During the last 5-7 years, tremendous progress was achieved in the reperfusion treatment of acute ischaemic stroke during its first few hours from symptom onset. This review summarizes the latest evidence from randomized clinical trials and prospective registries with a focus on endovascular treatment using stent retrievers, aspiration catheters, thrombolytics, and (in selected patients) carotid stenting. Novel approaches in prehospital (mobile interventional stroke teams) and early hospital (direct transfer to angiography) management are described, and future perspectives ('all-in-one' laboratories with angiography and computed tomography integrated) are discussed. There is reasonable chance for patients with moderate-to-severe acute ischaemic stroke to survive without permanent sequelae when the large-vessel occlusion is removed by means of modern pharmaco-mechanic approach. Catheter thrombectomy is now the golden standard of acute stroke treatment. The role of cardiologists in stroke is expanding from diagnostic help (to reveal the cause of stroke) to acute therapy in those regions where such up-to-date Class I. A treatment is not yet available.

Cardiocenter Charles University and University Hospital Kralovske Vinohrady Ruska 87 Prague 10 Czech Republic

Department of Neurology at the 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady Ruska 87 Prague 10 Czech Republic

Department of Neurosurgery Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo NY USA

Komentář v

Eur Heart J. 2023 Apr 7;44(14):1193-1196. doi: 10.1093/eurheartj/ehad198. PubMed

Zobrazit více v PubMed

Wagner  A, Schebesch  KM, Isenmann  S, Steinbrecher  A, Kapapa  T, Zeman  F, et al.  Interdisciplinary decision making in hemorrhagic stroke based on CT imaging—differences between neurologists and neurosurgeons regarding estimation of patients’ symptoms, Glasgow Coma Scale, and National Institutes of Health Stroke Scale. Front Neurol  2019;10:997. 10.3389/fneur.2019.00997 PubMed DOI PMC

Manners  J, Khandker  N, Barron  A, Aziz  Y, Desai  SM, Morrow  B, et al.  An interdisciplinary approach to inhospital stroke improves stroke detection and treatment time. J Neurointerv Surg  2019;11:1080–1084. 10.1136/neurintsurg-2019-014890 PubMed DOI

Widimsky  P, Doehner  W, Diener  HC, Van Gelder  IC, Halliday  A, Mazighi  M, et al.  The role of cardiologists in stroke prevention and treatment: position paper of the European Society of Cardiology Council on Stroke. Eur Heart J  2018;39:1567–1573. 10.1093/eurheartj/ehx478 PubMed DOI

Lip  GYH, Lane  DA, Lenarczyk  R, Boriani  G, Doehner  W, Benjamin  LA, et al.  Integrated care for optimizing the management of stroke and associated heart disease: a position paper of the European Society of Cardiology Council on Stroke. Eur Heart J  2022;43:2442–2460. 10.1093/eurheartj/ehac245 PubMed DOI PMC

Nardai  S, Lanzer  P, Abelson  M, Baumbach  A, Doehner  W, Hopkins  LN, et al.  Interdisciplinary management of acute ischaemic stroke: current evidence training requirements for endovascular stroke treatment: position paper from the ESC Council on Stroke and the European Association for Percutaneous Cardiovascular Interventions with the support of the European Board of Neurointervention. Eur Heart J  2021;42:298–307. 10.1093/eurheartj/ehaa833 PubMed DOI

Nogueira  RG, Jadhav  AP, Haussen  DC, Bonafe  A, Budzik  RF, Bhuva  P, et al.  Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med  2018;378:11–21. 10.1056/NEJMoa1706442 PubMed DOI

Saver  JL, Goyal  M, van der Lugt  A, Menon  BK, Majoie  CB, Dippel  DW, et al.  Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA  2016;316:1279–1288. 10.1001/jama.2016.13647 PubMed DOI

