Background: It is unclear if revascularization therapies become less effective at recanalizing occlusions over time. We evaluated the association between time metrics and successful reperfusion in patients treated with thrombolysis for anterior circulation large vessel occlusion (LVO) strokes. Methods: We included LVO patients from the AcT (Alteplase compared to Tenecteplase) trial who underwent digital subtraction angiography. Logistic regression was performed to determine associations between time metrics and reperfusion outcomes: initial successful reperfusion (eTICI score ≥ 2b on first run), initial eTICI score, first pass effect (final eTICI 2b-3 after one thrombectomy pass), and final eTICI score. Models adjusted for age, sex, baseline NIHSS, occlusion location, treatment allocation and needle-to-groin time. Results: Among 471 patients, 46 (9.7%) achieved initial successful reperfusion (initial eTICI ≥2b) post-thrombolysis and prior to thrombectomy. Median age was 73 years, 50.7% were female; M1 occlusions were most common (40.6%). Onset-to-needle (median 110 vs 105 min; p = 0.055), onset-to-groin (157 vs 155 min; p = 0.376), and needle-to-groin times (46 vs 39 min; p = 0.394) did not differ between patients with vs without initial successful reperfusion. Onset-to-needle time was not associated with initial successful reperfusion (aOR 1.00 per 10-min increase; 95% CI 0.96–1.05). Onset-to-groin time was also not associated with first-pass effect (aOR 0.99; 95% CI 0.97–1.02) or final eTICI (aOR 1.00; 95% CI 0.98–1.02). Conclusion: Time from symptom onset was not significantly associated with angiographic reperfusion outcomes among patients with anterior circulation LVO stroke treated within the 4.5 h window. Further studies should explore this relationship across wider time windows, stroke subtypes, and treatments.

Brain frailty measures like atrophy and white matter changes (WMC) are becoming increasingly relevant in stroke outcome prediction but are conventionally thought to be best seen on MRI compared to CT. We assessed agreement between baseline CT vs follow-up MRI ratings for brain atrophy and WMC; and compared their discriminative ability for 90-day functional outcomes in acute ischemic stroke. In this post-hoc, observational analysis of baseline CT and follow-up MRI data from the Alteplase compared to Tenecteplase (AcT) randomised-controlled trial, experts assessed brain atrophy, periventricular and deep WMC using established visual-rating scales. Binary agreement (none-mild vs. moderate-severe) and agreement across the full scores between atrophy and WMC measures on CT and MRI were calculated using Gwet’s agreement coefficient (AC1). Logistic regression estimated discrimination for 90-day modified Rankin Scale (mRS) 0–1. Agreement of AUCs for CT and MRI models were compared using DeLong’s test. Among 1577 AcT participants, 491(31.1

Stroke has become the single leading neurological illness that results in neurological disability and is the second most common cause of death worldwide. Approximately 85% of strokes are ischemic, whereas the remaining 15% are hemorrhagic. With the advent of increasingly effective treatment modalities, such as intravenous thrombolytics and endovascular mechanical thrombectomy, there has been a growing disparity in the ability to provide standard of care, despite substantial efforts made in lower- and middle-income countries. substantial effort in high-income countries to provide the current standard of care to patients with stroke, with the hope of improving outcomes. Extensive research has shown that the disparities in treatment among various countries stem from multiple sociocultural barriers and the lack of robust healthcare infrastructure. The societal influences in play include the lack of knowledge of stroke symptoms, cultural beliefs, health, and spiritual fatalism, which are then associated with delayed healthcare-seeking behaviors. As a result, it is imperative to increase access to treatment for patients with stroke to address inequities in stroke care and diminish the global burden of stroke. This narrative review highlights causes of major gaps in stroke treatment infrastructure in several global communities and examines the pertinent sociocultural factors that impede progress in stroke treatment.

