Skip to main content Accessibility help
Hostname: page-component-768ffcd9cc-s8fcc Total loading time: 1.641 Render date: 2022-11-30T06:08:48.840Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "displayNetworkTab": true, "displayNetworkMapGraph": false, "useSa": true } hasContentIssue true

Chapter 6 - Reperfusion of Ischaemic Brain by Intravenous Thrombolysis

from Part III - Acute Treatment of Ischaemic Stroke and Transient Ischaemic Attack

Published online by Cambridge University Press:  15 December 2020

Jeffrey L. Saver
David Geffen School of Medicine, University of Ca
Graeme J. Hankey
University of Western Australia, Perth
Get access


Intravenous thrombolytic therapy (IV) with recombinant tissue-plasminogen activator (alteplase; 0.9 mg/kg over 1h) is beneficial for acute ischaemic stroke patients with potentially disabling neurological deficits, and without contraindications, when started =4.5h of onset. Benefit is time-dependent: among 1000 patients, IVT =3h lessen long-term disability in 178 patients, between 3-4.5h in 66. IVT under 4.5h is associated with an increase in symptomatic haemorrhage, but not an increase in death or severe disability. Based on trial evidence, IVT =3h is strongly endorsed, and between 3-4.5 hours moderately endorsed, by guidelines on 5 continents. Benefit is evident in patients under and over age 80, and in patients with up to moderate, but not extensive (more than 100 cc), early ischaemic changes on initial CT or MRI. IVT is also beneficial for patients =4.5h after onset with substantial salvageable tissue on penumbral CT or MR imaging. Systems of care should be optimized to start IVT =60m, and optimally =30m, after ED arrival. Large-scale trials are needed to further enhance IVT, testing: faster treatment start in mobile stroke units (mobile CT ambulances): fibrinolytic agent and concomitant lytic-enhancing combinations; bridging neuroprotection and collateral enhancement; and the optimal way to combine intravenous thrombolytic therapy and endovascular mechanical thrombectomy.

Stroke Prevention and Treatment
An Evidence-based Approach
, pp. 98 - 126
Publisher: Cambridge University Press
Print publication year: 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Acker, JE III, Pancioli, AM, Crocco, T J, Eckstein, MK, Jauch, EC, Larrabee, H, et al. (2007). Implementation strategies for emergency medical services within stroke systems of care: a policy statement from the American Heart Association/ American Stroke Association Expert Panel on Emergency Medical Services Systems and the Stroke Council. Stroke, 38(11), 3097–115.CrossRefGoogle Scholar
Adeoye, O, Sucharew, H, Khoury, J, Vagal, A, Schmit, PA, Ewing, I, et al. (2015). Combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator in acute ischemic stroke-full dose regimen stroke trial. Stroke, 46(9), 2529–33.CrossRefGoogle ScholarPubMed
Alberts, MJ, Latchaw, RE, Jagoda, A, Wechsler, LR, Crocco, T, George, MG, et al. (2011). Revised and updated recommendations for the establishment of primary stroke centers: a summary statement from the brain attack coalition. Stroke, 42(9), 2651–65.CrossRefGoogle ScholarPubMed
Alexandrov, AV, Kohrmann, M, Soinne, L, Mandava, P, Barreto, AD, Demchuk, AM, et al. (2016). Ultrasound enhanced thrombolysis for ischemic stroke: results of a multi-national phase iii trial – CLOTBUSTER. Paper presented at the European Stroke Organization Conference, Barcelona, Spain.Google Scholar
American College of Emergency Physicians; American Academy of Neurology (2013). Clinical policy: use of intravenous tPA for the management of acute ischemic stroke in the emergency department. Ann Emerg Med, 61, 225–43.Google Scholar
Anderson, CS, Robinson, T, Lindley, RI, Arima, H, Lavados, PM, Lee, TH, et al.; Investigators and Coordinators. (2016). Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke. N Engl J Med, 374(24), 2313–23.CrossRefGoogle ScholarPubMed
