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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 ( P interaction =0.312) but did with functional independence ( P interaction =0.010), with a similar trend on excellent outcome ( P interaction =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 ( P interaction =0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 ( P interaction =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., Competing Interests: Disclosures Dr Dabus: consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker; stock holdings in RIST and InNeuroCo. Dr Fifi: consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; stock holdings in Imperative Care and Sim&Cure. Dr Fischer: research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. Dr Haussen: consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB for Jacobs Institute; stock options in viz AI. Dr Herweh: consultancy for Brainomix; speaker with Stryker. Dr Jadhav: consulting with Basking Biosciences; stock options in Gravity Medical Technology; a patent for a novel stent retriever device licensed to Basking Biosciences; and Editor-in-Chief for the Stroke: Vascular and Interventional Neurology journal. Dr Kaesmacher: grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Kaiser: grants from the Joachim Herz Foundation. Dr Kuramatsu: grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. Dr Marto: consulting and speaker fees from Amicus Therapeutics and Boehringer Ingelheim. Dr Michel: grants from the University of Lausanne and SNF. Dr Möhlenbruch: grants from Medtronic, Stryker, and MicroVention. Dr Mokin: stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology; consulting at MicroVention, Medtronic, and Johnson & Johnson. Dr Nagel: consultancy for Brainomix; speaker at Boehringer Ingelheim and Pfizer. Dr Nguyen: Associate Editor of Stroke, advisory board at Aruna Bio and Brainomix. Dr Nogueira: consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; grants from Cerenovus and Stryker. Dr Nolte: research support and compensation from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen; consultancy for Alexion, Daiichi Sankyo, Novartis, AstraZeneca, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. S. Poli: research grants from BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside of the submitted work). Dr Psychogios: grants from Penumbra, Rapid Medical, Medtronic, Phenox, Bangerter-Rhyner Stiftung, SNF, Siemens Healthineers, and Stryker Neurovascular; travel support from Medtronic, Siemens Healthineers, Phenox, Penumbra, and Stryker; consultancy for Siemens Healthineers. Dr Puetz: lecturer for Daiichi Sankyo. Dr Ribo: consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips; stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Ringleb: travel support from Bayer and Bristol Myers Squibb; consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Romoli: research grants from the Italian Stroke Association; consultancy for CSL Behring. Dr Sheth: consultancy for Imperative Care, viz AI, and Penumbra; compensation from Motif Neurosciences (other services); grants from the National Institutes of Health. Dr Siddiqui: ownership stake in Integra Lifesciences and Medtronic; consultancy for Cordis, Rapid Medical, MicroVention, Medtronic Vascular, Vassol, IRRAS USA, Boston Scientific, Amnis Therapeutics, Minnetronix Neuro, Canon Medical Systems USA, Cardinal Health 200, Johnson & Johnson–Latin America, Corindus, Penumbra, Apellis Pharmaceuticals, W.L. Gore & Associates, Stryker Corporation, and viz AI; stock holdings in E8, Spinnaker Medical, Endostream Medical, Cerebrotech Medical Systems, Adona Medical, Bend IT Technologies, Whisper Medical, Neurotechnology Investors, Collavidence, Instylla, Q’Appel Medical, Serenity Medical, Borvo Medical, NeuroRadial Technologies, Sense Diagnostics, Tulavi Therapeutics, Synchron, Neurolutions, Viseon, BlinkTBI, Radical Catheter Technologies, and Truvic Medical; stock options in viz AI, StimMed, Three Rivers Medical, Silk Road Medical, Imperative Care, CVAid Ltd, Cerevatech Medical, InspireMD, PerFlow Medical; security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Inc, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. Dr Strbian: Assistant Editor of Stroke, Editorial Board of European Stroke Journal, advisory board at Boehringer Ingelheim, Alexion/AstraZeneca, and Bristol Myers Squibb/Janssen; research support from Boehringer Ingelheim; consultancies for Orion, Herantis Pharma, and CSL Behring. The other authors report no conflicts.

