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• W4200430734 abstract "HomeStrokeVol. 53, No. 1Advances in Stroke: Treatments-Interventional Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBAdvances in Stroke: Treatments-Interventional Bruce C.V. Campbell, MBBS, PhD and Thanh N. Nguyen, MD Bruce C.V. CampbellBruce C.V. Campbell Correspondence to: Bruce C.V. Campbell, MBBS, PhD, Department of Neurology, Royal Melbourne Hospital, Victoria, Australia. Email E-mail Address: [email protected] https://orcid.org/0000-0003-3632-9433 Departments of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, and the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia (B.C.V.C.). Search for more papers by this author and Thanh N. NguyenThanh N. Nguyen https://orcid.org/0000-0002-2810-1685 Department of Neurology, Radiology, Boston Medical Center, Boston University School of Medicine, MA (T.N.N.). Search for more papers by this author Originally published17 Dec 2021https://doi.org/10.1161/STROKEAHA.121.037039Stroke. 2022;53:264–267Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 17, 2021: Ahead of Print In 2021, interventional stroke therapy has advanced with new data on prehospital triage and treatment, bridging thrombolysis, basilar artery thrombectomy, and imaging selection in the late window.Prehospital, paramedic-led triage of patients with severe stroke syndromes was studied in the RACECAT randomized trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion), situated in Catalonia. Patients often required long-distance transfer (median, 61 [interquartile range, 35–86] minutes), contrasting with modeling studies that indicated benefit of bypass strategies within metropolitan regions. The study was neutral: increased rates of endovascular thrombectomy (EVT), with reduced time to treatment, did not offset increased and faster thrombolysis in the patients who received drip-and-ship treatment. This trial suggests that the drip-and-ship model remains appropriate in rural areas, particularly when primary stroke centers have fast workflow and door-in-door-out times.RACECAT is unlikely to change the preference for paramedic-initiated bypass in metropolitan regions. However, 2 quasi-randomized trials indicated reduced disability with treatment on a mobile stroke unit compared with ambulance transport to the emergency department in ischemic stroke patients deemed eligible for alteplase.1,2 The ≈10% absolute increase in modified Rankin Scale score of 0 to 1 essentially doubles the effect of alteplase observed in emergency department–based trials of thrombolysis <3 hours after stroke onset. In these studies, there was no reduction in time to EVT. However, in geographies with increased primary stroke center distribution in metropolitan areas, the triage of large vessel occlusion to comprehensive centers saved considerable time.3 Given the greater magnitude of benefit per minute saved for EVT, this may enhance the overall benefit of mobile stroke units in some regions and drive expansion of mobile stroke units in developed countries.On arrival in the emergency department, the concept of direct transfer to the angiography suite was explored in the ANGIOCAT randomized trial (Evaluation of Direct Transfer to Angiography Suite vs Computed Tomography Suite in Endovascular Treatment),4 and observational data from Sarraj et al.5 ANGIOCAT demonstrated that omitting conventional computed tomography (CT) imaging on arrival in an endovascular-capable hospital saved time and reduced disability. However, over 70% of patients had been transferred from another hospital where they presumably had CT imaging, increasing the positive predictive value for large vessel occlusion.4 Proceeding direct-to-angiography strategy in patients with a confirmed arterial occlusion or after exclusion of intracerebral hemorrhage is different to taking patients direct from ambulance to angiography. Indeed, there was heterogeneity in the effect of a direct-to-angiography strategy with no signal of benefit in the patients taken directly from the field. Similarly, Sarraj et al5 found that repeat imaging did not improve the safety of treatment and caused delay. Reimaging should be restricted to scenarios