Ankolekar, S, Fuller, M, Cross, I, Renton, C, Cox, P, Sprigg, N, et al. (2013). Feasibility of an ambulance-based stroke trial, and safety of glyceryl trinitrate in ultra-acute stroke: the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial (RIGHT, ISRCTN66434824). Stroke, 44(11), 3120–8.CrossRefGoogle ScholarPubMed
Atallah, AM. (2012). Consensus on Diagnosis and Treatment of Acute Ischemic Stroke Council – Argentine Society of Cardiology. Argentine J Cardiol, 80, 389404.Google Scholar
Audebert, HJ, Schenkel, J, Heuschmann, PU, Bogdahn, U, Haberl, RL. (2006). Effects of the implementation of a telemedical stroke network: the Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria, Germany. Lancet Neurol, 5(9), 742–8.CrossRefGoogle Scholar
Barreto, AD, Alexandrov, AV, Lyden, P, Lee, J, Martin-Schild, S, Shen, L, et al. (2012). The argatroban and tissue-type plasminogen activator stroke study: final results of a pilot safety study. Stroke, 43(3), 770–5.CrossRefGoogle ScholarPubMed
Bath, PM, Lees, KR, Schellinger, PD, Altman, H, Bland, M, Hogg, C, et al. (2012). Statistical analysis of the primary outcome in acute stroke trials. Stroke, 43(4), 1171–8.CrossRefGoogle ScholarPubMed
Bendszus, M, Donnan, G, Hacke, W, Molina, C, Leys, D, Ringleb, P, et al.; ECASS-4 Collaborators. (2018). ECASS-4:EXTEND: Extending the Time for Thrombolysis in Emergency Neurological Deficits. Eur Stroke J, 3(Suppl 1), 4 (abstract).Google Scholar
Bivard, A, Huang, X, Levi, CR, Spratt, N, Campbell, BCV, Cheripelli, BK, et al. (2017). Tenecteplase in ischemic stroke offers improved recanalization: analysis of 2 trials. Neurology, 89(1), 62–7.CrossRefGoogle ScholarPubMed
Bluhmki, E, Chamorro, A, Davalos, A, Machnig, T, Sauce, C, Wahlgren, N, et al. (2009). Stroke treatment with alteplase given 3.0–4.5 h after onset of acute ischaemic stroke (ECASS III): additional outcomes and subgroup analysis of a randomised controlled trial. Lancet Neurol, 8(12), 10951102.CrossRefGoogle ScholarPubMed
Bryer, A, Connor, M, Haug, P, Cheyip, B, Staub, H, Tipping, B, et al. (2010). South African guideline for management of ischaemic stroke and transient ischaemic attack 2010: a guideline from the South African Stroke Society (SASS) and the SASS Writing Committee. S Afr Med J, 100(11 Pt 2), 747–78.CrossRefGoogle ScholarPubMed
Campbell, BC; E-IT Investigators. (2018). Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): a multicenter, randomized, controlled trial. Paper presented at the International Stroke Conference, Los Angeles, CA.Google Scholar
Chao, AC, Liu, CK, Chen, CH, Lin, HJ, Liu, CH, Jeng, JS, et al. (2014). Different doses of recombinant tissue-type plasminogen activator for acute stroke in Chinese patients. Stroke, 45(8), 2359–65.CrossRefGoogle ScholarPubMed
Cho, KH, Ko, SB, Kim, SH, Park, HK, Cho, AH, Hong, KS, et al. (2012). Focused update of Korean Clinical Practice Guidelines for the Thrombolysis in Acute Stroke Management. Korean J Stroke, 14, 95105.CrossRefGoogle Scholar
Ciccone, A, Motto, C, Aritzu, E, Piana, A, Candelise, L. (2000). Negative interaction of aspirin and streptokinase in acute ischemic stroke: further analysis of the Multicenter Acute Stroke Trial – Italy. Cerebrovasc Dis, 10(1), 61–4.CrossRefGoogle ScholarPubMed
Daffertshofer, M, Gass, A, Ringleb, P, Sitzer, M, Sliwka, U, Els, T, et al. (2005). Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial. Stroke, 36(7), 1441–6.CrossRefGoogle ScholarPubMed
Davis, SM, Donnan, GA, Parsons, MW, Levi, C, Butcher, KS, Peeters, A, et al. (2008). Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial. Lancet Neurol, 7(4), 299309.CrossRefGoogle ScholarPubMed
DeMers, G, Meurer, WJ, Shih, R, Rosenbaum, S, Vilke, GM. (2012). Tissue plasminogen activator and stroke: review of the literature for the clinician. J Emerg Med 43(6): 11491154.CrossRefGoogle ScholarPubMed
Diener, HC, Foerch, C, Riess, H, Rother, J, Schroth, G, Weber, R. (2013). Treatment of acute ischaemic stroke with thrombolysis or thrombectomy in patients receiving anti-thrombotic treatment. Lancet Neurol, 12(7), 677–88.CrossRefGoogle ScholarPubMed