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., Competing Interests: Disclosures Drs Demeestere and Lemmens reported institutional research fees from Genentech. Dr Strbian reported consultancy fees from AstraZeneca and Boehringer Ingelheim. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda, Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, Ceretrieve; grants from Cerenovus and Stryker. Dr Nagel reported consultancy for Brainomix; speaker with Boehringer ingelheim and Pfizer. Dr Yamagami reported research grants from Bristol Myers Squibb; lecturer’s fees from Stryker, Medtronic, Johnson & Johnson, Bayer, Daiichi Sankyo, Bristol Myers Squibb, Otuska Pharmaceutical; advisory board for Daiichi Sankyo. Dr Puetz reported lecturer for Daiichi Sankyo. Dr Haussen reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; Data Safety and Monitoring Board from Jacobs Institute; and stock options in Viz AI. Dr Ribo reported consultancy for Medtronic, MiniMed, Cerenovus, AptaTargets, Stryker, Philips; stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Michel reported grants from University of Lausanne and Swiss National Science Foundation (SNF). Dr Marto reported consulting from Amicus Therapeutics, Boehringer Ingelheim; Speaker with Boehringer Ingelheim. Dr Henon reported fees from Novartis and a grant from Sanofi-Aventis. Dr Gutierrez reported consultancy fees from Medtronic, Stryker and Microvention, and a grant from Methinks, Microvention, Stryker and the National Institutes of Health. Dr Siegler reported a grant from Philips and Viz AI. Dr Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, CSL Behring; lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer Ingelheim, Daiichi Sankyo, Bayer and Bristol-Meyers Squibb. Dr Sheth reported consultancy for Imperative Care, Viz AI, Penumbra; compensation from Motif Neurosciences; grants from National Institutes of Health. Dr Dobrocky reported consultancy fees from MicroVention. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Zaidi reported a grant from Genentech. Dr Castonguay reported employment by Medtronic. Dr Uchida reported fees by Bristol Myers Squibb, Daiichi Sankyo, Medtronic and Stryker. Dr Sakai reported research grant from Biomedical Solutions, Medtronic, Terumo, TG Medical; lecturer’s fees from Asahi-Intec, Biomedical Solutions, Daiichi Sankyo, Kaneka, Medtronic, Terumo; advisory board for Johnson & Johnson, Medtronic, Terumo. Dr Toyoda reported lecturer fees from Otsuka, Daiichi Sankyo, Bayer, Novartis, and Bristol-Myers Squibb. Dr Kaiser reported grants from the Joachim Herz Foundation. Dr Möhlenbruch reported grants from Medtronic, Stryker, and MicroVention. Dr Ringleb reported travel support from Bayer and Bristol Myers Squibb; consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Zaidat reported consultancy fees by Johnson & Johnson, Medtronic and Stryker, Penumbra stock, and a grant from Johson & Johnson, Medtronic, Penumbra and Stryker. Dr Fischer reported research support from SNF, Medtronic, Stryker, Rapid Medical, Penumbra, Phenox; consultancies for Stryker, CSL Behring; advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, Acthera. Dr Nguyen discloses research support from Medtronic to her institution; advisory board for Brainomix, Aruna Bio; Associate Editor Stroke.

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% ( P unadj <0.05), but it decreased in the subacute phase from 79.0% to 60.1% ( P adj =0.32) and thrombolysis in stroke mimics decreased by half (8.6% versus 4.3%; P <0.05). Rates of unidentified stroke mechanism at hospital discharge were similar (22.8% versus 28.1%; adj <0.05). The rates of initially missed AIS diagnosis was similar (3.8% versus 4.4%, P adj =0.32) and thrombolysis in stroke mimics decreased by half (8.6% versus 4.3%; P adj <0.05). Rates of unidentified stroke mechanism at hospital discharge were similar (22.8% versus 28.1%; P adj =0.99). The length of hospitalization decreased from 9 (interquartile range, 6-14) to 7 (interquartile range, 4-12) days ( P adj =0.62). Disability at 3 months was similar (common adjusted odds ratio for favorable Rankin shift, 0.98 [95% CI, 0.71-1.36]; P adj =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., Competing Interests: Disclosures None.

