Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.

BACKGROUND: The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. METHODS: We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. RESULTS: Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. CONCLUSIONS: In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).

Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized Controlled ELAN Trial.

BACKGROUND: Whether hemorrhagic transformation (HT) modifies the treatment effect of early compared with late initiation of direct oral anticoagulation in people with ischemic stroke and atrial fibrillation is unknown. METHODS: This is a post hoc analysis of the ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation). The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on prerandomization imaging (core laboratory rating) using adjusted risk differences between treatment arms. RESULTS: Overall, 247 of 1970 participants (12.5%) had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated adjusted risk difference (early versus late) was -2.2% (95% CI, -7.8% to 3.5%) in people with HT (HI: -4.7% [95% CI, -10.8% to 1.4%]; PH: 6.1% [95% CI, -8.5% to 20.6%]) and -0.9% (95% CI, -2.6% to 0.8%) in people without HT. Numbers of symptomatic intracranial hemorrhage were identical in people with and without HT. With early treatment, the estimated adjusted risk difference for poor 90-day functional outcome (modified Rankin Scale score, 3-6) was 11.5% (95% CI, -0.8% to 23.8%) in participants with HT (HI: 7.4% [95% CI, -6.4% to 21.2%]; PH: 25.1% [95% CI, 0.2% to 50.0%]) and -2.6% (95% CI, -7.1% to 1.8%) in people without HT. CONCLUSIONS: We found no evidence of major treatment effect heterogeneity or safety concerns with early compared with late direct oral anticoagulation initiation in people with and without HT. However, early direct oral anticoagulation initiation may worsen functional outcomes in people with PH. REGISTRATION: URL: http://www.clinicaltrials.gov; Unique identifier: NCT03148457.

Toward Individual Treatment in Cervical Artery Dissection: Subgroup Analysis of the TREAT-CAD Randomized Trial.

OBJECTIVE: Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment. METHODS: This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing. RESULTS: All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation. INTERPRETATION: Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886-897.

Effect of Asymptomatic and Symptomatic COVID-19 on Acute Ischemic Stroke Revascularization Outcomes.

BACKGROUND: The association of COVID-19 with higher bleeding risk and worse outcomes in acute ischemic stroke (AIS) undergoing revascularization may be related to the presence of infection symptoms. We aimed to assess the safety and outcomes of revascularization treatments in patients with AIS with asymptomatic COVID-19 (AS-COVID) or symptomatic COVID-19 (S-COVID). METHODS: We conducted an international multicenter retrospective cohort study of consecutive AIS tested for SARS-CoV-2, receiving intravenous thrombolysis and endovascular treatment between 2020 and 2021. We compared COVID-negative controls, AS-COVID, and S-COVID using multivariable regression. We assessed symptomatic intracranial hemorrhage (symptomatic intracerebral hemorrhage), mortality, and 3-month disability (modified Rankin Scale score). RESULTS: Among 15 124 patients from 105 centers (median age, 71 years; 49% men; 39% treated with intravenous thrombolysis only; and 61% with endovascular treatment±intravenous thrombolysis), 849 (5.6%) had COVID-19, of whom 395 (46%) were asymptomatic and 454 (54%) symptomatic. Compared with controls, both patients with AS-COVID and S-COVID had higher symptomatic intracerebral hemorrhage rates (COVID-controls, 5%; AS-COVID, 7.6%; S-COVID, 9.4%; adjusted odds ratio [aOR], 1.43 [95% CI, 1.03-1.99]; aOR, 1.63 [95% CI, 1.14-2.32], respectively). Only in patients with symptomatic infections, we observed a significant increase in mortality at 24 hours (COVID-controls, 1.3%; S-COVID, 4.8%; aOR, 2.97 [95% CI, 1.76-5.03]) and 3 months (COVID-controls, 19.5%; S-COVID, 40%; aOR, 2.64 [95% CI, 2.06-3.37]). Patients with COVID-19 had worse 3-month disability regardless of disease symptoms although disability was affected to a greater extent in symptomatic patients (aOR for worse modified Rankin Scale score shift: AS-COVID, 1.25 [95% CI, 1.03-1.51]; S-COVID, 2.10 [95% CI, 1.75-2.53]). S-COVID had lower successful recanalization (74.9% versus 85.6%; P<0.001), first pass recanalization (20.3% versus 28.3%; P=0.005), and a higher number of passes. CONCLUSIONS: In AIS undergoing revascularization treatments, both AS-COVID and S-COVID influence the risk of intracranial bleeding and worse clinical outcomes. The magnitude of this effect is more pronounced in symptomatic infections, which also present less favorable recanalization outcomes. These findings emphasize the impact of SARS-CoV-2 infection on the prognosis of revascularized AIS independent of symptom status. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04895462.