Abstract Background and aims Cortical venous opacification may reflect ischemic severity in large vessel occlusion (LVO) strokes, but its association with outcomes in tandem occlusion (cervical ICA occlusion with concurrent intracranial ICA, M1, or M2 occlusion) is unclear. Methods We performed a post-hoc analysis of the alteplase compared to tenecteplase (AcT) trial. The sphenoparietal sinus, superficial middle cerebral vein, and vein of Labbé received a Cortical Venous Opacification Score (COVES) graded 0-2 on CTA (total 0–6: lower scores indicate poorer filling). COVES+ with the internal cerebral vein (total 0-8) was also assessed. Associations with functional and safety outcomes were evaluated using regression models adjusted for age, NIHSS, ASPECTS, and door-to-needle time. Results Among 127 patients with tandem occlusion (median age 69 [IQR 60–78] years; 32% female), 17 (13.4%) had a COVES of 0 and 110 (86.6%) had COVES >0. Compared to COVES >0, patients with COVES 0 had higher NIHSS (median 20 [IQR 18–22] vs 16 [IQR 10–20], p=0.002), lower ASPECTS (median 8 [range 4–10] vs 8 [range 5–10], p=0.031), and a higher proportion with poor collaterals (29.4% vs 8.2%). COVES score was not associated with 90-day functional outcomes (ordinal mRS: acOR 1.04 [95% CI 0.86-1.26]), mortality, or symptomatic intracranial hemorrhage. COVES+ also showed no associations with outcomes. Conclusions Cortical venous opacification was not associated with functional or safety outcomes in patients with tandem occlusion in the AcT trial. These findings may reflect the small sample size or differences from the broader LVO population, warranting further study. Conflict of interest CreeAnn Phillips: nothing to disclose, Nahal Farhani: nothing to disclose, Alexandre Poppe: nothing to disclose, Bijoy Menon:nothing to disclose, Nishita Singh: nothing to disclose, Fouzi Bala: nothing to disclose, Taha Aslan: nothing to disclose, Mohammed Almekhlafi: nothing to disclose, Katrina Ignacio: nothing to disclose.

Background: Symptomatic nonstenotic carotid disease is an increasingly recognized etiology in ischemic stroke, particularlyin the presenceofcertain high-risk plaquefeatures.The aim ofthis population-level clinical imaging studywas to examine the risk of ipsilateral and recurrent stroke in symptomatic nonstenotic carotid disease with 5-year follow-up. Methods: All patients with an index stroke/transient ischemic attack in calendar year 2019 were identified, and baseline and follow-up imaging were analyzed through December 2023 to assess recurrent stroke. Computed tomography angiograms were assessed for plaque features such as degree of stenosis, plaque thickness, calcification, plaque irregularity, ulceration, positive rim sign, and focal vessel caliber increase. Parenchymal imaging was assessed for infarct presence on same side as carotid disease (concordant stroke). Analysis was performed at the patient and carotid level using unadjusted and adjusted logistic regression analysis. Sensitivity analysis excluding patients with competing stroke etiologies was also completed. Results: Of the total 1249 patients with stroke, 658 patients with available neck imaging and <= 50% stenosis were included. Of these, 153 (23.5%) had concordant stroke, and 76 (11.6%) had recurrent stroke. In adjusted analysis, there was significantly increased odds of concordant stroke at index presentation with stenosis grade (adjusted odds ratio [aOR], 3.56; 95% confidence interval [CI], 2.99-4.25) and plaque thickness (aOR, 1.19; 95% CI, 1.03-1.38). Similarly, adjusted analysis showed significant increase in odds of recurrent concordant stroke with degree of stenosis (aOR, 2.39; 95% CI, 1.94-2.95), plaque thickness (aOR, 1.32; 95% CI, 1.05-1.67), and plaque ulceration (aOR, 3.86; 95% CI, 1.31-11.35). Results remained consistent after sensitivity analysis. Conclusions: This retrospective analysis of the population-level clinical imaging study shows that plaque thickness, degree of stenosis, and plaque ulceration are associated with increased risk of index and recurrent ischemic strokes. More prospective data is needed to validate these findings. (JVS-Vascular Insights 2026;4:100461.)