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., Competing Interests: Disclosures Dr Castonguay reports employment by Medtronic. Dr Cordonnier reports compensation from the University of Glasgow for data and safety monitoring services; employment by the University of Lille; compensation from Biogen for consultant services. Dr Fischer reports employment by Universität Basel; compensation from Boehringer Ingelheim and Biogen for expert witness services. Dr Dobrocky reported MicroVention consultancy. Dr Haussen reports compensation from Vesalio, Cerenovus, Chiesi USA, Inc, Stryker, Brainomix, and Poseydon Medical for consultant services; stock options in Viz.ai; compensation from Jacobs Institute for data and safety monitoring services. Dr Henon reports grants from Sanofi-Aventis U.S. LLC. Dr Kaesmacher reports grants from Swiss National Science Foundation to other. Dr Kaiser reported grants from Joachim Herz Foundation. Martinez-Majander reported grants from Finnish Medical Foundation. Dr Marto reported consulting from Amicus Therapeutics and Boehringer Ingelheim; Speaker with Boehringer Ingelheim. Dr Michel reports grants from the Swiss National Science Foundation, Swiss Heart Foundation, and the University of Lausanne to other. Dr Möhlenbruch reports grants from Medtronic, MicroVention, Inc, and Stryker to other. Dr Nagel reports compensation from Brainomix for consultant services. Dr Nguyen discloses research support from Medtronic, Society of Vascular, and Interventional Neurology to her institution; advisory board compensation from Idorsia, Brainomix; Associate Editor of Stroke. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda, Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz.ai, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, RapidPulse; stock options Viz.ai, Vesalio, Perfuze, Corindus, Brainomix, Ceretrieve; grants from Cerenovus, Stryker; Dr Nogueira reports compensation from Philips for consultant services; stock holdings in Quantanosis AI; compensation from Synchron for data and safety monitoring services; stock holdings in Piraeus Medical; stock options in Viseon, Inc; compensation from Hybernia for consultant services; stock options in Reist/Q’Apel Medical; stock options in Cerebrotech; compensation from Astrocyte and Cerebrotech for consultant services; stock holdings in Brain4Care; stock options in Truvic. Dr Ortega-Gutierrez reports compensation from MicroVention, Inc, Medtronic, and Stryker for consultant services; grants from Stryker, National Institutes of Health, methinks, Siemens, and MicroVention, Inc; and employment by Carver College of Medicine, University of Iowa. Dr Puetz reported as lecturer for Daiichi Sankyo. Dr Puri reports compensation from Medtronic, Stryker, Johnson & Johnson Health Care Systems, Inc, and MicroVention, Inc, for consultant services. Dr Ribo reports compensation from Philips, Stryker Corporation, Cerenovus, Medtronic MiniMed, Inc, and AptaTargets for consultant services; stock holdings in Anaconda Biomed, Methinks, and Nora. Dr Ringleb reports compensation from Daiichi Sankyo Company and Boehringer Ingelheim for consultant services; employment by Heidelberg University Hospital; travel support from Bristol-Myers Squibb and Bayer Healthcare. Dr Sakai reports compensation from Stryker, Asahi Intecc Co, Ltd, Terumo, Medtronic, Johnson & Johnson Medical Devices & Diagnostics Group, Latin America, L.L.C., Daiichi Sankyo Company Ltd, and Kaneka Medics for other services; grants from Medtronic; grants from Terumo. Dr Sheth reports compensation from Motif Neurosciences for other services; compensation from Viz.ai, Imperative Care, Inc, and Penumbra, Inc, for consultant services; grants from National Institutes of Health; employment by UTHealth McGovern Medical School. Dr Strbian reports employment by Helsingin ja Uudenmaan Sairaanhoitopiiri. Dr Uchida reports compensation from Bristol-Myers Squibb, Stryker, Daiichi Sankyo Company, Ltd, and Medtronic for other services. Dr Wouters reports grants from The Research Foundation-Flanders travel and Remmert Adriaan-Laan-Fonds. Dr Yamagami reports compensation from Otsuka Pharmaceutical Co, Ltd. Medtronic, Daiichi Sankyo Company Ltd, Bristol-Myers Squibb, Johnson and Johnson, Bayer. Daiichi Sankyo Company Ltd, and Stryker for other services; grants from Bristol-Myers Squibb. S. Yoshimura reports compensation from Bristol-Myers Squibb, Johnson & Johnson Medical Devices & Diagnostics Group, Latin America, LLC, Bayer, Kaneka Medics, Boehringer Ingelheim, Medtronic Daiichi Sankyo Company, Stryker, and Terumo for other services. S. Ning discloses research support from Society for Interventional Radiology. Dr Zaidat reports grants from Medtronic, Penumbra, Inc, Johnson and Johnson, Stryker to other; compensation from Medtronic and Johnson & Johnson Health Care Systems, Inc, and Penumbra, Inc, for consultant services; stock holdings in Penumbra Inc. The other authors report no conflicts.

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., Competing Interests: Disclosures Dr Nguyen is on the Advisory Board of Idorsia. Dr Michel received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and the University of Lausanne. The other authors report no conflicts. Global COVID-19 Stroke Registry: R. Herzig received research grants from the Ministry of Health of the Czech Republic (Grant number DRO – UHHK 00179906) and Charles University, Czech Republic (Cooperatio Program). C. Nolte received research grants from the German Ministry of Research and Education, the German Center for Neurodegenerative Diseases, and the German Center for Cardiovascular Research and is a speaker and advisory for Abbott, Alexion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer Pharma. S. Tjoumakaris is on Advisory Medtronic and MicroVention. J. Min is on Advisory Medtronic and Abbott. M.-A. Khan received research grants from National Institutes of Health, Spectrum Health-Michigan State University Research Alliance, and Genentech. A. Zini received consultation and travel expenses from Alexion-AstraZeneca, CSL Behring, and Boehringer Ingelheim and is on the steering committee of the OCEANIC-STROKE trial (A Study to Test Asundexian to Prevent a Clot-Related Stroke in Participants After an Acute Ischemic Stroke or High-Risk TIA/Mini-Stroke). A. Slowik and P. Wrona received research grant from European Research Area Network (ERA-NET) - Network of European Funding for Neuroscience Research (NEURON)/21/2020 Identification and clinical validation of biomarkers for long-term outcome after cerebral ischaemia (iBioStroke).