Moving From CT to MRI Paradigm in Acute Ischemic Stroke: Feasibility, Effects on Stroke Diagnosis and Long-Term Outcomes.

BACKGROUND: The relative value of computed tomography (CT) and magnetic resonance imaging (MRI) in acute ischemic stroke (AIS) is debated. In May 2018, our center transitioned from using CT to MRI as first-line imaging for AIS. This retrospective study aims to assess the effects of this paradigm change on diagnosis and disability outcomes. METHODS: We compared all consecutive patients with confirmed diagnosis of AIS admitted to our center during the MRI-period (May 2018-August 2022) and an identical number of patients from the preceding CT-period (December 2012-April 2018). Univariable and multivariable analyses were performed to evaluate outcomes, including the number and delay of imaging exams, the rate of missed strokes, stroke mimics treated with thrombolysis, undetermined stroke mechanisms, length of hospitalization, and 3-month disability. RESULTS: The median age of the 2972 included patients was 76 years (interquartile range, 65-84), and 46% were female. In the MRI-period, 80% underwent MRI as first acute imaging. The proportion of patients requiring a second acute imaging modality for diagnostic ± revascularization reasons increased from 2.1% to 5% (Punadj <0.05), but it decreased in the subacute phase from 79.0% to 60.1% (Padj <0.05). In thrombolysis candidates, there was a 2-minute increase in door-to-imaging delay (Padj <0.05). The rates of initially missed AIS diagnosis was similar (3.8% versus 4.4%, Padj=0.32) and thrombolysis in stroke mimics decreased by half (8.6% versus 4.3%; Padj <0.05). Rates of unidentified stroke mechanism at hospital discharge were similar (22.8% versus 28.1%; Padj=0.99). The length of hospitalization decreased from 9 (interquartile range, 6-14) to 7 (interquartile range, 4-12) days (Padj=0.62). Disability at 3 months was similar (common adjusted odds ratio for favorable Rankin shift, 0.98 [95% CI, 0.71-1.36]; Padj=0.91), as well as mortality and symptomatic intracranial hemorrhage. CONCLUSIONS: A paradigm shift from CT to MRI as first-line imaging for AIS seems feasible in a comprehensive stroke center, with a minimally increased delay to imaging in thrombolysis candidates. MRI was associated with reduced thrombolysis rates of stroke mimics and subacute neuroimaging needs.

Endovascular Versus Medical Therapy in Posterior Cerebral Artery Stroke: Role of Baseline NIHSS Score and Occlusion Site.

BACKGROUND: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site. METHODS: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0-1), functional independence (mRS score 0-2), symptomatic intracranial hemorrhage, and mortality. RESULTS: From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution (Pinteraction=0.312) but did with functional independence (Pinteraction=0.010), with a similar trend on excellent outcome (Pinteraction=0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score >6 (mRS score 0-1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22-3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08-2.51]) but not in those with NIHSS score ≤6 (mRS score 0-1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49-1.64]; mRS score 0-2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30-1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score (Pinteraction=0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 (Pinteraction=0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11-20.28]; NIHSS score >6: aOR, 1.98 [95% CI, 1.08-3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM. CONCLUSIONS: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score >6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage.

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Sex Differences in Outcomes of Late-Window Endovascular Stroke Therapy.

BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONS: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.

Revascularization of arterial occlusions in posterior circulation acute ischemic stroke.

PURPOSE OF REVIEW: This review highlights the latest advancements achieved in the revascularization of arterial occlusions associated with an acute ischemic stroke affecting the posterior circulation. It delves into the frequency and outcomes based on specific arterial segments and presents current evidence supporting revascularization treatments, including intravenous thrombolysis and endovascular thrombectomy. RECENT FINDINGS: Comprehensive evidence for treatment across major arterial segments of the posterior circulation -- vertebral artery, basilar artery, posterior cerebral artery, cerebellar arteries, and multilevel posterior occlusions -- is provided. Additionally, the latest findings from randomized clinical trials on basilar artery occlusion are explored alongside results from extensive retrospective analyses of isolated vertebral and posterior cerebral artery occlusions. SUMMARY: Current research supports the treatment decision in acute ischemic strokes of the posterior circulation using both intravenous thrombolysis and endovascular thrombectomy. This review also emphasizes existing knowledge gaps in the management of these strokes and advocates for more randomized clinical trials, notably concerning the posterior cerebral artery (currently ongoing), isolated vertebral artery, and multilevel posterior circulation occlusions.

Endovascular Therapy for Stroke Due to Basilar-Artery Occlusion.

BACKGROUND: The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied. METHODS: We randomly assigned patients within 6 hours after the estimated time of onset of a stroke due to basilar-artery occlusion, in a 1:1 ratio, to receive endovascular therapy or standard medical care. The primary outcome was a favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death) at 90 days. The primary safety outcomes were symptomatic intracranial hemorrhage within 3 days after the initiation of treatment and mortality at 90 days. RESULTS: A total of 300 patients were enrolled (154 in the endovascular therapy group and 146 in the medical care group). Intravenous thrombolysis was used in 78.6% of the patients in the endovascular group and in 79.5% of those in the medical group. Endovascular treatment was initiated at a median of 4.4 hours after stroke onset. A favorable functional outcome occurred in 68 of 154 patients (44.2%) in the endovascular group and 55 of 146 patients (37.7%) in the medical care group (risk ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.50). Symptomatic intracranial hemorrhage occurred in 4.5% of the patients after endovascular therapy and in 0.7% of those after medical therapy (risk ratio, 6.9; 95% CI, 0.9 to 53.0); mortality at 90 days was 38.3% and 43.2%, respectively (risk ratio, 0.87; 95% CI, 0.68 to 1.12). CONCLUSIONS: Among patients with stroke from basilar-artery occlusion, endovascular therapy and medical therapy did not differ significantly with respect to a favorable functional outcome, but, as reflected by the wide confidence interval for the primary outcome, the results of this trial may not exclude a substantial benefit of endovascular therapy. Larger trials are needed to determine the efficacy and safety of endovascular therapy for basilar-artery occlusion. (Funded by the Dutch Heart Foundation and others; BASICS ClinicalTrials.gov number, NCT01717755; Netherlands Trial Register number, NL2500.).

Ischemic Stroke in Cancer: Mechanisms, Biomarkers, and Implications for Treatment.

Ischemic stroke is an important cause of morbidity and mortality in cancer patients. The underlying mechanisms linking cancer and stroke are not completely understood. Long-standing and more recent evidence suggests that cancer-associated prothrombotic states, along with treatment-related vascular toxicity, such as with chemotherapy and immunotherapy, contribute to an increased risk of ischemic stroke in cancer patients. Novel biomarkers, including coagulation, platelet and endothelial markers, cell-free DNA, and extracellular vesicles are being investigated for their potential to improve risk stratification and patient selection for clinical trials and to help guide personalized antithrombotic strategies. Treatment of cancer-related stroke poses unique challenges, including the need to balance the risk of recurrent stroke and other thromboembolic events with that of bleeding associated with antithrombotic therapy. In addition, how and when to restart cancer treatment after stroke remains unclear. In this review, we summarize current knowledge on the mechanisms underlying ischemic stroke in cancer, propose an etiological classification system unique to cancer-related stroke to help guide patient characterization, provide an overview of promising biomarkers and their clinical utility, and discuss the current state of evidence-based management strategies for cancer-related stroke. Ultimately, a personalized approach to stroke prevention and treatment is required in cancer patients, considering both the underlying cancer biology and the individual patient's risk profile.