when the potential to change management justifies the delay incurred.Whether to give intravenous thrombolytics before thrombectomy when a patient presents directly to a comprehensive stroke center is a key question. The DIRECT-MT (Direct Intraarterial Thrombectomy to Revascularize Acute Ischemic Stroke Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals)6 and DEVT (Direct Endovascular Treatment Versus Standard Bridging Therapy for Patients With Acute Stroke With Large Vessel Occlusion in the Anterior Circulation) trials,7 performed in China, met their prespecified noninferiority margins; the SKIP (Direct Mechanical Thrombectomy in Acute LVO Stroke),8 MR-CLEAN No-IV,9 SWIFT DIRECT (Solitaire With the Intention for Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire Stent-Retriever Thrombectomy in Acute Anterior Circulation Stroke), and DIRECT-SAFE (A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval Versus Standard Bridging Thrombolysis With Endovascular Clot Retrieval) trials did not.10 A study-level meta-analysis found that the CI for the overall risk difference met a 10% noninferiority margin but not a more clinically relevant 5% margin.11 Individual patient-level data meta-analyses are pending and may indicate subgroups for whom direct thrombectomy is beneficial. Overall, trends favored bridging therapy in functional outcomes. There was no excess in mortality, despite a numeric increase in symptomatic intracerebral hemorrhage. Reperfusion at the conclusion of the procedure was increased with bridging therapy. This counters the argument that thrombolytics decrease the quality of final reperfusion due to clot migration. It is also important to recognize that the noninferiority margins in these trials were generous and that the trial workflow delayed administration of thrombolysis due to the need to wait for the EVT decision before consenting, randomizing, and eventually administering alteplase to patients in the bridging arm. This reduced the time available for thrombolytics to have an effect and, in cases when the alteplase infusion was ceased at arterial puncture, reduced the total dose given. Except for a few patients in DIRECT-SAFE who received tenecteplase, alteplase was the comparator. Previous studies indicated not only noninferior but superior reperfusion and functional outcomes with tenecteplase versus alteplase in these patients with large vessel occlusion,12,13 and trials are ongoing (ATTEST-2 [Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis], https://www.clinicaltrials.gov, unique identifier: NCT02814409; AcT [Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke], https://www.clinicaltrials.gov, unique identifier: NCT03889249; TIMELESS [Thrombolysis in Imaging-Eligible, Late-Window Patients to Assess the Efficacy and Safety of Tenecteplase], https://www.clinicaltrials.gov, unique identifier: NCT03785678; ETERNAL [Extending the Time Window for Tenecteplase by Effective Reperfusion in Patients With Large Vessel Occlusion], https://www.clinicaltrials.gov, unique identifier: NCT04454788).Thrombectomy between 6 to 24 hours after stroke onset is well established in guidelines and practice using perfusion or clinical-core mismatch selection. The AURORA (Analysis of Pooled Data from Randomized Studies of Thrombectomy More Than 6 Hours After Last Known Well) collaboration pooled individual patient data from trials of thrombectomy >6 hours after stroke onset.14,15 Both mismatch selection approaches identified patients who benefited from thrombectomy in the late time window. However, perfusion mismatch identified more patients, and there was no heterogeneity in effect between 6 to 16 and 16 to 24 hours, justifying a simplified perfusion mismatch approach throughout the 6- to 24-hour time window. Observational data have also suggested benefit >24 hours in these patients.16 The CLEAR multicenter cohort study (CT for Late Endovascular Reperfusion) evaluated patients with proximal anterior circulation large vessel occlusion treated with EVT in the 6- to 24-hour time window, selected by noncontrast CT, CT perfusion, or magnetic resonance imaging.17 Patients selected by noncontrast CT (median ASPECTS score, 8 [interquartile range, 