Cash  RE, Boggs  KM, Richards  CT, Camargo  CA  Jr, Zachrison  KS. Emergency medical service time intervals for patients with suspected stroke in the United States. Stroke  2022;53:e75–e78. 10.1161/STROKEAHA.121.037509 PubMed DOI

Choi  PMC, Tsoi  AH, Pope  AL, Leung  S, Frost  T, Loh  PS, et al.  Door-in-door-out time of 60 minutes for stroke with emergent large vessel occlusion at a primary stroke center. Stroke  2019;50:2829–2834. 10.1161/STROKEAHA.119.025838 PubMed DOI

McTaggart  RA, Moldovan  K, Oliver  LA, Dibiasio  EL, Baird  GL, Hemendinger  ML, et al.  Door-in-door-out time at primary stroke centers may predict outcome for emergent large vessel occlusion patients. Stroke  2018;49:2969–2974. 10.1161/STROKEAHA.118.021936 PubMed DOI

Morey  JR, Zhang  X, Marayati  NF, Matsoukas  S, Fiano  E, Oxley  T, et al.  Mobile interventional stroke teams improve outcomes in the early time window for large vessel occlusion stroke. Stroke  2021;52:e527–e530. 10.1161/STROKEAHA.121.034222 PubMed DOI

Widimsky  P, Asil  T, Abelson  M, Koznar  B, Tasal  A, Roos  J, et al.  Direct catheter-based thrombectomy for acute ischemic stroke: outcomes of consecutive patients treated in interventional cardiology centers in close cooperation with neurologists. J. Am Coll Cardiol  2015;66:487–488. 10.1016/j.jacc.2015.04.076 PubMed DOI

Requena  M, Ren  Z, Ribo  M. Direct transfer to angiosuite in acute stroke: why, when, and how?  Neurology  2021;97:S34–S41. 10.1212/WNL.0000000000012799 PubMed DOI

Requena  M, Olivé-Gadea  M, Muchada  M, Hernández  D, Rubiera  M, Boned  S, et al.  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. 10.1001/jamaneurol.2021.2385 PubMed DOI PMC

Jovin  TG, Nogueira  RG, Lansberg  MG, Demchuk  AM, Martins  SO, Mocco  J, et al.  Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis. Lancet  2022;399:249–258. 10.1016/S0140-6736(21)01341-6 PubMed DOI

Nogueira  RG, Haussen  DC, Liebeskind  DS, Jovin  TG, Gupta  R, Saver  JL, et al.  Clinical effectiveness of endovascular stroke treatment in the early and extended time windows. Int J Stroke  2022;17:389–399. 10.1177/17474930211005740 PubMed DOI

Mori  E, Yoneda  Y, Tabuchi  M, Yoshida  T, Ohkawa  S, Ohsumi  Y, et al.  Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke. Neurology  1992;42:976–982. 10.1212/WNL.42.5.976 PubMed DOI

The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group . Tissue plasminogen activator for acute ischemic stroke. N Engl J Med  1995;333:1581–1587. PubMed

Lees  KR, Bluhmki  E, von Kummer  R, Brott  TG, Toni  D, Grotta  JC, et al.  Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet  2010;375:1695–1703. 10.1016/S0140-6736(10)60491-6 PubMed DOI

Ma  H, Campbell  BCV, Parsons  MW, Churilov  L, Levi  CR, Hsu  C, et al.  Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med  2019;380:1795–1803. 10.1056/NEJMoa1813046 PubMed DOI

Lim  JC, Churilov  L, Bivard  A, Ma  H, Dowling  RJ, Campbell  BCV, et al.  Does intravenous thrombolysis within 4.5 to 9 hours increase clot migration leading to endovascular inaccessibility?  Stroke  2021;52:1083–1086. 10.1161/STROKEAHA.120.030661 PubMed DOI

