Akuttherapie des ischämischen Schlaganfalls – Rekanalisierende Therapie^[*]

Zusammenfassung

Hintergrund: Ziel dieses Manuskripts ist ein Update der DGN-Leitlinie zu rekanalisierenden Therapien bei Patienten mit akutem Hirninfarkt, was sowohl die systemische Thrombolyse als auch die mechanische Rekanalisation umfasst. Dies ist Teil der Gesamtüberarbeitung der Leitlinie „Akuttherapie des Hirninfarkte“ (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V., AWMF-Register Nr. 030-046), wurde aber wegen der Relevanz vorab erstellt.

Methodik: Dieses fokussierte Update nimmt Stellung zu den beiden Fragen (1) „Welche Patienten mit akutem Hirninfarkt sollen mit einer systemischen Thrombolyse behandelt werden?“ und (2) „Welche Schlaganfallpatienten mit akutem Hirninfarkt sollten mit einer mechanischen Thrombektomie behandelt werden?“. Es ist nicht vorgesehen eine vollständige systematische Literaturanalyse zu erstellen, weswegen eine Leitlinie auf dem S2k-Niveau nach den Standards der AWMF erstellt wurde. Sechs nominierte Mitglieder der Deutschen Gesellschaft für Neurologie (DGN), der Deutschen Schlaganfallgesellschaft (DSG) und der Deutschen Gesellschaft für Neuroradiologie (DGNR) waren an der Formulierung der Leitlinie beteiligt. Die Vorstände der Fachgesellschaften stimmten der Leitlinie zu. Die Regeln der AWMF und der DGN zum Umgang mit potenziellen Interessenkonflikten wurden während des Konsensprozesses gewahrt.

Ergebnis: Es werden konsensusbasierte Leitlinienempfehlungen zur Selektion von Patienten für die systemische Thrombolyse und die mechanische Rekanalisation vorgestellt, außerdem auch zur Durchführung der Prozeduren.

Schlussfolgerung: Die Empfehlungen dieser Leitlinie können Unsicherheiten bezüglich rekanalisierender Therapiemöglichkeiten bei akuten Schlaganfallpatienten reduzieren und insbes. zur Verbreitung effektiver und sicherer endovaskulärer Techniken beitragen.

Abstract

Purpose: The aim was to provide an update of the current guideline recommendations of the German Neurological Society (DGN) for recanalisation therapy of acute ischemic stroke focusing on systemic thrombolysis and mechanical thrombectomy. This document is part of the update of the entire guideline for acute stroke treatment (AWMF-No 030-046). It was prepared in advance because of major recent developments in this area.

Methods: This update focuses on the two questions: (1) “Which patients with acute ischemic stroke should be treated with systemic thrombolysis?” (2) “Which patients with acute ischemic stroke should be treated with thrombectomy?” It is not intended to provide a complete literature review. The guideline was prepared at an S2k-level according to the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V., AWMF) standards. Accordingly, it does not include a formalized, comprehensive literature review. Six nominated members of the German Neurology Society, the German Stroke Society and the German Society of Neuroradiology, respectively, were involved in the update. The executive committees of these societies approved the guideline. Adherence to the AWMF and the DGN conflict of interest policy was assured throughout the consensus process.

Results: Consensus-based guidelines are presented for the selection of patients with acute ischemic stroke for systemic and endovascular treatment, as well as for the performance of respective procedures.

Conclusion: These guideline recommendations are intended to reduce uncertainties regarding recanalisation therapy in acute ischemic stroke patients, and, in particular, should facilitate implementation of effective and safe endovascular stroke treatment in current clinical practice.

Schlüsselwörter

Leitlinie - akute Schlaganfallbehandlung - systemische Thrombolyse - endovaskuläre Schlaganfalltherapie - mechanische Thrombektomie

Keywords

guideline - acute stroke treatment - systemic thrombolysis - endovascular stroke treatment - mechanical thrombectomy