Introduction: Cerebral amyloid angiopathy (CAA) is thought to increase the risk of post thrombolytic intracranial bleeding, yet CAA neuroimaging markers and MRI criteria have not been systematically evaluated in large acute stroke trials. We therefore examined the association of various iterations of the Boston CAA criteria and their constituent markers with hemorrhagic risks and functional outcomes after intravenous thrombolysis in the Alteplase compared to Tenecteplase (AcT) trial. Methods: This post-hoc study included AcT participants who underwent follow-up brain MRI (n = 482). Blinded raters recorded lobar cerebral microbleeds (CMBs), cortical superficial siderosis (CSS), white-matter-hyperintensity (WMH) multispot sign, and centrum-semiovale enlarged perivascular spaces, and classified “possible” and “probable” CAA according to radiological Boston criteria iterations 1.0, 1.5, and 2.0. Multivariable logistic or ordinal regressions, adjusted for age, sex, baseline NIHSS, onset-to-needle time, thrombolytic agent, diabetes mellitus, hypertension, and endovascular therapy assessed associations with primary safety endpoints: 90-day mortality, symptomatic intracerebra l hemorrhage, any ICH, and Heidelberg hemorrhage grade, and secondary functional endpoints (modified Rankin Scale [mRS] 0–1 and ordinal mRS shift). Results: CSS emerged as the dominant harmful marker: each increment independently increased 90-day mortality (adjusted odds ratio [aOR] 1.42, 95%CI1.18–1.71), heightened the risk of sICH (aOR 3.88, 2.87–5.26) and any intracranial hemorrhage (aOR 1.91, 1.22–2.98), worsened hemorrhage severity on the Heidelberg scale, reduced the likelihood of excellent functional recovery (aOR 0.70, 0.64–0.77) and shifted the entire mRS distribution toward greater disability (adjusted common OR 1.74, 1.58–1.91). Boston 1.0 and 1.5 “probable”criteria increased the odds of any intracranial hemorrhage (aOR 2.57 and 2.39), whereas Boston 1.5 “possible” criteria were associated with worsened disability (acOR 2.34, 1.30–4.22). Conclusions: In thrombolyzed patients with acute ischemic stroke, CSS burden is strongly and consistently associated with higher risk of severe hemorrhage, disability and death, making it the most actionable CAA marker when weighing thrombolytic risk. Meeting Boston 1.0 or 1.5 “probable” radiologic criteria, increases hemorrhagic risk, but meeting the latest 2.0 criteria does not.

Abstract Background and aims Current treatment of symptomatic carotid stenosis relies on data that are more than 30 years old. There is limited reliable information on the stroke rate with modern, intensive medical therapy (IMT). The aim of this pragmatic registry was to provide an estimate of the ipsilateral stroke rate for patients with 50-99% symptomatic carotid stenosis who have at least one feature suggesting reduced stroke risk. Methods IMT was provided to all participants. IMT consists of dual antiplatelet therapy (short-term), high potency statins, blood pressure control, and lifestyle modification with risk factor education. Criteria for enrollment include any one of three clinical or radiologic markers. Clinical 1) Women 2) Retinal ischemic event only 3) Last symptomatic event >1 week ago. Radiologic: 1) TCD negative for emboli 2) MRI negative for intraplaque hemorrhage 3) High risk TIA with negative DWI. The primary endpoint is ipsilateral ischemic stroke within 12 months of enrollment. Results The registry completed enrollment in Sept 2025 with 114 patients (53% women), recruited from 18 centers in N America. 70% of patients qualified with stroke, 30% with TIA. All patients completed 6 month follow-up, with the ipsilateral stroke rate being 4.4%. Eight patients have died (7%). Information on stroke severity will be presented. Conclusions SCORE Registry data will allow clinicians to refine carotid stenosis decision making in symptomatic patients with >50% stenosis and potentially justify a future phase III RCT. With 6 months of follow-up in all patients, the stroke rate appears reduced compared to historical controls. Conflict of interest