Background: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion., Methods: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale., Results: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P =0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P =0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P =0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P =0.0001; mortality, 10.1% versus 5.0%; P =0.002)., Conclusions: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted., Competing Interests: Disclosures Dr Asdaghi reported employment by the American Heart Association. Dr Dabus reported consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker and stock holdings in RIST and InNeuroCo. Dr Fifi reported consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; and stock holdings in Imperative Care and Sim&Cure. Dr Fischer reported research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; and is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. Dr Finitsis reports patent US11166738B2. Dr Haussen reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB from Jacobs Institute; and stock options in Viz AI. Dr Herweh reported consultancy for Brainomix and Speaker with Stryker. Dr Jadhav reports consulting with Basking Biosciences; stock options in Gravity Medical Technology; and a patent for a novel stent retriever device licensed to Basking Biosciences. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Kaiser reported grants from the Joachim Herz Foundation. Dr Kuramatsu reports grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. Dr Pedro Marto reported consulting from Amicus Therapeutics and Boehringer Ingelheim and Speaker with Boehringer Ingelheim. Dr Michel reported grants from the University of Lausanne and Swiss National Science Foundation (SNF). Dr Möhlenbruch reported grants from Medtronic, Stryker, and MicroVention. Dr Mokin reported stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology and consulting from MicroVention, Medtronic, and Johnson & Johnson. Dr Nagel reported consultancy for Brainomix and is a speaker with Boehringer Ingelheim and Pfizer. Dr Nguyen reported research support from Society of Vascular and Interventional Neurology (SVIN) and Medtronic and is on the advisory board with Idorsia. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; and grants from Cerenovus and Stryker. Dr Nolte reported compensation (other services) from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen and consultancy for Daiichi Sankyo, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. Dr Psychogios reported grants from Penumbra, Rapid Medical, Medtronic, Phenox, Bangerter-Rhyner Stiftung, SNF, Siemens Healthineers, and Stryker Neurovascular; travel support from Medtronic, Siemens Healthineers, Phenox, Penumbra, and Stryker; and consultancy for Siemens Healthineers. Dr Puetz reported being a lecturer for Daiichi Sankyo. Dr Ribo reported consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips and stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Ringleb reported travel support from Bayer and Bristol Myers Squibb and consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Sheth reported consultancy for Imperative Care, Viz AI, and Penumbra; compensation from Motif Neurosciences (other services); and grants from the National Institutes of Health. Dr Siddiqui reported an ownership stake in Integra Lifesciences and Medtronic; consultancy for Cordis, Rapid Medical, MicroVention, Medtronic Vascular, Vassol, IRRAS USA, Boston Scientific, Amnis Therapeutics, Minnetronix Neuro, Canon Medical Systems USA, Cardinal Health 200, Johnson & Johnson–Latin America, Corindus, Penumbra, Apellis Pharmaceuticals, W.L. Gore & Associates, Stryker Corporation, and Viz AI; stock holdings in E8, Spinnaker Medical, Endostream Medical, Cerebrotech Medical Systems, Adona Medical, Bend IT Technologies, Whisper Medical, Neurotechnology Investors, Collavidence, Instylla, Q’Appel Medical, Serenity Medical, Borvo Medical, NeuroRadial Technologies, Sense Diagnostics, Tulavi Therapeutics, Synchron, Neurolutions, Viseon, BlinkTBI, Radical Catheter Technologies, and Truvic Medical; stock options in Viz AI, StimMed, Three Rivers Medical, Silk Road Medical, Imperative Care, CVAID, Cerevatech Medical, InspireMD, and PerFlow Medical; and security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. The other authors report no conflicts.

Background: Little is known on the role of mismatch profile in patients undergoing early endovascular treatment (EVT). We aimed to describe pretreatment perfusion parameters and mismatch profiles in anterior circulation large vessel occlusion acute ischemic stroke undergoing EVT in the early time window and assess their association with time from stroke onset and outcomes., Methods: Retrospective single-center study, including early (<6 hours) EVT-treated large vessel occlusion acute ischemic stroke with baseline perfusion data, assessing perfusion parameters (ischemic core volume, mismatch volume and mismatch ratio) and mismatch profiles (favorable versus unfavorable, based on criteria adopted in EXTEND-IA [Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial], SWIFT PRIME [Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment], DEFUSE 3 [Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3], and DAWN [Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo] trials). We evaluated their association with time from stroke onset (r s [for parameters] or χ 2 for trend [for profiles]) and association with modified Rankin Scale score >2, symptomatic intracranial hemorrhage, and mortality (multivariate regression analyses [each parameter/profile entered into a separate logistic regression model, adjusted for baseline variables associated with each outcome in the univariate analysis at the P <0.1 level])., Results: Among 357 patients, unfavorable mismatch profiles ranged from 21% to 60%, depending on the criterion, and were not correlated with time from stroke onset ( P =0.490). All individual perfusion parameters and unfavorable mismatch profiles were associated with poor functional outcome: ischemic core volume adjusted odds ratio (aOR), 1.49 ([95% CI, 1.13-1.97] P =0.005); penumbral volume aOR, 0.30 ([95% CI, 0.10-0.84] P =0.022); mismatch ratio aOR, 0.67 ([95% CI, 0.50-0.90] P =0.007); EXTEND-IA aOR, 2.61 ([95% CI, 1.23-5.51] P =0.012); SWIFT PRIME aOR, 2.50 ([95% CI, 1.30-4.57] P =0.006); DEFUSE 3 aOR, 2.28 ([95% CI, 1.14-4.57] P =0.020); and DAWN aOR, 4.19 ([95% CI, 2.13-8.26] P <0.001). EXTEND-IA and DEFUSE 3 unfavorable profiles were also independently associated with symptomatic intracranial hemorrhage (aOR, 3.82 [95% CI, 1.42-10.3]; P =0.008 and aOR, 2.83 [95% CI, 1.09-7.36]; P =0.033) and death (aOR, 3.26 [95% CI, 1.33-8.02]; P =0.010 and aOR, 2.52 [95% CI, 1.10-5.82]; P =0.030)., Conclusions: Pretreatment perfusion parameters and mismatch profiles in early EVT-treated patients were not correlated with time from stroke onset but were independently associated with functional outcome. Mismatch assessment in the early time window may improve EVT patient selection, independently of onset-to-treatment time.