Intravenous Thrombolysis 4.5-9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration.

OBJECTIVE: To investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5-9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection. METHODS: Prospective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3-month functional outcome (modified Rankin scale 3-6) and mortality. We compared: (i) IVT >4.5-9 hours versus 0-4.5 hours after stroke onset and (ii) within the >4.5-9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion-weighted imaging fluid-attenuated inversion recovery) versus non-advanced neuroimaging. RESULTS: Of 15,827 patients, 663 (4.2%) received IVT >4.5-9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset-to-treatment time >4.5-9 hours vs onset-to-treatment time 0-4.5 hours), the probability of symptomatic intracranial hemorrhage (ORadjusted 0.80, 95% CI 0.53-1.17), poor functional outcome (ORadjusted 1.01, 95% CI 0.83-1.22), and mortality (ORadjusted 0.80, 95% CI 0.61-1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non-advanced imaging only (9.9% vs 19.7%; ORadjusted 0.51, 95% CI 0.33-0.79). INTERPRETATION: This study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mortality. ANN NEUROL 2023;94:309-320.

Diagnostics Accuracy of Magnetic Resonance Imaging in Detection of Atherosclerotic Plaque Characteristics in Carotid Arteries Compared to Histology: A Systematic Review.

Carotid plaque composition represents one of the main risk factors of future ischemic stroke. MRI provides excellent soft tissue contrast that can distinguish plaque characteristics. Our objective was to analyze the diagnostic accuracy of MRI imaging in the detection of carotid plaque characteristics compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis through a systematic review. After prospective registration in PROSPERO (ID CRD42022329690), Medline Ovid, Embase.com, Cochrane Library, and Web of Science Core were searched without any search limitation up to May 27, 2022 to identify eligible articles. Of the 8168 studies, 53 (37 × 1.5 T MRI, 17 × 3 T MRI) evaluated MRI accuracy in the detection of 13 specific carotid plaque characteristics in 169 comparisons. MRI demonstrated high diagnostic accuracy for detection of calcification (3 T MRI: mean sensitivity 92%/mean specificity 90%; 1.5 T MRI: mean sensitivity 81%/mean specificity 91%), fibrous cap (1.5 T: 89%/87%), unstable plaque (1.5 T: 89%/87%), intraplaque hemorrhage (1.5 T: 86%/88%), and lipid-rich necrotic core (1.5 T: 89%/79%). MRI also proved to have a high level of tissue discrimination for the carotid plaque characteristics investigated, allowing potentially for a better risk assessment and follow-up of patients who may benefit from more aggressive treatments. These results emphasize the role of MRI as the first-line imaging modality for comprehensive assessment of carotid plaque morphology, particularly for unstable plaque. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Prevalence and Factors Associated with Carotid Stenosis in Acute Ischemic Stroke Patients with Atrial Fibrillation.