Emberson, J, Lees, KR, Lyden, P, Blackwell, L, Albers, G, Bluhmki, E, et al. (2014). 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, 384, 1929–35.CrossRefGoogle ScholarPubMed
European Stroke Organization Executive Committee and the ESO Writing Committee. (2008). Guidelines for the Management of Ischaemic Stroke and Transient Ischemic Attack 2008. Accessed July 2013.Google Scholar
Fassbender, K, Grotta, JC, Walter, S, Grunwald, IQ, Ragoschke-Schumm, A, Saver, J. (2017). Mobile stroke units for prehospital thrombolysis, triage, and beyond: benefits and challenges. Lancet Neurol, 16(3), 227–37.CrossRefGoogle ScholarPubMed
Feigin, VL, Norrving, B, Mensah, GA. (2017). Global burden of stroke. Circ Res, 120(3), 439–48.CrossRefGoogle ScholarPubMed
Fischer, U, Kaesmacher, J, Mendes Pereira, V, Chapot, R, Siddiqui, AH, Froehler, MT, et al. (2017). Direct mechanical thrombectomy versus combined intravenous and mechanical thrombectomy in large-artery anterior circulation stroke: a topical review. Stroke, 48(10), 2912–18.CrossRefGoogle ScholarPubMed
Fisher, M, Saver, JL. (2015). Future directions of acute ischaemic stroke therapy. Lancet Neurol, 14(7), 758–67.CrossRefGoogle ScholarPubMed
Flynn, D, Nesbitt, DJ, Ford, GA, McMeekin, P, Rodgers, H, Price, C, et al. (2015). Development of a computerised decision aid for thrombolysis in acute stroke care. BMC Med Inform Decis Mak, 15(1), 6.CrossRefGoogle ScholarPubMed
Fonarow, GC, Cox, M, Smith, E, Saver, J, Reeves, M, Bhatt, D, et al. (2017). Abstract 86: progress in achieving more rapid door-to-needle times in acute ischemic stroke: interim findings from target: stroke phase II. Stroke, 48(Suppl 1), A86.Google Scholar
Fonarow, GC, Smith, EE, Saver, JL, Reeves, MJ, Bhatt, DL, Grau-Sepulveda, MV, et al. (2011a). Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. Circulation, 123(7), 750–8.CrossRefGoogle ScholarPubMed
Fonarow, GC, Smith, EE, Saver, JL, Reeves, MJ, Hernandez, AF, Peterson, ED, et al. (2011b). Improving door-to-needle times in acute ischemic stroke: the design and rationale for the American Heart Association/American Stroke Association’s Target: Stroke initiative. Stroke, 42(10), 2983–9.CrossRefGoogle ScholarPubMed
Gadhia, J, Starkman, S, Ovbiagele, B, Ali, L, Liebeskind, D, Saver, JL. (2010). Assessment and improvement of figures to visually convey benefit and risk of stroke thrombolysis. Stroke, 41(2), 300–6.CrossRefGoogle ScholarPubMed
Goyal, M., Menon, BK, van Zwam, WH, Dippel, DW, Mitchell, PJ, Demchuk, AM, et al. (2016). Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet, 387(10029), 1723–31.CrossRefGoogle ScholarPubMed
Grotta, J. (2001). Combination therapy stroke trial: recombinant tissue-type plasminogen activator with/without lubeluzole. Cerebrovasc Dis, 12(3), 258–63.CrossRefGoogle ScholarPubMed
Hacke, W, Lyden, P, Emberson, J, Baigent, C, Blackwell, L, Albers, G, et al; Stroke Thrombolysis Trialists’ Collaborators. (2018). Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: Individual-patient-data meta-analysis of randomized trials. Int J Stroke, 13(2), 175–89.CrossRefGoogle ScholarPubMed
Higashida, R, Alberts, MJ, Alexander, DN, Crocco, TJ, Demaerschalk, BM, Derdeyn, CP, et al. (2013). Interactions within stroke systems of care: a policy statement from the American Heart Association/American Stroke Association. Stroke, 44(10), 2961–84.CrossRefGoogle ScholarPubMed
Hill, MD, Buchan, AM. (2005). Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study. CMAJ, 172(10), 1307–12.CrossRefGoogle ScholarPubMed
Hougaard, KD, Hjort, N, Zeidler, D, Sorensen, L, Norgaard, A, Hansen, TM, et al. (2014). Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: a randomized trial. Stroke, 45(1), 159–67.CrossRefGoogle ScholarPubMed
Huang, X, MacIsaac, R, Thompson, JL, Levin, B, Buchsbaum, R, Haley, EC Jr., Levi, C, et al. (2016). Tenecteplase versus alteplase in stroke thrombolysis: an individual patient data meta-analysis of randomized controlled trials. Int J Stroke, 11(5), 534–43.CrossRefGoogle ScholarPubMed