• Literatur

• 1 [Anonym] Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995; 333: 1581-1587
• 2 Hacke W, Donnan G, Fieschi C et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004; 363: 768-774
• 3 Hacke W, Kaste M, Bluhmki E et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359: 1317-1329
• 4 Lees KR, Bluhmki E, von Kummer R 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
• 5 Emberson J, Lees KR, Lyden P et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014; 384: 1929-1935
• 6 Wahlgren N, Ahmed N, Davalos A et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007; 369: 275-282
• 7 Wahlgren N, Ahmed N, Davalos A et al. Thrombolysis with alteplase 3–4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet 2008; 372: 1303-1309
• 8 Mishra NK, Diener HC, Lyden PD et al. Influence of age on outcome from thrombolysis in acute stroke: a controlled comparison in patients from the Virtual International Stroke Trials Archive (VISTA). Stroke 2010; 41: 2840-2848
• 9 Toni D, Lorenzano S, Agnelli G et al. Intravenous thrombolysis with rt-PA in acute ischemic stroke patients aged older than 80 years in Italy. Cerebrovasc Dis 2008; 25: 129-135
• 10 Rother J, Schellinger PD, Gass A et al. Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke <6 hours. Stroke 2002; 33: 2438-2445
• 11 Schellinger PD, Thomalla G, Fiehler J et al. MRI-based and CT-based thrombolytic therapy in acute stroke within and beyond established time windows: an analysis of 1210 patients. Stroke 2007; 38: 2640-2645
• 12 Mishra NK, Albers GW, Davis SM et al. Mismatch-based delayed thrombolysis: a meta-analysis. Stroke 2010; 41: e25-33
• 13 Smith EE, Abdullah AR, Petkovska I et al. Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke. Stroke 2005; 36: 2497-2499
• 14 Nedeltchev K, Schwegler B, Haefeli T et al. Outcome of stroke with mild or rapidly improving symptoms. Stroke 2007; 38: 2531-2535
• 15 Steffenhagen N, Hill MD, Poppe AY et al. Should you thrombolyse all or any stroke patients with baseline National Institutes of Health stroke scale scores < or = 5?. Cerebrovasc Dis 2009; 28: 201-202
• 16 Shi L, Zhang M, Liu H et al. Safety and outcome of thrombolysis in mild stroke: a meta-analysis. Med Sci Monit 2014; 20: 2117-2124
• 17 Mishra NK, Ahmed N, Davalos A et al. Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and diabetes mellitus. Neurology 2011; 77: 1866-1872
• 18 Alhazzaa M, Sharma M, Blacquiere D et al. Thrombolysis despite recent stroke: a case series. Stroke 2013; 44: 1736-1738
• 19 Karlinski M, Kobayashi A, Mikulik R et al. Intravenous alteplase in ischemic stroke patients not fully adhering to the current drug license in Central and Eastern Europe. Int J Stroke 2012; 7: 615-622
• 20 Breuer L, Blinzler C, Huttner HB et al. Off-label thrombolysis for acute ischemic stroke: rate, clinical outcome and safety are influenced by the definition of 'minor stroke'. Cerebrovasc Dis 2011; 32: 177-185
• 21 Guillan M, Alonso-Canovas A, Garcia-Caldentey J et al. Off-label intravenous thrombolysis in acute stroke. Eur J Neurol 2012; 19: 390-394
• 22 Meretoja A, Putaala J, Tatlisumak T et al. Off-label thrombolysis is not associated with poor outcome in patients with stroke. Stroke 2010; 41: 1450-1458
• 23 De Reuck J, Vanhee F, Van Maele G et al. Magnetic resonance imaging after seizures in patients with an ischemic stroke. Cerebrovasc Dis 2007; 23: 339-343
• 24 Sylaja PN, Dzialowski I, Krol A et al. Role of CT angiography in thrombolysis decision-making for patients with presumed seizure at stroke onset. Stroke 2006; 37: 915-917
• 25 Xian Y, Liang L, Smith EE et al. Risks of intracranial hemorrhage among patients with acute ischemic stroke receiving warfarin and treated with intravenous tissue plasminogen activator. JAMA 2012; 307: 2600-2608
• 26 Mazya MV, Lees KR, Markus R et al. Safety of intravenous thrombolysis for ischemic stroke in patients treated with warfarin. Ann Neurol 2013; 74: 266-274
• 27 Rizos T, Herweh C, Jenetzky E et al. Point-of-care international normalized ratio testing accelerates thrombolysis in patients with acute ischemic stroke using oral anticoagulants. Stroke 2009; 40: 3547-3551
• 28 Cappellari M, Bovi P. Intravenous thrombolysis for stroke in patients taking non-VKA oral anticoagulants: an update. Thromb Haemost 2015; 114: 440-444
• 29 Hankey GJ, Norrving B, Hacke W et al. Management of acute stroke in patients taking novel oral anticoagulants. Int J Stroke 2014; 9: 627-632
• 30 Steiner T, Bohm M, Dichgans M et al. Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban. Clin Res Cardiol 2013; 102: 399-412
