropriate calibration in the PREDICT cohort (χ2 statistic, 11.5; P=0.175), whereas the 9-point score demonstrated poor calibration (χ2 statistic, 34.3; P<0.001). Independent HE predictors included spot sign number, time from onset, warfarin use or international normalized ratio>1.5, Glasgow Coma Scale, and National Institutes of Health Stroke Scale and were included in PREDICT A/B scores. PREDICT A showed improved discrimination compared with both existing scores, whereas performance of PREDICT B varied by definition of expansion. CONCLUSIONS: The 9- and 24-point expansion scores demonstrate acceptable discrimination in an independent multicenter cohort; however, calibration was suboptimal for the 9-point score. The PREDICT A score showed improved discrimination for HE prediction but requires independent validation.

Intracerebral Hematoma Morphologic Appearance on Noncontrast Computed Tomography Predicts Significant Hematoma Expansion.

BACKGROUND AND PURPOSE: Hematoma expansion in intracerebral hemorrhage is associated with higher morbidity and mortality. The computed tomography (CT) angiographic spot sign is highly predictive of expansion, but other morphological features of intracerebral hemorrhage such as fluid levels, density heterogeneity, and margin irregularity may also predict expansion, particularly in centres where CT angiography is not readily available. METHODS: Baseline noncontrast CT scans from patients enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study were assessed for the presence of fluid levels and degree of density heterogeneity and margin irregularity using previously validated scales. Presence and grade of these metrics were correlated with the presence of hematoma expansion as defined by the PREDICT study on 24-hour follow-up scan. RESULTS: Three hundred eleven patients were included in the analysis. The presence of fluid levels and increasing heterogeneity and irregularity were associated with 24-hour hematoma expansion (P=0.021, 0.003 and 0.049, respectively) as well as increases in absolute hematoma size. Fluid levels had the highest positive predictive value (50%; 28%-71%), whereas margin irregularity had the highest negative predictive value (78%; 71%-85). Noncontrast metrics had comparable predictive values as spot sign for expansion when controlled for vitamin K, antiplatelet use, and baseline National Institutes of Health Stroke Scale, although in a combined area under the receiver-operating characteristic curve model, spot sign remained the most predictive. CONCLUSIONS: Fluid levels, density heterogeneity, and margin irregularity on noncontrast CT are associated with hematoma expansion at 24 hours. These markers may assist in prediction of outcomes in scenarios where CT angiography is not readily available and may be of future help in refining the predictive value of the CT angiography spot sign.

Venous phase of computed tomography angiography increases spot sign detection, but intracerebral hemorrhage expansion is greater in spot signs detected in arterial phase.

BACKGROUND AND PURPOSE: Variability in computed tomography angiography (CTA) acquisitions may be one explanation for the modest accuracy of the spot sign for predicting intracerebral hemorrhage expansion detected in the multicenter Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study. This study aimed to determine the frequency of the spot sign in intracerebral hemorrhage and its relationship with hematoma expansion depending on the phase of image acquisition. METHODS: PREDICT study was a prospective observational cohort study of patients with intracerebral hemorrhage presenting within 6 hours from onset. A post hoc analysis of the Hounsfield units of an artery and venous structure were measured on CTA source images of the entire PREDICT cohort in a core laboratory. Each CTA study was classified into arterial or venous phase and into 1 of 5 specific image acquisition phases. Significant hematoma expansion and total hematoma enlargement were recorded at 24 hours. RESULTS: Overall (n=371), 77.9% of CTA were acquired in arterial phase. The spot sign, present in 29.9% of patients, was more frequently seen in venous phase as compared with arterial phase (39% versus 27.3%; P=0.041) and the later the phase of image acquisition (P=0.095). Significant hematoma expansion (P=0.253) and higher total hematoma enlargement (P=0.019) were observed more frequently among spot sign-positive patients with earlier phases of image acquisition. CONCLUSIONS: Later image acquisition of CTA improves the frequency of spot sign detection. However, spot signs identified in earlier phases may be associated with greater absolute enlargement. A multiphase CTA including arterial and venous acquisitions could be optimal in patients with intracerebral hemorrhage.

Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial.

BACKGROUND: Carotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15-20% of acute stroke with large vessel occlusion. AIMS: We investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg) in patients with carotid TL. METHODS: This is a substudy of the alteplase compared with the tenecteplase trial. Patients with ⩾70% stenosis of the extracranial internal carotid artery (ICA) and concomitant occlusion of the intracranial ICA, M1 or M2 segments of the middle cerebral artery on baseline computed tomography angiography (CTA) were included. Primary outcome was 90-day-modified Rankin Scale (mRS) 0-1. Secondary outcomes were mRS 0-2, mortality, and symptomatic ICH (sICH). Angiographic outcomes were successful recanalization (revised Arterial Occlusive Lesion (rAOL) 2b-3) on first and successful reperfusion (eTICI 2b-3) on final angiographic acquisitions. Multivariable mixed-effects logistic regression was performed. RESULTS: Among 1577 alteplase versus tenecteplase randomized controlled trial (AcT) patients, 128 (18.8%) had carotid TL. Of these, 93 (72.7%) underwent intravenous thrombolysis plus endovascular thrombectomy (IVT + EVT), while 35 (27.3%) were treated with IVT alone. In the IVT + EVT group, tenecteplase was associated with higher odds of 90-day-mRS 0-1 (46.0% vs. 32.6%, adjusted OR (aOR) 3.21; 95% CI = 1.06-9.71) compared with alteplase. No statistically significant differences in rates of mRS 0-2 (aOR 1.53; 95% CI = 0.51-4.55), initial rAOL 2b-3 (16.3% vs. 28.6%), final eTICI 2b-3 (83.7% vs. 85.7%), and mortality (18.0% vs. 16.3%) were found. SICH only occurred in one patient. There were no differences in outcomes between thrombolytic agents in the IVT-only group. CONCLUSION: In patients with carotid TL treated with EVT, intravenous tenecteplase may be associated with similar or better clinical outcomes, similar angiographic reperfusion rates, and safety outcomes as compared with alteplase.

Spot sign number is the most important spot sign characteristic for predicting hematoma expansion using first-pass computed tomography angiography: analysis from the PREDICT study.

BACKGROUND AND PURPOSE: The spot sign score (SSS) provides risk stratification for hematoma expansion in acute intracerebral hemorrhage; however, external validation is needed. We sought to validate the SSS and assess prognostic performance of individual spot characteristics associated with hematoma expansion from a prospective multicenter intracerebral hemorrhage study. METHODS: Two hundred twenty-eight intracerebral hemorrhage patients within 6 hours after ictus were enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study, a multicenter prospective intracerebral hemorrhage cohort study. Patients were evaluated with baseline noncontrast computerized tomography, computerized tomography angiography, and 24-hour follow-up computerized tomography. Primary outcome was significant hematoma expansion (>6 mL or >33%) and secondary outcome was absolute and relative expansion. Blinded computerized tomography angiography spot sign characterization and SSS calculation were independently performed by 2 neuroradiologists and a radiology resident. Diagnostic performance of the SSS and individual spot characteristics were examined with multivariable regression, receiver operating characteristic analysis, and tests for trend. RESULTS: SSS and spot number independently predicted significant, absolute, and relative hematoma expansion (P<0.05 each) and demonstrated near perfect interobserver agreement (κ=0.82 and κ=0.85, respectively). Incremental risk of hematoma expansion among spot-positive patients was not identified for SSS (P trend=0.720) but was demonstrated for spot number (P trend=0.050). Spot number and SSS demonstrated similar area under the curve (0.69 versus 0.68; P=0.306) for hematoma expansion. CONCLUSIONS: Multicenter external validation of the SSS demonstrates that the spot number alone provides similar prediction but improved risk stratification of hematoma expansion compared with the SSS.