Reiff  T, Barthel  O, Ringleb  PA, Pfaff  J, Mundiyanapurath  S. Safety of mechanical thrombectomy with combined intravenous thrombolysis in stroke treatment 4.5 to 9 hours from symptom onset. J Stroke Cerebrovasc Dis  2020;29:105204. 10.1016/j.jstrokecerebrovasdis.2020.105204 PubMed DOI

Furlan  A, Higashida  R, Wechsler  L, Gent  M, Rowley  H, Kase  C, et al.  Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in acute cerebral thromboembolism. JAMA  1999;282:2003–2011. 10.1001/jama.282.21.2003 PubMed DOI

Khatri  P, Hill  MD, Palesch  YY, Spilker  J, Jauch  EC, Carrozzella  JA, et al.  Methodology of the interventional management of stroke III trial. Int J Stroke  2008;3:130–137. 10.1111/j.1747-4949.2008.00151.x PubMed DOI PMC

Renú  A, Millán  M, San Román  L, Blasco  J, Martí-Fŕbregas  J, Terceńo  M, et al.  Effect of intra-arterial alteplase vs placebo following successful thrombectomy on functional outcomes in patients with large vessel occlusion acute ischemic stroke. The CHOICE randomized clinical trial. JAMA  2022;327:826–835. 10.1001/jama.2022.1645 PubMed DOI PMC

Zhou  Y, Zhang  L, Ospel  J, Goyal  M, McDonough  R, Xing  P, et al.  Association of intravenous alteplase, early reperfusion, and clinical outcome in patients with large vessel occlusion stroke: post hoc analysis of the randomized DIRECT-MT trial. Stroke  2022;53:1828–1836. 10.1161/STROKEAHA.121.037061 PubMed DOI

LeCouffe  NE, Kappelhof  M, Treurniet  KM, Rinkel  LA, Bruggeman  AE, Berkhemer  OA, et al.  A randomized trial of intravenous alteplase before endovascular treatment for stroke. N Engl J Med  2021;385:1833–1844. 10.1056/NEJMoa2107727 PubMed DOI

Suzuki  K, Matsumaru  Y, Takeuchi  M, Morimoto  M, Kanazawa  R, et al.  Effect of mechanical thrombectomy without vs with intravenous thrombolysis on functional outcome among patients with acute ischemic stroke. The SKIP randomized clinical trial. JAMA  2021;325:244–253. 10.1001/jama.2020.23522 PubMed DOI PMC

Campbell  BCV, Mitchell  PJ, Churilov  L, Yassi  N, Kleinig  TJ, Dowling  RJ, et al.  Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med  2018;378:1573–1582. 10.1056/NEJMoa1716405 PubMed DOI

Berkhemer  OA, Fransen  PSS, Beumer  D, van den Berg  LA, Lingsma  HF, Yoo  AJ, et al.  A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372:11–20. 10.1056/NEJMoa1411587 PubMed DOI

Campbell  BCV, Mitchell  PJ, Kleinig  TJ, Dewey  HM, Churilov  L, Yassi  N, et al.  Endovascular therapy for ischemic stroke with per- fusion-imaging selection. N Engl J Med  2015;372:1009–1018. 10.1056/NEJMoa1414792 PubMed DOI

Goyal  M, Demchuk  AM, Menon  BK, Eesa  M, Rempel  JL, Thorn- ton  J, et al.  Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med  2015;372:1019–1030. 10.1056/NEJMoa1414905 PubMed DOI

Jovin  TG, Chamorro  A, Cobo  E, de Miquel  MA, Molina  CA, Rovira  A, et al.  Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med  2015;372:2296–2306. 10.1056/NEJMoa1503780 PubMed DOI

Saver  JL, Goyal  M, Bonafe  A, Diener  H-C, Levy  EI, Pereira  VM, et al.  Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med  2015;372:2285–2295. 10.1056/NEJMoa1415061 PubMed DOI

Goyal  M, Menon  BK, van Zwam  WH, Dippel  DWJ, Mitchell  PJ, Demchuk  AM, et al.  Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet  2016;387:1723–1731. 10.1016/S0140-6736(16)00163-X PubMed DOI