BACKGROUND:Cerebral amyloid angiopathy (CAA) is thought to increase the risk of postthrombolytic intracranial bleeding, yet CAA neuroimaging markers and magnetic resonance imaging criteria have not been systematically evaluated in large acute stroke trials. We, therefore, examined the association of radiological Boston CAA criteria and their constituent markers with hemorrhagic risks and functional outcomes after intravenous thrombolysis in the AcT trial (Alteplase Compared to Tenecteplase). METHODS:Blinded raters recorded lobar cerebral microbleeds, cortical superficial siderosis, white matter hyperintensity multispot sign, and centrum semiovale enlarged perivascular spaces, and classified possible and probable CAA according to radiological Boston criteria iterations, versions 1.0, 1.5, and 2.0. Multivariable logistic or ordinal regressions, adjusted for age, sex, baseline stroke severity, diabetes, hypertension, onset-to-needle time, thrombolytic agent, and endovascular therapy, assessed associations of these features/criteria with safety end points: symptomatic intracerebral hemorrhage (ICH), any ICH, Heidelberg hemorrhage grade, 90-day mortality, and functional outcomes (modified Rankin Scale score of 0-1 and ordinal modified Rankin Scale score shift). RESULTS:Among 1600 patients in the trial, 482 had suitable magnetic resonance imaging (mean age, 71 years; 47.1% female). Cortical superficial siderosis burden emerged as the dominant harmful marker: each increment was associated with increased risk of symptomatic ICH (adjusted odds ratio [aOR] per additional affected sulcus, 3.88 [95% CI, 2.87-5.26]), any ICH (aOR, 1.91 [95% CI, 1.22-2.98]), hemorrhage severity, 90-day mortality (aOR, 1.42 [95% CI, 1.18-1.71]), worse modified Rankin Scale scores (adjusted common odds ratio, 1.74 [95% CI, 1.58-1.91]), and lower odds of excellent functional recovery (aOR, 0.70 [95% CI, 0.64-0.77]). Fulfilling probable radiological Boston criteria, versions 1.0 and 1.5, increased odds of any ICH (aOR, 2.57 and 2.39 [95% CI, 2.05-3.23]; aOR, 2.39 [95% CI, 1.71-3.34], respectively), whereas fulfilling possible Boston criteria, version 1.5, was associated with worse modified Rankin Scale scores (adjusted common odds ratio, 2.34 [95% CI, 1.30-4.22]). Boston criteria, version 2.0, were not significantly associated with any hemorrhagic outcomes. CONCLUSIONS:In thrombolyzed patients with acute ischemic stroke, cortical superficial siderosis burden is strongly and consistently associated with higher risk of severe hemorrhage, disability, and death, making it a particularly relevant CAA marker when weighing thrombolytic risk versus benefit. Meeting radiological Boston criteria, versions 1.0 or 1.5, increases hemorrhagic risk, but meeting the latest 2.0 criteria does not.

BACKGROUND:To determine whether computed tomography (CT) thrombus characteristics modify the effect of intravenous (IV) thrombolysis type (tenecteplase vs alteplase) on outcomes. METHODS:This is a secondary analysis of the Alteplase compared to Tenecteplase (AcT) trial. Patients with visible intracranial occlusions on thin-slice baseline imaging were included. Key thrombus characteristics assessed by CT imaging were hyperdense artery sign, thrombus length, residual flow, clot burden score, and occlusion site. Multivariable analyses were performed to test for interactions between thrombolysis type and thrombus characteristics on clinical and angiographic outcomes. RESULTS:Of 1577 patients, 939 met inclusion criteria; 479 (51.0%) received tenecteplase and 460 (49.0%) alteplase. Among the 498 patients (53.0%) treated with endovascular thrombectomy (EVT), angiographic outcomes were comparable between treatment groups. A significant interaction was observed between thrombolysis type and thrombus length; longer thrombi were associated with reduced likelihood of modified Rankin Scale (mRS) 0-1 with alteplase (adjusted odds ratio (aOR) per 1 mm increase, 0.97 (95% confidence interval (CI): 0.95-1.00)), but not with tenecteplase (aOR: 1.00 (95% CI: 0.98-1.02); interaction p = 0.04). Similarly, the presence of residual flow within the thrombus was associated with higher odds of mRS 0-2 in the alteplase group (aOR: 2.00 (95% CI: 1.25-3.20)), but had no significant effect in the tenecteplase group (aOR: 0.93 (95% CI: 0.62-1.41); interaction p = 0.01). No other significant interactions between thrombus characteristics and thrombolysis type were identified. CONCLUSION:In the AcT trial, alteplase appeared less effective with longer thrombi and those lacking residual flow, whereas IV tenecteplase showed more consistent effectiveness across thrombus characteristics. These findings require confirmation in future prospective studies.