7–9]) versus advanced imaging had similar ordinal modified Rankin Scale shift and functional independence (modified Rankin Scale score, 0–2) outcomes at 90 days. These findings, if supported by randomized trials (eg, MR CLEAN Late [Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands for Late Arrivals], ISRCTN19922220; RESILIENTExt [Randomization of Endovascular Treatment With Stent-Retriever and/or Thromboaspiration Versus Best Medical Therapy in Acute Ischemic Stroke due to Large Vessel Occlusion Trial Extend], https://www.clinicaltrials.gov, unique identifier: NCT04256096), may broaden the indication for treating patients in the extended time window with a noncontrast CT paradigm.Equipoise to randomize patients with basilar artery occlusion has challenged trialists.18 The BEST trial (Basilar Artery Occlusion Endovascular Intervention Versus Standard Medical Treatment) was prematurely terminated due to substantial crossover from control to thrombectomy.19 The intention-to-treat analysis was neutral, but there was 23% absolute improvement in the modified Rankin Scale score of 0 to 3 in the as-treated analysis. The BASICS trial (Basilar Artery International Cooperation Study) completed enrollment of 300 patients over 8 years. The protocol was modified to include patients with a National Institutes of Health Stroke Scale score <10 to facilitate recruitment. Overall results were neutral, but the subgroup of patients meeting the original trial eligibility of the National Institutes of Health Stroke Scale score ≥10 had benefit,20 supported by pooled analysis with BEST.21 Another randomized trial is ongoing in China (BAOCHE [Basilar Artery Occlusion Chinese Endovascular Trial], https://www.clinicaltrials.gov, unique identifier: NCT04751708). Clinicians will likely continue to perform thrombectomy for patients with basilar artery occlusion, despite the equivocal randomized data, based on the dire natural history and the challenges of achieving unbiased randomization into clinical trials.Mechanical thrombectomy techniques continue to advance. ASTER2 (Combined Use of Contact Aspiration and the Stent Retriever Technique Versus Stent Retriever Alone for Recanalisation in Acute Cerebral Infarction) showed no improvement in the rate of expanded Treatment in Cerebral Ischemia score 2c/3 reperfusion in patients who underwent stent retriever combined with aspiration compared with stent retriever alone as initial thrombectomy strategy.22 In the single-arm TIGER study (Treatment With Intent to Generate Endovascular Reperfusion) of a stent retriever with adjustable radial force, successful reperfusion (Treatment in Cerebral Ischemia score of 2b/3) within 3 passes was achieved in 84.6% of patients. First-pass reperfusion occurred in 41.4%,23 comparing favorably to 25% in the NASA24 registry (North American Solitaire Stent Retriever Acute Stroke Registry). Observational data suggested benefit of EVT in patients with distal vessel occlusion,25 posterior cerebral artery,26–28 and fetal posterior cerebral artery occlusion29 but require cautious interpretation pending randomized trials (DISTAL [Endovascular Therapy Plus Best Medical Treatment (BMT) Versus BMT Alone for Medium Vessel Occlusion Stroke], https://www.clinicaltrials.gov, unique identifier: NCT05029414; ESCAPE MeVO [Endovascular Treatment to Improve Outcomes for Medium Vessel Occlusions], https://www.clinicaltrials.gov, unique identifier: NCT05151172; DISCOUNT [Evaluation of Mechanical Thrombectomy in Acute Ischemic Stroke Related to a Distal Arterial Occlusion], https://www.clinicaltrials.gov, unique identifier: NCT05030142).Article InformationSources of FundingNone.Disclosures Dr Nguyen reports research support from Medtronic and the Society of Vascular and Interventional Neurology. Dr Campbell reports no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Sources of Funding and Disclosures, see page 266.Correspondence to: Bruce C.V. Campbell, MBBS, PhD, Department of Neurology, Royal Melbourne Hospital, Victoria, Australia. Email bruce.[email protected]org.auReferences1. Grotta JC, Yamal JM, Parker SA, Rajan SS, Gonzales NR, Jones WJ, Alexandrov AW, Navi BB, Nour M, Spokoyny Iet al. Prospective, multicenter, controlled trial of mobile stroke units.N Engl J Med. 2021; 385:971–981. doi: 10.1056/NEJMoa2103879CrossrefMedlineGoogle Scholar2. 