Background: Whether endovascular therapy (EVT) added on best medical management (BMM), as compared to BMM alone, is beneficial in acute ischemic stroke with isolated posterior cerebral artery occlusion is unknown., Methods: We conducted a multicenter international observational study of consecutive stroke patients admitted within 6 hours from symptoms onset in 26 stroke centers with isolated occlusion of the first (P1) or second (P2) segment of the posterior cerebral artery and treated either with BMM+EVT or BMM alone. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month good functional outcome (modified Rankin Scale [mRS] score 0-2 or return to baseline modified Rankin Scale). Secondary outcomes were 3-month excellent recovery (modified Rankin Scale score 0-1), symptomatic intracranial hemorrhage, and early neurological deterioration., Results: Overall, 752 patients were included (167 and 585 patients in the BMM+EVT and BMM alone groups, respectively). Median age was 74 (interquartile range, 63-82) years, 329 (44%) patients were female, median National Institutes of Health Stroke Scale was 6 (interquartile range 4-10), and occlusion site was P1 in 188 (25%) and P2 in 564 (75%) patients. Baseline clinical and radiological data were similar between the 2 groups following propensity score weighting. EVT was associated with a trend towards lower odds of good functional outcome (odds ratio, 0.81 [95% CI, 0.66-1.01]; P =0.06) and was not associated with excellent functional outcome (odds ratio, 1.17 [95% CI, 0.95-1.43]; P =0.15). EVT was associated with a higher risk of symptomatic intracranial hemorrhage (odds ratio, 2.51 [95% CI, 1.35-4.67]; P =0.004) and early neurological deterioration (odds ratio, 2.51 [95% CI, 1.64-3.84]; P <0.0001)., Conclusions: In this observational study of patients with proximal posterior cerebral artery occlusion, EVT was not associated with good or excellent functional outcome as compared to BMM alone. However, EVT was associated with higher rates of symptomatic intracranial hemorrhage and early neurological deterioration. EVT should not be routinely recommended in this population, but randomization into a clinical trial is highly warranted.

Background: Reperfusion without functional independence (RFI) is an undesired outcome following thrombectomy in acute ischemic stroke. The primary objective was to evaluate, in patients presenting with proximal anterior circulation occlusion stroke in the extended time window, whether selection with computed tomography (CT) perfusion or magnetic resonance imaging is associated with RFI, mortality, or symptomatic intracranial hemorrhage (sICH) compared with noncontrast CT selected patients., Methods: The CLEAR study (CT for Late Endovascular Reperfusion) was a multicenter, retrospective cohort study of stroke patients undergoing thrombectomy in the extended time window. Inclusion criteria for this analysis were baseline National Institutes of Health Stroke Scale score ≥6, internal carotid artery, M1 or M2 segment occlusion, prestroke modified Rankin Scale score of 0 to 2, time-last-seen-well to treatment 6 to 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction 2c-3)., Results: Of 2304 patients in the CLEAR study, 715 patients met inclusion criteria. Of these, 364 patients (50.9%) showed RFI (ie, mRS score of 3-6 at 90 days despite successful reperfusion), 37 patients (5.2%) suffered sICH, and 127 patients (17.8%) died within 90 days. Neither imaging selection modality for thrombectomy candidacy (noncontrast CT versus CT perfusion versus magnetic resonance imaging) was associated with RFI, sICH, or mortality. Older age, higher baseline National Institutes of Health Stroke Scale, higher prestroke disability, transfer to a comprehensive stroke center, and a longer interval to puncture were associated with RFI. The presence of M2 occlusion and higher baseline Alberta Stroke Program Early CT Score were inversely associated with RFI. Hypertension was associated with sICH., Conclusions: RFI is a frequent phenomenon in the extended time window. Neither magnetic resonance imaging nor CT perfusion selection for mechanical thrombectomy was associated with RFI, sICH, and mortality compared to noncontrast CT selection alone., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04096248.

Background: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly., Methods: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models., Results: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratio adjusted 1.14 [0.83-1.57]) did not differ significantly between both groups. However, the probability of death (odds ratio adjusted 3.77 [3.14-4.53]) and poor functional outcome (odds ratio adjusted 2.63 [2.13-3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar., Conclusions: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.

Background: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with large vessel occlusion is unknown. Perfusion imaging may identify subsets of large vessel occlusion-related minor stroke patients with distinct response to bridging therapy., Methods: We conducted a multicenter international observational study of consecutive IVT-treated patients with minor stroke (National Institutes of Health Stroke Scale score ≤5) who had an anterior circulation large vessel occlusion and perfusion imaging performed before IVT, with a subset undergoing immediate thrombectomy. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month modified Rankin Scale score 0 to 1. We searched for an interaction between treatment group and mismatch volume (critical hypoperfusion-core volume)., Results: Overall, 569 patients were included (172 and 397 in the bridging therapy and IVT groups, respectively). After propensity-score weighting, the distribution of baseline variables was similar across the 2 groups. In the entire population, bridging was associated with lower odds of achieving modified Rankin Scale score 0 to 1: odds ratio, 0.73 [95% CI, 0.55-0.96]; P =0.03. However, mismatch volume modified the effect of bridging on clinical outcome ( P interaction =0.04 for continuous mismatch volume); bridging was associated with worse outcome in patients with, but not in those without, mismatch volume <40 mL (odds ratio, [95% CI] for modified Rankin Scale score 0-1: 0.48 [0.33-0.71] versus 1.14 [0.76-1.71], respectively). Bridging was associated with higher incidence of symptomatic intracranial hemorrhage in the entire population, but this effect was present in the small mismatch subset only ( P interaction =0.002)., Conclusions: In our population of large vessel occlusion-related minor stroke patients, bridging therapy was associated with lower rates of good outcome as compared with IVT alone. However, mismatch volume was a strong modifier of the effect of bridging therapy over IVT alone, notably with worse outcome with bridging therapy in patients with mismatch volume ≤40 mL. Randomized trials should consider adding perfusion imaging for patient selection.