Albers  GW, Marks  MP, Kemp  S, Christensen  S, Tsai  JP, Ortega-Gutierrez  S, et al.  Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med  2018;378:708–718. 10.1056/NEJMoa1713973 PubMed DOI PMC

Sarraj  A, Hassan  AE, Savitz  S, Sitton  C, Grotta  J, Chen  P, et al.  Outcomes of endovascular thrombectomy vs medical management alone in patients with large ischemic cores: a secondary analysis of the optimizing patient’s selection for endovascular treatment in acute ischemic stroke (SELECT) study. JAMA Neurol  2019;76:1147–1156. 10.1001/jamaneurol.2019.2109 PubMed DOI PMC

Yoshimura  S, Sakai  N, Yamagami  H, Uchida  K, Beppu  M, Toyoda  K, et al.  Endovascular therapy for acute stroke with a large ischemic region. N Engl J Med  2022;386:1303–1313. 10.1056/NEJMoa2118191 PubMed DOI

Perianen  PP, Yan  B. Are we ready to offer endovascular thrombectomy to all patients with large ischemic core?  Front Neurol  2022;13:893975. 10.3389/fneur.2022.893975 PubMed DOI PMC

Sarraj  A, Hassan  A, Savitz  SI, Grotta  JC, Cai  C, Parsha  KN, et al.  Endovascular thrombectomy for mild strokes: how low should we go?  Stroke  2018;49:2398–2405. 10.1161/STROKEAHA.118.022114 PubMed DOI PMC

Goyal  N, Tsivgoulis  G, Malhotra  K, Ishfaq  MF, Pandhi  A, Frohler  MT, et al.  Medical management vs mechanical thrombectomy for mild strokes: an international multicenter study and systematic review and meta-analysis. JAMA Neurol  2020;77:16–24. 10.1001/jamaneurol.2019.3112 PubMed DOI PMC

Seners  P, Ben Hassen  W, Lapergue  B, Arquizan  C, Heldner  MR, Henon  H, et al.  Prediction of early neurological deterioration in individuals with Minor stroke and large vessel occlusion intended for intravenous thrombolysis alone. JAMA Neurol  2021;78:321–328. 10.1001/jamaneurol.2020.4557 PubMed DOI PMC

Zaidat  OO, Mueller-Kronast  NH, Hassan  AE, Haussen  DC, Jadhav  AP, Froehler  MT, et al.  Impact of balloon guide catheter use on clinical and angiographic outcomes in the STRATIS stroke thrombectomy registry. Stroke  2019;50:697–704. 10.1161/STROKEAHA.118.021126 PubMed DOI

Brinjikji  W, Starke  RM, Murad  MH, Fiorella  D, Pereira  VM, Goyal  M, et al.  Impact of balloon guide catheter on technical and clinical outcomes: a systematic review and meta-analysis. J Neurointerv Surg  2018;10:335–339. 10.1136/neurintsurg-2017-013179 PubMed DOI

Lapergue  B, Blanc  R, Gory  B, Labreuche  J, Duhamel  A, Marnat  G, et al.  Effect of endovascular contact aspiration vs stent retriever on revascularization in patients with acute ischemic stroke and large vessel occlusion: the aster randomized clinical trial. JAMA  2017;318:443–452. 10.1001/jama.2017.9644 PubMed DOI PMC

Nogueira  RG, Frei  D, Kirmani  JF, Zaidat  O, Lopes  D, Turk  AS  III, et al.  Safety and efficacy of a:3. -dimensional stent retriever with aspiration-based thrombectomy vs aspiration-based thrombectomy alone in acute ischemic stroke intervention: a randomized clinical trial. JAMA Neurol  2018;75:304–311. 10.1001/jamaneurol.2017.3967 PubMed DOI PMC