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Direct to angiography suite without stopping for computed tomography imaging for patients with acute stroke: a randomized clinical trial.JAMA Neurol. 2021; 78:1099–1107. doi: 10.1001/jamaneurol.2021.2385CrossrefGoogle Scholar5. Sarraj A, Goyal N, Chen M, Grotta JC, Blackburn S, Requena M, Kamal H, Abraham MG, Elijovich L, Dannenbaum Met al. Direct to angiography vs repeated imaging approaches in transferred patients undergoing endovascular thrombectomy.JAMA Neurol. 2021; 78:916–926. doi: 10.1001/jamaneurol.2021.1707CrossrefMedlineGoogle Scholar6. Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, Peng Y, Han H, Wang J, Wang Set al; DIRECT-MT Investigators.Endovascular thrombectomy with or without intravenous alteplase in acute stroke.N Engl J Med. 2020; 382:1981–1993. doi: 10.1056/NEJMoa2001123CrossrefMedlineGoogle Scholar7. 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Mechanical thrombectomy of the fetal posterior cerebral artery.Stroke Vasc Interv Neurol. 2021. http://dx.doi.org/10.1161/svin.121.000115Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByNguyen T, Klein P, Berberich A, Nagel S, Abdalkader M, Herning A, Chen Y, Huo X, Miao Z, Sheth S, Qureshi M, Siegler J, Sacco S, Strbian D, Fischer U, Yamagami H, Kristoffersen E, Puetz V, Schonewille W, Tsivgoulis G, Drumm B, Banerjee S, Demeestere J, Alemseged F, Sandset E, Arsovska A, Krishnan K, Dhillon P, Corredor A, Rivera R, Sedova P, Mikulik R, Masoud H, Martins S, Nguyen T, Ton M, Liu X, Zhu Y, Li F, Zaidi W, Zedde M, Yaghi S, Miao J, Inoa V, Zhang L, Masiliūnas R, Slade P, Matuja S, Marto J, Michel P, Fiehler J, Thomalla G, Castonguay A, Mokin M, Parsons M, Campbell B, Yavagal D, Dippel D, Goyal M, Zaidat O, Jovin T, Hu W, Nogueira R, Qiu Z, Raymond J and Saposnik G (2022) Late Window Imaging Selection for Endovascular Therapy of Large Vessel Occlusion Stroke: An International Survey, Stroke: Vascular and Interventional Neurology, 3:1, Online publication date: 1-Jan-2023.Drumm B, Banerjee S, Qureshi M, Schonewille W, Klein P, Huo X, Chen Y, Strbian D, Fischer U, Puetz V, Hu W, Ji X, Li C, Alemseged F, Yamagami H, Sacco S, Saposnik G, Michel P, Kristoffersen E, Sedova P, Mikulik R, Siegler J, Meinel T, Aguiar de Sousa D, Lobotesis K, Roi D, Demeestere J, Asif K, Martins S, Abdalkader M, Goyal M, Nguyen T, Ton M, Zhu Y, Liu X, Qiu Z, Miao Z, Caroff J, Romoli M, Diana F, Thomalla G, Nagel S, Sandset E, Campbell B, Jovin T, Nogueira R, Raymond J and Nguyen T (2022) Current Opinions on Optimal Management of Basilar Artery Occlusion: After the BEST of BASICS Survey, Stroke: Vascular and Interventional Neurology, 2:5, Online publication date: 1-Sep-2022. Kaiser D, Abdalkader M, Berberich A, Sporns P and Nguyen T (2022) Acute shortage of iodinated contrast media: implications and guidance for neurovascular imaging and intervention, Neuroradiology, 10.1007/s00234-022-02999-6 Berberich A, Finitsis S, Strambo D, Michel P, Herweh C, Meyer L, Hanning U, Strbian D, Abdalkader M, Nogueira R, Puetz V, Kaiser D, Olive‐Gadea M, Ribo M, Fragata I, Marto J, Romoli M, Ringleb P, Nguyen T and Nagel S (2022) Endovascular therapy versus no endovascular therapy in patients receiving best medical management for acute isolated occlusion of the posterior cerebral artery: A systematic review and meta‐analysis , European Journal of Neurology, 10.1111/ene.15410 Mai D, Dao X, Luong N, Nguyen T, Nguyen H and Nguyen T (2022) Current State of Stroke Care in Vietnam, Stroke: Vascular and Interventional Neurology, 2:2, Online publication date: 1-Mar-2022.Broderick J and Hill M (2022) Advances in Stroke: Treatments-Acute, Stroke, 53:3, (999-1003), Online publication date: 1-Mar-2022. January 2022Vol 53, Issue 1 Advertisement Article InformationMetrics © 2021 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.121.037039PMID: 34915739 Originally publishedDecember 17, 2021 Keywordsischemic strokereperfusionthrombolytic therapyworkflowthrombectomyPDF download Advertisement" @default.
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