Background: We recently reported a worrying 30% rate of early neurological deterioration (END) occurring within 24 hours following intravenous thrombolysis (IVT) in minor stroke with isolated internal carotid artery occlusion (ie, without additional intracranial occlusion), mainly due to artery-to-artery embolism. Here, we hypothesize that in this setting IVT-as compared to no-IVT-may foster END, in particular by favoring artery-to-artery embolism from thrombus fragmentation., Methods: From a large multicenter retrospective database, we compared minor stroke (National Institutes of Health Stroke Scale score <6) isolated internal carotid artery occlusion patients treated within 4.5 hours of symptoms onset with either IVT or antithrombotic therapy between 2006 and 2020 (inclusion date varied among centers). Primary outcome was END within 24 hours (≥4 National Institutes of Health Stroke Scale points increase within 24 hours), and secondary outcomes were END within 7 days (END 7d ) and 3-month modified Rankin Scale score 0 to 1., Results: Overall, 189 patients were included (IVT=95; antithrombotics=94 [antiplatelets, n=58, anticoagulants, n=36]) from 34 centers. END within 24 hours and END 7d occurred in 46 (24%) and 60 (32%) patients, respectively. Baseline clinical and radiological variables were similar between the 2 groups, except significantly higher National Institutes of Health Stroke Scale (median 3 versus 2) and shorter onset-to-imaging (124 versus 149min) in the IVT group. END within 24 hours was more frequent following IVT (33% versus 16%, adjusted hazard ratio, 2.01 [95% CI, 1.07-3.92]; P =0.03), driven by higher odds of artery-to-artery embolism (20% versus 9%, P =0.09). However, END 7d and 3-month modified Rankin Scale score of 0 to 1 did not significantly differ between the 2 groups (END 7d : adjusted hazard ratio, 1.29 [95% CI, 0.75-2.23]; P =0.37; modified Rankin Scale score of 0-1: adjusted odds ratio, 1.1 [95% CI, 0.6-2.2]; P =0.71). END 7d occurred earlier in the IVT group: median imaging-to-END 2.6 hours (interquartile range, 1.9-10.1) versus 20.4 hours (interquartile range, 7.8-34.4), respectively, P <0.01., Conclusions: In our population of minor strokes with iICAO, although END rate at 7 days and 3-month outcome were similar between the 2 groups, END-particularly END due to artery-to-artery embolism-occurred earlier following IVT. Prospective studies are warranted to further clarify the benefit/risk profile of IVT in this population.

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain., Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment., Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0-1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0-5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0-1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4-14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4-5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8-1.7])., Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Certain drugs may increase the risk of ischemic stroke (IS). Our goal was to review associations between frequently used drugs and IS. We created an initial list of frequently used drugs to search Pubmed/MEDLINE from 1966 to 2020 and reviewed phase III and IV data, case series, and drug authorities' safety warnings to assess a potential association with IS. Drugs were grouped according to the World Health Organization Anatomical Therapeutic Chemical Classification System. Predefined criteria were applied to establish a level of evidence for an association, from A (high level of evidence of association) to E (high level of evidence of absence of association). In addition, we assessed relative risks and reviewed potential mechanisms of IS facilitation. We assessed 81 drugs or drug classes from 11 World Health Organization Anatomical Therapeutic Chemical Groups. We identified a high level of association for erythropoietin, combined contraceptives, oral estrogen replacement therapy, bevacizumab, tamoxifen, and antipsychotics and a moderate level for ponatinib, nilotinib, darunavir, and gonadotropin-releasing hormone agonists. Drug dose and treatment duration may modify the risk. For a substantial number of drugs, we found no association, and for others, there were insufficient data to categorize risk. We identified a high level of association of IS with a limited number of drugs, a potential association with some, and a lack of data for others. The summarized information may help clinicians to estimate the contribution of a drug to an IS, to better assess drug benefit-risk ratios, and to support decisions about using specific drugs.