Turk  AS  III, Siddiqui  A, Fifi  JT, De Leacy  RA, Fiorella  DJ, Gu  E, , et al.  Aspiration thrombectomy versus stent retriever thrombectomy as first-line approach for large vessel occlusion (compass): a multicentre, randomised, open label, blinded outcome, non-inferiority trial. Lancet  2019;393:998–1008. 10.1016/S0140-6736(19)30297-1 PubMed DOI

Mohammaden  MH, Haussen  DC, Perry da Camara  C, Pisani  L, Olive Gadea  M, Al-Bayati  AR, et al.  Hyperdense vessel sign as a potential guide for the choice of stent retriever versus contact aspiration as first-line thrombectomy strategy. J Neurointerv Surg  2021;13:599–604. 10.1136/neurintsurg-2020-016005 PubMed DOI

Bourcier  R, Mazighi  M, Labreuche  J, Fahed  R, Blanc  R, Gory  B, et al.  Susceptibility vessel sign in the aster trial: higher recanalization rate and more favourable clinical out- come after first line stent retriever compared to contact aspiration. J Stroke  2018;20:268–276. 10.5853/jos.2018.00192 PubMed DOI PMC

Langezaal  LCM, van der Hoeven  EJRJ, Mont’Alverne  FJA, de Carvalho  JJF, Lima  FO, Dippel  DWJ, et al.  Endovascular therapy for stroke due to basilar-artery occlusion. N Engl J Med  2021;384:1910–1920. 10.1056/NEJMoa2030297 PubMed DOI

Liu  X, Dai  Q, Ye  R, Zi  W, Liu  Y, Wang  H, et al.  Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial. Lancet Neurol  2020;19:115–122. 10.1016/S1474-4422(19)30395-3 PubMed DOI

Tao  C, Nogueira  RG, Zhu  Y, Sun  J, Han  H, Yuan  G, et al.  Trial of endovascular treatment of acute basilar-artery occlusion. N Engl J Med  2022; 387:1361–1372. 10.1056/NEJMoa2206317 PubMed DOI

Da Ros  V, Scaggiante  J, Pitocchi  F, Sallustio  F, Lattanzi  S, Umana  GE, et al.  Mechanical thrombectomy in acute ischemic stroke with tandem occlusions: impact of extracranial carotid lesion etiology on endovascular management and outcome. Neurosurg Focus  2021;51:E6. 10.3171/2021.4.FOCUS21111 PubMed DOI

Haussen  DC, Turjman  F, Piotin  M, Labreuche  J, Steglich-Arnholm  H, Holtmannspötter  M, et al.  Head or neck first? Speed and rates of reperfusion in thrombectomy for tandem large vessel occlusion strokes. Interv Neurol  2020; 8:92–100. 10.1159/000496292 PubMed DOI PMC

Zinkstok  SM, Roos  YB. Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet  2012;380:731–737. 10.1016/S0140-6736(12)60949-0 PubMed DOI

Papanagiotou  P, Haussen  DC, Turjman  F, Labreuche  J, Piotin  M, Kastrup  A, et al.  Carotid stenting with antithrombotic agents and intracranial thrombectomy leads to the highest recanalization rate in patients with acute stroke with tandem lesions. JACC Cardiovasc Interv  2018;11:1290–1299. 10.1016/j.jcin.2018.05.036 PubMed DOI

Gory  B, Haussen  DC, Piotin  M, Steglich-Arnholm  H, Holtmannspötter  M, Labreuche  J, et al.  Impact of intravenous thrombolysis and emergent carotid stenting on reperfusion and clinical outcomes in patients with acute stroke with tandem lesion treated with thrombectomy: a collaborative pooled analysis. Eur J Neurol  2018;25:1115–1120. 10.1111/ene.13633 PubMed DOI

Sadeh-Gonik  U, Tau  N, Friehmann  T, Bracard  S, Anxionnat  R, Derelle  AL, et al.  Thrombectomy outcomes for acute stroke patients with anterior circulation tandem lesions: a clinical registry and an update of a systematic review with meta-analysis. Eur J Neurol  2018;25:693–700. 10.1111/ene.13577 PubMed DOI