BACKGROUND:Data are scarce regarding the frequency, characteristics, and associated recurrent event risks of cerebrovascular fibromuscular dysplasia (cFMD) in patients presenting with ischemic stroke and transient ischemic attack (TIA). METHODS:We included patients diagnosed with ischemic stroke/TIA in an entire Canadian province (Alberta) from 1-April-2016 to 31-March-2017, with follow-up of at least 5-years until 31-March-2022. Direct neuroimaging review and keyword searches of radiologist reports were used to identify suspected cFMD cases. Clinical and imaging characteristics and event etiology were ascertained. 5-year hazards of recurrent stroke/TIA were estimated, adjusted for age, sex, and vascular risk factors. RESULTS:Among 4,033 patients with ischemic stroke/TIA who underwent CT/MR angiography, we found 35 (0.86%) cases of cFMD. Patients with cFMD had similar age (median:74[IQR:53-88] vs 69[IQR:20-99] years, p = 0.09) and higher female preponderance (80% vs 44.9%, p < 0.0001) versus those without. The extracranial proximal internal carotid artery (ICA) was most frequently involved. Most observed infarcts (23/26, 88.5%) occurred downstream from carotid/vertebral arteries with cFMD changes. Strokes/TIAs for most cFMD patients (27/35, 77.1%) were adjudicated to be of otherwise undetermined etiology following conventional investigations. All-cause mortality occurred in 10 (28.5%) and recurrent stroke/TIA in 8 (22.9%) patients at 5-years; this was not significantly higher than patients without FMD (aHR: 1.54, 95%CI:0.77-3.11). CONCLUSIONS:cFMD was a rare finding in this subset of patients with stroke/TIA who underwent adequate neuroimaging, primarily affecting females and the extracranial proximal ICA. Infarcts in these patients often occurred in the territory of FMD-affected vessels and events were often classified as cryptogenic. Whereas these patients had substantial rates of recurrent stroke/TIA and mortality, the adjusted hazards versus patients without cFMD were imprecise.

OBJECTIVE:Launched in August 2024, the ACT-GLOBAL (a multifactorial, multiarm, multistage, randomized, global adaptive platform) trial is the first multinational adaptive platform trial for acute stroke. Because it proposes to enroll participants by deferral of consent, the ACT-GLOBAL trial seeks to publish an explicit justification for this practice. METHODS:Following a standardized protocol for establishing whether it is justified to use deferral of consent, all active domains of the ACT-GLOBAL platform adaptive trial were considered according to six questions: (1) Is there evidence-based uncertainty about the research question?; (2) is the standard of care treatment included in the trial, meaning that patients are unlikely to be disadvantaged by their participation?; (3) is the trial of sufficient methodological rigor that it can result in a change of practice?; (4) Are patients eligible for enrollment in the trial likely to be incapable of providing their own consent?; (5) Will seeking to obtain consent from a surrogate decision-maker meaningfully delay treatment and impact outcomes?; and (6) Are steps taken to mitigate the compromise to individual autonomy? RESULTS:The leadership of the ACT-GLOBAL trial is able to answer affirmatively the six questions outlined above in relation to each of the trial's current domains. The results of this analysis suggest that the use of deferral of consent in the ACT-GLOBAL trial is ethically justified, where permitted by law. CONCLUSION:This exercise demonstrates the utility of following an accepted protocol for determining whether alterations to standard consent practices such as deferral of consent are ethically justified in acute stroke research.