Background and Purpose: The Risk of Paradoxical Embolism (RoPE) score stratifies patients with stroke according to the probability of having a patent foramen ovale (PFO), which (through Bayes theorem and simple assumptions) can be used to estimate the probability that a PFO is pathogenic in a given subgroup of patients with specific features (ie, a given RoPE score value): a higher PFO prevalence corresponds to a higher probability that a PFO is pathogenic. Among alternative mechanisms in embolic stroke of undetermined source (ESUS), the actual stroke cause may be covert atrial fibrillation. We aimed to validate the RoPE score in a large ESUS population and investigate the rate of stroke recurrence and new incident atrial fibrillation during follow-up according to PFO status and RoPE score., Methods: We pooled data of consecutive patients with ESUS from 3 prospective stroke registries. We assessed RoPE score’s calibration and discrimination for the presence of PFO (and consequently for the probability that it is pathogenic). Multivariate logistic regression analysis was performed to identify factors associated with PFO., Results: Among 455 patients with ESUS (median age 59 years), 184 (40%) had PFO. The RoPE score’s area under the receiver operating characteristic curve was 0.75. In addition to RoPE score variables, absence of left ventricular hypertrophy, absence of atherosclerosis, and infratentorial lesions were independently associated with PFO. In patients with PFO and RoPE 7 to 10, PFO and RoPE 0 to 6, and without PFO, new incident atrial fibrillation rate was 3.1%, 20.5%, and 31.8%, respectively (log-rank test=6.28, P=0.04). Stroke recurrences in patients with likely pathogenic PFO were not statistically different from other patients., Conclusions: This multicenter study validates the RoPE score to predict the presence/absence of PFO in patients with ESUS, which strongly suggests that RoPE score is helpful in identifying patients with ESUS with pathogenic versus incidental PFOs. Left ventricular hypertrophy, atherosclerosis, and infratentorial stroke may further improve the score. Low RoPE scores were associated with more incidental atrial fibrillation during 10-year follow-up.

Background and Purpose: Endovascular treatment (EVT) in acute ischemic stroke is effective in the late time window in selected patients. However, the frequency and clinical impact of procedural complications in the early versus late time window has received little attention., Methods: We retrospectively studied all acute ischemic strokes from 2015 to 2019 receiving EVT in the Acute Stroke Registry and Analysis of Lausanne. We compared the procedural EVT complications in the early (<6 hours) versus late (6-24 hours) window and correlated them with short-term clinical outcome., Results: Among 695 acute ischemic strokes receiving EVT (of which 202 were in the late window), 113 (16.3%) had at least one procedural complication. The frequency of each single, and for overall procedural complications was similar for early versus late EVT (16.2% versus 16.3%, P =0.90). Procedural complications lead to a significantly less favorable short-term outcome, reflected by the absence of National Institutes of Health Stroke Scale improvement in late EVT (delta-National Institutes of Health Stroke Scale-24 hours, -2.5 versus 2, adj =0.90). Procedural complications lead to a significantly less favorable short-term outcome, reflected by the absence of National Institutes of Health Stroke Scale improvement in late EVT (delta-National Institutes of Health Stroke Scale-24 hours, -2.5 versus 2, P adj =0.01)., Conclusions: In this retrospective analysis of consecutive EVT, the frequency of procedural complications was similar for early and late EVT patients but very short-term outcome seemed less favorable in late EVT patients with complications.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P =0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P <0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Background and Purpose- The HAVOC score (hypertension, age, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, coronary artery disease) was proposed for the prediction of atrial fibrillation (AF) after cryptogenic stroke. It showed good model discrimination (area under the curve, 0.77). Only 2.5% of patients with a low-risk HAVOC score (ie, 0-4) were diagnosed with new incident AF. We aimed to assess its performance in an external cohort of patients with embolic stroke of undetermined source. Methods- In the AF-embolic stroke of undetermined source dataset, we assessed the discriminatory power, calibration, specificity, negative predictive value, and accuracy of the HAVOC score to predict new incident AF. Patients with a HAVOC score of 0 to 4 were considered as low-risk, as proposed in its original publication. Results- In 658 embolic stroke of undetermined source patients (median age, 67 years; 44% women), the median HAVOC score was 2 (interquartile range, 3). There were 540 (82%) patients with a HAVOC score of 0 to 4 and 118 (18%) with a score of ≥5. New incident AF was diagnosed in 95 (14.4%) patients (28.8% among patients with HAVOC score ≥5 and 11.3% among patients with HAVOC score 0-4 [age- and sex-adjusted odds ratio, 2.29 (95% CI, 1.37-3.82)]). The specificity of low-risk HAVOC score to identify patients without new incident AF was 88.7%. The negative predictive value of low-risk HAVOC score was 85.1%. The accuracy was 78.0%, and the area under the curve was 68.7% (95% CI, 62.1%-73.3%). Conclusions- The previously reported low rate of AF among embolic stroke of undetermined source patients with low-risk HAVOC score was not confirmed in our cohort. Further assessment of the HAVOC score is warranted before it is routinely implemented in clinical practice.