INTRODUCTION: Among stroke patients with atrial fibrillation (AF), it is not uncommon to identify carotid atherosclerosis. This study aimed to estimate the prevalence of, and factors associated with, carotid atherosclerosis among patients with AF and acute ischemic stroke. PATIENTS AND METHODS: Prospectively collected data from consecutive patients with anterior ischemic stroke and AF who underwent carotid imaging from 10 stroke registries were categorized retrospectively according to the degree of stenosis in: no atherosclerosis, stenosis <50%, stenosis ≥50%, and occlusion. Logistic regression analysis was used to identify factors associated with ipsilateral carotid atherosclerosis. RESULTS: Among 2,955 patients with ischemic stroke and AF, carotid atherosclerosis was evident in 1,022 (34.6%) patients, while carotid stenosis ≥50% and occlusion were identified in 204 (6.9%) and 168 (5.7%) patients, respectively. Ipsilateral carotid stenosis ≥50% or occlusion was associated with higher age (OR: 1.15, 95% CI: 1.01-1.32, per decade), previous ischemic stroke or transient ischemic attack (OR: 1.70, 95% CI: 1.29-2.25), peripheral artery disease (OR: 1.85, 95% CI: 1.23-2.78), coronary artery disease (OR: 1.53, 95% CI: 1.16-2.04), and statin treatment on admission (OR: 1.30, 95% CI: 1.01-1.67). Patients with lacunar stroke had a lower likelihood of stenosis ≥50% or occlusion (OR: 0.29, 95% CI: 0.13-0.68). Compared to the absence of atherosclerotic disease, atherosclerosis in one and two arterial beds was associated with the identification of ipsilateral carotid stenosis (OR: 1.49, 95% CI: 1.22-2.98 and OR: 3.18, 95% CI: 1.85-5.49, respectively). CONCLUSION: Among acute ischemic stroke patients with AF, 1 out of 3 had ipsilateral carotid atherosclerosis, and 1 out of 8 had ipsilateral carotid stenosis ≥50% or occlusion. Atherosclerosis in two arterial beds was the most important predictor for the identification of ipsilateral carotid stenosis. Among ischemic stroke patients with AF, carotid atherosclerosis is common, while carotid imaging should not be overlooked, especially in those with coronary or/and peripheral artery disease.

Service delivery in acute ischemic stroke patients: Does sex matter?

BACKGROUND AND PURPOSE: Women with acute ischemic stroke (AIS) are older and have greater preexisting handicap than men. Given that these factors do not fully explain their poorer long-term outcomes, we sought to investigate potential sex differences in the delivery of acute stroke care in a large cohort of consecutive AIS patients. METHODS: We analyzed all patients from ASTRAL (Acute Stroke Registry and Analysis of Lausanne) from March 2003 to December 2019. Multivariable analyses were performed on acute time metrics, revascularization therapies, ancillary examinations for stroke workup, subacute symptomatic carotid artery revascularization, frequency of change in goals of care (palliative care), and length of hospital stay. RESULTS: Of the 5347 analyzed patients, 45% were biologically female and the median age was 74.6 years. After multiple adjustments, female sex was significantly associated with higher onset-to-door (adjusted hazard ratio [aHR] = 1.09, 95% confidence interval [CI] = 1.04-1.14) and door-to-endovascular-puncture intervals (aHR = 1.15, 95% CI = 1.05-1.25). Women underwent numerically fewer diagnostic examinations (adjusted odds ratio [aOR] = 0.94, 95% CI = 0.85-1.04) and fewer subacute carotid revascularizations (aOR = 0.69, 95% CI = 0.33-1.18), and had longer hospital stays (aHR = 1.03, 95% CI = 0.99-1.07), but these differences were not statistically significant. We found no differences in the rates of acute revascularization treatments, or in the frequency of change of goals of treatments. CONCLUSIONS: This retrospective analysis of a large, consecutive AIS cohort suggests that female sex is associated with unfavorable pre- and in-hospital time metrics, such as a longer onset-to-door and door-to-endovascular-puncture intervals. Such indicators of less effective stroke care delivery may contribute to the poorer long-term functional outcomes in female patients and require further attention.

Undiagnosed major risk factors in acute ischaemic stroke patients: frequency, profile, stroke mechanisms and outcome.