BACKGROUND:Complete recanalization of cerebral arteries is strongly associated with good functional outcome in ischemic stroke. We hypothesize that successful recanalization results in better functional outcomes. METHODS:This is a secondary observational cohort analysis of TEMPO-2 (Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion), a randomized controlled trial comparing tenecteplase with standard of care (control) in minor stroke (National Institutes of Health Stroke Scale score ≤5) with intracranial occlusion/focal perfusion abnormality ≤12 hours of onset. Among those enrolled based on computed tomography angiography with visible occlusion, a follow-up computed tomography angiography was done at 4 to 8 hours after randomization. The primary outcome was return to baseline functional outcomes using the modified Rankin Scale score at 90 days. Safety outcomes included stroke progression (National Institutes of Health Stroke Scale score ≥2 worsening), bleeding events, and mortality. Patients with successful recanalization, defined as revised Arterial Occlusive Lesion score ≥2b/3, were compared with those with unsuccessful recanalization on follow-up computed tomography angiography. Regression analysis was used to assess the association of successful recanalization with outcomes after adjusting for age, sex, baseline stroke severity, and onset-to-randomization time. RESULTS:Of the 886 enrolled patients, 517 (58.3%) with follow-up computed tomography angiography were included. Of these, 178 (34.6%) had successful recanalization (122 [68.5%]: tenecteplase, 56 (31.5%): control), and 336 (65.4%) did not achieve successful recanalization (unsuccessful recanalization; 134: tenecteplase, 202: control). Baseline characteristics were similar between patients with and without successful recanalization. Successful recanalization was significantly associated with the primary outcome as compared with unsuccessful recanalization (adjusted risk ratio, 1.21 [95% CI, 1.07-1.34]). Patients with successful recanalization had significantly lower rates of stroke progression as compared with unsuccessful recanalization (2.8% versus 13.1%, adjusted risk ratio, 0.21 [95% CI, 0.08-0.52]). Multivariable analysis showed that tenecteplase treatment was the strongest independent predictor of successful recanalization (odds ratio, 3.48 [95% CI, 2.33-5.18]). CONCLUSIONS:Successful recanalization is a critical determinant of early and 90-day functional recovery in patients with minor stroke with intracranial occlusion, regardless of treatment modality. Tenecteplase significantly increases the odds of achieving successful recanalization compared with standard care. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02398656.

Intravenous thrombolysis for ischemic stroke after recent direct oral anticoagulant (DOAC) ingestion remains controversial due to hemorrhagic risk, limited rapid testing and inconsistent reversal strategies. We conducted an invite-only, web-based cross-sectional survey of Canadian stroke centers using a structured questionnaire. DOAC level testing was inconsistently available, with 9/13 centers (69%) reporting access but 8/13 centers (61%) reporting turnaround times exceeding 30 minutes. Consequently, 9/13 centers (69%) did not routinely use DOAC levels to guide thrombolysis decisions. Current practice demonstrates substantial variability and uncertainty, highlighting important evidence gaps and the potential role of clinical trials and consensus guideline development.

BACKGROUND:Intracranial hemorrhage (ICH) negatively impacts functional outcomes after ischemic stroke, with potentially disproportionate impacts in patients with minor stroke. This study aimed to evaluate the effect of ICH on outcomes in minor ischemic stroke and to identify predictors associated with ICH. METHODS:This was a secondary analysis of the TEMPO-2 (A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) multicenter, randomized trial, which compared tenecteplase with nonthrombolytic standard care in patients within 12 hours of symptom onset with minor stroke (National Institutes of Health Stroke Scale score ≤5) and a visible vessel occlusion or perfusion mismatch. Follow-up imaging was assessed for hemorrhage using the Heidelberg classification. Symptomatic ICH was defined as any hemorrhage associated with neurological deterioration. The primary outcome was return to premorbid functional status at 90 days, measured using the modified Rankin Scale. Mixed-effects regression was used to assess the effect of ICH status on outcomes, adjusting for treatment, age, sex, baseline stroke severity, and onset-to-randomization time, with region included as a random effect. RESULTS:Among 884 participants, 865 had complete 24-hour imaging and follow-up. Using complete case analysis (n=865), any ICH occurred in 102 participants (11.8%). Patients with any ICH (median age, 70 years; 35.3% females) more frequently had premorbid hypertension (71.6% versus 57.7%) and atrial fibrillation (28.4% versus 18.1%). Any ICH was not associated with reduced odds of returning to baseline neurological function (adjusted odds ratio, 0.93 [95% CI, 0.87-1.00]) but was associated with higher 90-day mortality (9.8% versus 1.8%; adjusted hazard ratio, 3.71 [95% CI, 1.54-8.95]). Rates of any ICH were higher in tenecteplase than standard care (14.4% versus 9.2%; P=0.02), although most were petechial hemorrhagic transformations. Symptomatic ICH rates, although numerically higher, were not significantly different between the tenecteplase versus control arms (8 [1.9%] versus 2 [0.5%]; P=0.06). CONCLUSIONS:Although most hemorrhages were minor, the presence of any ICH was strongly associated with increased mortality, highlighting that even minor hemorrhagic transformation may be prognostically significant in patients with minor ischemic stroke.