Background and Purpose- We investigated efficacy and safety of acute revascularization with intravenous thrombolysis (IVT) and endovascular treatment (EVT) in ischemic stroke from isolated posterior cerebral artery occlusion, by assessing recanalization, disability, visual, cognitive outcomes, and hemorrhagic complications. Methods- For this retrospective single-center cohort study, we selected all consecutive patients with stroke with isolated posterior cerebral artery occlusion from the Acute Stroke Registry and Analysis of Lausanne registry between January 2003 and July 2018, and compared (1) IVT with conservative treatment (CTr) and (2) EVT to best medical therapy (BMT, ie, CTr or IVT) in terms of 3-month disability and visual field defect, and cognitive domains impaired after stroke. Unadjusted analysis, multivariable logistic regression, and propensity score matched analyses were performed. Results- Among 106 patients with isolated posterior cerebral artery occlusion, 21 received EVT (13 bridging), 34 IVT alone, and 51 CTr. Median age was 76 years, 47% were female and median National Institutes of Health Stroke Scale score was 7. Complete 24-hour recanalization was more frequent with IVT than CTr (51% versus 9%; OR [95% CI]=10.62 [2.13-52.92]) and with EVT compared with BMT (68% versus 34%; OR [95% CI]=4.11 [1.35-12.53]). Higher proportions of good disability, visual and cognitive outcomes were observed in IVT versus CTr, adj ORs (95% CI)=1.65 (0.60-4.52), 2.01 (0.58-7.01), 2.94 (0.35-24.4), respectively, and in EVT versus BMT, adj ORs (95% CI)=1.44 (0.51-4.10), 4.28 (1.00-18.29), 4.37 (0.72-26.53), respectively. Hemorrhagic complications and mortality did not increase with IVT or EVT. Conclusion s-We show increased odds of recanalization following IVT and even higher after EVT. We observed a trend for a positive effect on disability, visual, and cognitive outcomes with IVT over CTr and with EVT over BMT.

Background and Purpose- Early arterial recanalization is a strong determinant of prognosis in acute ischemic stroke. Nevertheless, reocclusion can occur after initial recanalization. We assessed associated factors and long-term prognosis of reocclusion after successful mechanical thrombectomy (MT). Methods- From the prospectively constructed Acute Stroke Registry and Analysis of Lausanne cohort, we included consecutive patients with anterior and posterior circulation strokes treated by successful MT (modified treatment in cerebral infarction 2b-3) and with 24-hour vascular imaging available. Reocclusion at this time-point was defined as new intracranial occlusion within an arterial segment recanalized at the end of MT. Through multivariate logistic regression, we investigated associated factors and 3-months outcome. In a 4:1 matched-cohort, we also assessed the role of residual thrombus or stenosis on post-recanalization angiographic images as potential predictor of reocclusion. Results- Among 473 patients with successful recanalization, 423 (89%) were included. Of these, 28 (6.6%) had 24-hour reocclusion. Preadmission statin therapy (aOR [adjusted odds ratio], 0.27; 95% CI, 0.08-0.94), intracranial internal carotid artery occlusion (aOR, 3.53; 95% CI, 1.50-8.32), number of passes (aOR, 1.31; 95% CI, 1.06-1.62), transient reocclusion during MT (aOR, 8.55; 95% CI, 2.14-34.09), and atherosclerotic cause (aOR, 3.14; 95% CI, 1.34-7.37) were independently associated with reocclusion. In the matched-cohort analysis, residual thrombus or stenosis was associated with reocclusion (aOR, 15.6; 95% CI, 4.6-52.8). Patients experiencing reocclusion had worse outcome (aOR, 5.0; 95% CI, 1.2-20.0). Conclusions- Reocclusion within 24-hours of successful MT was independently associated with statin pretreatment, occlusion site, more complex procedures, atherosclerotic cause, and residual thrombus or stenosis after recanalization. Reocclusion impact on long-term outcome highlights the need to monitor and prevent this early complication.

Background and Purpose- Early arterial recanalization in acute ischemic stroke is strongly associated with better outcomes. However, early worsening of arterial patency was seldom studied. We investigated potential predictors and long-term prognosis of worsening of arterial patency at 24 hours after stroke onset. Methods- Patients from the Acute Stroke Registry and Analysis of Lausanne registry including admission and 24-hour vascular imaging (computed tomography or magnetic resonance angiography) were included. Worsening of arterial patency was defined as a new occlusion and significant stenosis in any extracranial or intracranial artery, comparing 24 hours with admission imaging. Variables associated with worsening of arterial patency were assessed by stepwise multiple logistic regression. The impact of arterial worsening on 3-month outcome was investigated with an adjusted modified Rankin Scale shift analysis. Results- Among 2152 included patients, 1387 (64.5%) received intravenous thrombolysis and endovascular treatment, and 65 (3.0%) experienced 24-hour worsening of arterial patency. In multivariable analysis, history of hypertension seemed protective (adjusted odds ratio [aOR], 0.45; 95% CI, 0.27-0.75) while higher admission National Institutes of Health Stroke Scale (aOR, 1.06; 95% CI, 1.02-1.10), intracranial (aOR, 4.78; 95% CI, 2.03-11.25) and extracranial stenosis (aOR, 3.67; 95% CI, 1.95-6.93), and good collaterals (aOR, 3.71; 95% CI, 1.54-8.95) were independent predictors of worsening of arterial patency. Its occurrence was associated with a major unfavorable shift in the distribution of the modified Rankin Scale at 3 months (aOR, 5.97; 95% CI, 3.64-9.79). Conclusions- Stroke severity and admission vascular imaging findings may help to identify patients at a higher risk of developing worsening of arterial patency at 24 hours. The impact of worsening of arterial patency on long-term outcome warrants better methods to detect and prevent this early complication.

Background and Purpose- We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods- We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results- In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99-1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87-1.73) or categorical covariate (likelihood-ratio test 2.59, P=0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR ≥90, 16.6% for eGFR 60-89, 21.7% for eGFR 45-59, 19.2% for eGFR 30-44, and 24.9% for eGFR <30 (likelihood-ratio test 2.59, P=0.63). The results were similar for the outcome of death. Conclusions- The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.