BACKGROUND AND PURPOSE: There is scarce clinical information about the clinical profile of patients with acute ischaemic stroke with previously undiagnosed major vascular risk factors (UMRFs). METHODS: This was a retrospective analysis of data from the Acute Stroke Registry and Analysis of Lausanne registry between 2003 and 2018 with univariate and multivariate logistic regression analyses comparing clinical profiles of patients with UMRFs to patients with at least one previously diagnosed MRF (DMRF). RESULTS: In all, 4354 patients (median age 70 years [interquartile range 15.2], 44.7% female) were included after excluding 763 (14.9%) for lack of consent and three for missing information. Amongst 1125 (25.8%) UMRF patients, 69.7% (n = 784) had at least one newly diagnosed MRF and the others none. The newly detected MRFs were dyslipidaemia (61.4%), hypertension (23.7%), atrial fibrillation (10.2%), diabetes mellitus (5.2%), ejection fraction <35% (2.0%) and coronary disease (1.0%). Comparing UMRF patients to DMRF patients, multivariate analysis showed a positive association with lower age, non-Caucasian ethnicity, contraceptive use (<55 years old), smoking (≥55 years old) and patent-foramen-ovale-related stroke mechanism. A negative association was found with pre-stroke antiplatelet use and higher body mass index. Functional outcome did not differ. Cerebrovascular recurrences were similar between groups. CONCLUSIONS: In this large single-centre cohort, 69.7% of patients with acute ischaemic stroke and UMRF were newly diagnosed with at least one new MRF, the most common being dyslipidaemia, hypertension or atrial fibrillation. Patients of the UMRF group were younger, more often smokers and on contraceptives, and had more patent-foramen-ovale-related strokes.

Acute ischaemic stroke in active cancer versus non-cancer patients: stroke characteristics, mechanisms and clinical outcomes.

BACKGROUND AND PURPOSE: Demographics, clinical characteristics, stroke mechanisms and long-term outcomes were compared between acute ischaemic stroke (AIS) patients with active cancer (AC) versus non-cancer patients. METHODS: Using data from 2003 to 2021 in the Acute STroke Registry and Analysis of Lausanne, a retrospective cohort study was performed comparing patients with AC, including previously known and newly diagnosed cancers, with non-cancer patients. Patients with inactive cancer were excluded. Outcomes were the modified Rankin Scale (mRS) score at 3 months, death and cerebrovascular recurrences at 12 months before and after propensity score matching. RESULTS: Amongst 6686 patients with AIS, 1065 (15.9%) had a history of cancer. After excluding 700 (10.4%) patients with inactive cancer, there were 365 (5.5%) patients with AC and 5621 (84%) non-cancer AIS patients. Amongst AC patients, 154 (42.2%) strokes were classified as cancer related. In multivariable analysis, patients with AC were older (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.00-1.03), had fewer vascular risk factors and were 48% less likely to receive reperfusion therapies (aOR 0.52, 95% CI 0.35-0.76). Three-month mRS scores were not different in AC patients (aOR 2.18, 95% CI 0.96-5.00). At 12 months, death (adjusted hazard ratio 1.91, 95% CI 1.50-2.43) and risk of cerebrovascular recurrence (sub-distribution hazard ratio 1.68, 95% CI 1.22-2.31) before and after propensity score matching were higher in AC patients. CONCLUSIONS: In a large institutional registry spanning nearly two decades, AIS patients with AC had less past cerebrovascular disease but a higher 1-year risk of subsequent death and cerebrovascular recurrence compared to non-cancer patients. Antithrombotic medications at discharge may reduce this risk in AC patients.

Sex differences in acute stroke metrics and outcome dependent on COVID status.

BACKGROUND AND PURPOSE: Biological sex is known to have an impact on quality metrics of acute stroke. We aimed to determine whether COVID positivity accentuates this effect and constitutes worse outcome. METHODS: The present analysis was based on the Global COVID-19 Stroke Registry, a retrospective, international, cohort study of consecutive ischemic stroke patients receiving intravenous thrombolysis and/or endovascular thrombectomy between 1 March 2020 and 30 June 2021. We investigated differences between the sexes in patient characteristics, acute stroke metrics as well as post-stroke outcome in COVID-positive and COVID-negative stroke patients undergoing acute revascularization procedures. RESULTS: A total of 15,128 patients from 106 centers were recorded in the Global COVID-19 Stroke Registry, 853 (5.6%) of whom were COVID-positive. Overall, COVID-positive individuals were treated significantly slower according to every acute stroke metric compared to COVID-negative patients. We were able to show that key quality indicators in acute stroke treatment were unfavorable for COVID-negative women compared to men (last-seen-well-to-door time + 11 min in women). Furthermore, COVID-negative women had worse 3-month outcomes (3-month modified Rankin Scale score [interquartile range] 3.0 [4.0] vs. 2.0 [3.0]; p < 0.01), even after adjusting for confounders. In COVID-positive individuals no such difference between the sexes, either in acute management metrics or in 3-month outcome, was seen. CONCLUSION: Known sex-related differences in acute stroke management exist and extend to times of crisis. Nevertheless, if patients were COVID-19-positive at stroke onset, women and men were treated the same, which could be attributed to structured treatment pathways.