Stampfl  S, Ringleb  PA, Möhlenbruch  M, Hametner  C, Herweh  C, Pham  M, et al.  Emergency cervical internal carotid artery stenting in combination with intracranial thrombectomy in acute stroke. Am J Neuroradiol  2014;35:741–746. 10.3174/ajnr.A3763 PubMed DOI PMC

Menon  BK, Hill  MD, Davalos  A, Roos  YBWEM, Campbell  BCV, Dippel  DWJ, et al.  Efficacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES collaboration. J Neurointerv Surg  2019;11:1065–1069. 10.1136/neurintsurg-2018-014678 PubMed DOI

Grossberg  JA, Rebello  LC, Haussen  DC, Bouslama  M, Bowen  M, Barreira  CM, et al.  Beyond large vessel occlusion strokes: distal occlusion thrombectomy. Stroke  2018;49:1662–1668. 10.1161/STROKEAHA.118.020567 PubMed DOI

Sandercock  PA, Counsell  C, Kane  EJ. Anticoagulants for acute ischaemic stroke. Cochrane Database Syst Rev. 2015;2015(3):CD000024. 10.1002/14651858.CD000024.pub4 PubMed DOI PMC

Yang  M, Huo  X, Gao  F, Wang  A, Ma  N, Liebeskind  DS, et al.  Safety and efficacy of heparinization during mechanical thrombectomy in acute ischemic stroke. Front Neurol  2019;10:299. 10.3389/fneur.2019.00299 PubMed DOI PMC

Chalos  V, van de Graaf  RA, Roozenbeek  B, van Es  ACGM, den Hertog  HM, Staals J, et al.  Multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke. The effect of periprocedural medication: acetylsalicylic acid, unfractionated heparin, both, or neither (MR CLEAN-MED). Rationale and study design. Trials  2020;21:644. 10.1186/s13063-020-04514-9 PubMed DOI PMC

Simonsen  CZ, Yoo  AJ, Sørensen  LH, Juul  N, Johnsen  SP, Andersen  G, et al.  Effect of general anesthesia and conscious sedation during endovascular therapy on infarct growth and clinical outcomes in acute ischemic stroke. JAMA Neurol  2018;75:470–477. 10.1001/jamaneurol.2017.4474 PubMed DOI PMC

Cappellari  M, Pracucci  G, Forlivesi  S, Saia  V, Nappini  S, Nencini  P, et al.  General anesthesia versus conscious sedation and local anesthesia during thrombectomy for acute ischemic stroke. Stroke  2020;51:2036–2044. 10.1161/STROKEAHA.120.028963 PubMed DOI

Matusevicius  M, Cooray  C, Bottai  M, Mazya  M, Tsivgoulis  G, Nunes  AP, et al.  Blood pressure after endovascular thrombectomy: modelling for outcomes based on recanalization status. Stroke  2020;51:519–525. 10.1161/STROKEAHA.119.026914 PubMed DOI

Bath  PM, Song  L, Silva  GS, Mistry  E, Petersen  N, Tsivgoulis  G, et al.  Blood pressure management for ischemic stroke in the first 24 hours. Stroke  2022;53:1074–1084. 10.1161/STROKEAHA.121.036143 PubMed DOI PMC

Sun  D, Huo  X, Raynald  JB, Tong  X, Ma  G, et al.  Predictors of symptomatic intracranial hemorrhage after endovascular treatment for acute large vessel occlusion: data from ANGEL-ACT registry. J Thromb Thrombolysis  2022;54:558–565. 10.1007/s11239-022-02688-4 PubMed DOI

Neutrophil Extracellular Traps and Thrombolysis Resistance: New Insights for Targeting Therapies

The importance of interdisciplinary research