• 31 Albers GW, von Kummer R, Truelsen T et al. Safety and efficacy of desmoteplase given 3-9 h after ischaemic stroke in patients with occlusion or high-grade stenosis in major cerebral arteries (DIAS-3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet Neurol 2015; 14: 575-584
• 32 Parsons M, Spratt N, Bivard A et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med 2012; 366: 1099-1107
• 33 Furlan A, Higashida R, Wechsler L 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
• 34 Smith WS, Sung G, Starkman S et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke 2005; 36: 1432-1438
• 35 Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke 2007; 38: 967-973
• 36 Broderick JP, Palesch YY, Demchuk AM et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013; 368: 893-903
• 37 Kidwell CS, Jahan R, Gornbein J et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 2013; 368: 914-923
• 38 Ciccone A, Valvassori L, Nichelatti M et al. Endovascular treatment for acute ischemic stroke. N Engl J Med 2013; 368: 904-913
• 39 Saver JL, Jahan R, Levy EI et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 2012; 380: 1241-1249
• 40 Nogueira RG, Lutsep HL, Gupta R et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet 2012; 380: 1231-1240
• 41 Demchuk AM, Goyal M, Yeatts SD et al. Recanalization and clinical outcome of occlusion sites at baseline CT angiography in the Interventional Management of Stroke III trial. Radiology 2014; 273: 202-210
• 42 Khatri P, Yeatts SD, Mazighi M et al. Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial. Lancet Neurol 2014; 13: 567-574
• 43 Zaidat OO, Yoo AJ, Khatri P et al. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke 2013; 44: 2650-2663
• 44 Tomsick TA, Yeatts SD, Liebeskind DS et al. Endovascular revascularization results in IMS III: intracranial ICA and M1 occlusions. J Neurointerv Surg 2015; 7: 795-802
• 45 Hacke W, Diener HC. Mechanische Thrombektomie bei akutem ischämischem Schlaganfall: Wo stehen wir nach den jüngsten Studienergebnissen?. Der Nervenarzt 2015; 86: 719-724
• 46 Berkhemer OA, Fransen PS, Beumer D et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015; 372: 11-20
• 47 Goyal M, Demchuk AM, Menon BK et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015; 372: 1019-1030
• 48 Campbell BC, Mitchell PJ, Investigators E-I. Endovascular therapy for ischemic stroke. N Engl J Med 2015; 372: 2365-2366
• 49 Straka M, Albers GW, Bammer R. Real-time diffusion-perfusion mismatch analysis in acute stroke. J Magn Reson Imaging 2010; 32: 1024-1037
• 50 Saver JL, Goyal M, Bonafe A et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015; 372: 2285-2295
• 51 Jovin TG, Chamorro A, Cobo E et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015; 372: 2296-2306
• 52 Powers WJ, Derdeyn CP, Biller J et al. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015; 46: 3020-3035
• 53 Fransen PS, Berkhemer OA, Lingsma HF et al. Time to reperfusion and treatment effect for acute ischemic stroke: a randomized clinical trial. JAMA Neurol 2015; 1-7
• 54 Vagal AS, Khatri P, Broderick JP et al. Time to angiographic reperfusion in acute ischemic stroke: decision analysis. Stroke 2014; 45: 3625-3630
• 55 von Kummer R, Broderick JP, Campbell BC et al. The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke 2015; 46: 2981-2986
• 56 Mattle HP, Arnold M, Lindsberg PJ et al. Basilar artery occlusion. Lancet Neurol 2011; 10: 1002-1014
• 57 Schonewille WJ, Wijman CA, Michel P et al. The basilar artery international cooperation study (BASICS). Int J Stroke 2007; 2: 220-223
• 58 Brandt T, von Kummer R, Muller-Kuppers M et al. Thrombolytic therapy of acute basilar artery occlusion. Variables affecting recanalization and outcome. Stroke 1996; 27: 875-881
• 59 Kumar G, Shahripour RB, Alexandrov AV. Recanalization of acute basilar artery occlusion improves outcomes: a meta-analysis. J Neurointerv Surg 2015; 7: 868-874
• 60 Gory B, Eldesouky I, Sivan-Hoffmann R et al. Outcomes of stent retriever thrombectomy in basilar artery occlusion: an observational study and systematic review. J Neurol Neurosurg Psychiatry 2015;
• 61 Mohlenbruch M, Stampfl S, Behrens L et al. Mechanical thrombectomy with stent retrievers in acute basilar artery occlusion. AJNR Am J Neuroradiol 2014; 35: 959-964
• 62 Jumaa MA, Zhang F, Ruiz-Ares G et al. Comparison of safety and clinical and radiographic outcomes in endovascular acute stroke therapy for proximal middle cerebral artery occlusion with intubation and general anesthesia versus the nonintubated state. Stroke 2010; 41: 1180-1184
• 63 Schonenberger S, Mohlenbruch M, Pfaff J et al. Sedation vs. Intubation for Endovascular Stroke TreAtment (SIESTA) – a randomized monocentric trial. Int J Stroke 2015; 10: 969-978