Workflow and Outcome of Thrombectomy in Late Time Window: A Pooled Multicenter Analysis.

BACKGROUND: We investigated the impact of workflow times on the outcomes of patients treated with endovascular thrombectomy (EVT) in the late time window. METHODS: Individual patients' data who underwent EVT in the late time window (onset to imaging >6 hours) were pooled from seven registries and randomized clinical trials. Multiple time intervals were analyzed. Mixed-effects logistic regression was used to estimate the likelihood of functional independence at 90 days (modified Rankin Scale 0-2). Mixed-effects negative binomial regression was used to evaluate the relationship between patient characteristics and workflow time intervals. RESULTS: 608 patients were included. The median age was 70 years (IQR: 58-71), 307 (50.5%) were female, and 310 (53.2%) had wake-up strokes. Successful reperfusion was achieved in 493 (81.2%) patients, and 262 (44.9%) achieved 90-day mRS 0-2. The estimated odds of functional independence decreased by 13% for every 30 minute delay from emergency department (ED) arrival to imaging time and by 7% from ED arrival to the end of EVT in the entire cohort. Also, the estimated odds of functional independence decreased by 33% for every 30 minute delay in the interval from arterial puncture to end of EVT, 16% in the interval from arrival in ED to end of EVT and 6% in the interval from stroke onset to end of EVT among patients who had a wake-up stroke. CONCLUSION: Faster workflow from ED arrival to end of EVT is associated with improved functional independence among stroke patients treated in the late window.

Comparison of atrial septal defect and patent foramen ovale in cryptogenic strokes.

OBJECTIVES: Paradoxical embolism from right-to-left shunt through atrial septal defect (ASD) and patent foramen ovale (PFO) is a well-accepted cause of "cryptogenic" strokes (CS). To better understand the pathogenic role of ASD, we compared ASD patients with CS having a high and low likelihood of being PFO-related. METHODS: In the Acute Stroke Registry and Analysis of Lausanne, we calculated prevalence of PFO and ASD in CS patients undergoing echocardiography, and calculated odds ratios (OR) when compared to non-CS. Using the Risk of Paradoxical Embolism (RoPE) score, we divided CS PFO patients in high (HL-PFO, RoPE 8-10) and low-likelihood (LL-PFO, RoPE 0-4) PFO-related stroke. We then performed univariate comparison of epidemiological, clinical and radiological variables of ASD patients with both PFO groups. RESULTS: Among all CS, prevalence of ASD and PFO were 1.3% and 36.8% respectively. When compared to non-CS, ASD and PFO were associated with CS (OR of 5.2, CI= 1.6-16.6, and 2.8, CI= 2.1-3.8). Compared with HL-PFO, ASD patients were older, more often female, had more cardiovascular risk factors and silent strokes. Compared with LL-PFO, ASD patients were younger, more often female, and had less risk factors. No differences were found for clinical and radiological characteristics and clinical outcome. CONCLUSION: ASD is a rare stroke risk factor for CS. Since characteristics of such patients lie in-between high and low-likelihood paradoxical PFO-strokes, a thorough work-up for other stroke mechanisms is warranted. Individual evaluation of the likelihood of the ASD being causative for stroke may be preferable over routine ASD closure.