BACKGROUND:Symptomatic nonstenotic (<50% stenosis) carotid disease in the presence of high-risk plaque features is a potential cause of ischemic stroke. We assessed stroke risk associated with symptomatic nonstenotic carotid disease. METHODS:This cross-sectional secondary analysis of the AcT (Alteplase Compared to Tenecteplase) randomized controlled trial evaluated baseline computed tomography angiograms for degree of internal carotid artery stenosis, plaque features and the presence of intraluminal thrombi, webs, dissection, and rim sign. Stroke location was evaluated on 24-hour follow-up imaging. At a carotid level, mixed-effects logistic regression models adjusted for age and sex, with patient identity as a random effect, examined associations between "concordant stroke" (ipsilateral acute stroke in the internal carotid artery territory) and symptomatic nonstenotic carotid disease. RESULTS:Of 1577 patients enrolled, 1407 (89.2%) with interpretable imaging were included: 329 (23.4%) had no carotid disease, 869 (61.8%) had nonstenotic carotid disease, and 209 (14.9%) had stenotic (≥50%) carotid disease in either the left or right internal carotid artery. Median age was 73 years (interquartile range, 63-83), with 48% female patients. Among 2519 (89.5%) internal carotid arteries with nonstenotic disease, 689 (27.4%) concordant strokes were identified. Intraluminal thrombi, carotid webs, carotid dissections, and carotid rim sign were significantly associated with concordant stroke (adjusted odds ratio, 8.11 [95% CI, 1.60-41.08]; adjusted odds ratio, 3.58 [95% CI, 1.53-8.35]; adjusted odds ratio, 6.77 [95% CI, 1.72-26.75]; and adjusted odds ratio, 3.17 [95% CI, 1.39-7.23], respectively). Results remained unchanged after excluding patients with atrial fibrillation and lacunar infarctions. CONCLUSIONS:Features other than the degree of stenosis should be considered when evaluating patients with carotid disease.

BACKGROUND:With the increasing use of tenecteplase, it is important to understand its safety compared with alteplase. We aimed to determine the incidence, predictors, and functional impact of serious adverse events (SAEs) in patients treated with alteplase versus tenecteplase. METHODS:This is a post hoc analysis of the AcT (Alteplase Compared to Tenecteplase) trial, a phase 3 multicenter randomized controlled trial that randomized 1577 ischemic patients with stroke (2019-2022) into tenecteplase versus alteplase presenting <4.5 hours of onset. SAEs were recorded within 24 hours of treatment and classified by organ system using the Medical Dictionary for Regulatory Activities. Mixed-effects logistic regression evaluated predictors of SAEs and their impact on 90-day modified Rankin Scale. RESULTS:Of the 1577 enrolled, 219 (13.9%) patients had SAEs. Patients with SAEs had higher National Institutes of Health Stroke Scale (median, 11 versus 9; P=0.002) and higher endovascular treatment rates (50.2% versus 29.2%; P<0.001) than those without SAEs. Nervous system disorders were the most common SAE (58.2%), including stroke worsening (26.7%) and intracranial hemorrhage (25%). No significant differences were observed in SAE distribution by thrombolytic. Patients with SAEs had higher 90-day modified Rankin Scale scores (median, 4 versus 2; odds ratio [OR], 3.93 [95% CI, 2.78-5.56]). Independent predictors of SAEs included baseline National Institutes of Health Stroke Scale (per SD increase: OR, 1.2 [95% CI, 1.0-1.5]), large-vessel occlusion (OR, 1.6 [95% CI, 1.1-2.5]), Alberta Stroke Program Early Computed Tomography Score (per point increase: OR, 0.9 [95% CI, 0.8-1.0]), and cerebral atrophy (per point increase: OR, 1.5 [95% CI, 1.1-1.9]). CONCLUSIONS:Our study found no difference between rate or type of SAEs by thrombolytic type, supporting the safety of tenecteplase. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03889249.