Hughes, S. (2017). NOR-TEST: tenecteplase similar to alteplase in stroke. Medscape.Google Scholar
IST-3 Collaborative Group. (2015). Association between brain imaging signs, early and late outcomes, and response to intravenous alteplase after acute ischaemic stroke in the third International Stroke Trial (IST-3): secondary analysis of a randomised controlled trial. Lancet Neurol, 14(5), 485–96.Google Scholar
Jauch, EC, Saver, JL, Adams, HP Jr., Bruno, A, Connors, JJ, Demaerschalk, BM, et al. (2013). Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 44(3), 870947.CrossRefGoogle ScholarPubMed
Kermer, P, Eschenfelder, CC, Diener, HC, Grond, M, Abdalla, Y, Althaus, K, et al. (2017). Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany – a national case collection. Int J Stroke, 12(4), 383–91.CrossRefGoogle ScholarPubMed
Khatri, P, Kleindorfer, DO, Devlin, T, Sawyer, RN Jr, Starr, M, Mejilla, J, et al.; P. Investigators. (2018). Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: the PRISMS randomized clinical trial. JAMA, 320(2), 156–66.CrossRefGoogle ScholarPubMed
Kim, BJ, Han, MK, Park, TH, Park, SS, Lee, KB, Lee, BC, et al. (2015). Low-versus standard-dose alteplase for ischemic strokes within 4.5 hours: a comparative effectiveness and safety study. Stroke, 46(9), 2541–8.CrossRefGoogle ScholarPubMed
Kim, JT, Fonarow, GC, Smith, EE, Reeves, MJ, Navalkele, DD, Grotta, JC, et al. (2017). treatment with tissue plasminogen activator in the golden hour and the shape of the 4.5-hour time-benefit curve in the national United States Get with the Guidelines-Stroke population. Circulation, 135(2), 128–39.CrossRefGoogle ScholarPubMed
Lansberg, MG, Schrooten, M, Bluhmki, E, Thijs, VN, J. L. Saver, JL. (2009). Treatment time-specific number needed to treat estimates for tissue plasminogen activator therapy in acute stroke based on shifts over the entire range of the modified Rankin Scale. Stroke, 40(6), 2079–84.CrossRefGoogle ScholarPubMed
Lees, KR, Emberson, J, Blackwell, L, Bluhmki, E, Davis, SM, Donnan, GA, et al.; Stroke Thrombolysis Trialists’ Collaborators. (2016). Effects of alteplase for acute stroke on the distribution of functional outcomes: a pooled analysis of 9 trials. Stroke, 47(9), 2373–9.CrossRefGoogle ScholarPubMed
Legrand, L, Naggara, O, Turc, G, Mellerio, C, Roca, P, Calvet, D, et al. (2013). Clot burden score on admission T2*-MRI predicts recanalization in acute stroke. Stroke, 44(7), 1878–84.CrossRefGoogle ScholarPubMed
Liberatore, GT,. Samson, A, Bladin, C, Schleuning, WD, Medcalf, RL. (2003). Vampire bat salivary plasminogen activator (desmoteplase): a unique fibrinolytic enzyme that does not promote neurodegeneration. Stroke, 34(2), 537–43.CrossRefGoogle Scholar
Lindley, RI, Wardlaw, JM, Whiteley, WN, Cohen, G, Blackwell, L, Murray, GD, et al.; ISTC Group (2015). Alteplase for acute ischemic stroke: outcomes by clinically important subgroups in the Third International Stroke Trial. Stroke, 46(3), 746–56.CrossRefGoogle ScholarPubMed
Lindsay, P, Bayley, M, McDonald, A, Graham, ID, Warner, G, Phillips, S. (2008). Toward a more effective approach to stroke: Canadian Best Practice Recommendations for Stroke Care. CMAJ, 178(11), 1418–25.CrossRefGoogle Scholar
Logallo, N, Novotny, V, Assmus, J, Kvistad, CE, Alteheld, L, Ronning, OM, et al. (2017). Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol, 16(10), 781–8.CrossRefGoogle ScholarPubMed
Lorenzano, S, Toni, D, (2017). TESPI (Thrombolysis in elderly stroke patients in Italy). Paper presented at the European Stroke Organization Conference, Prague, Czech Republic.Google Scholar
Luo, S, Zhuang, M, Zeng, W, Tao, J. (2016). Intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy: a systematic review and meta-analysis of 19 studies. J Am Heart Assoc, 5(5), e003242.CrossRefGoogle ScholarPubMed
Lyden, P, Jacoby, M, Schim, J, Albers, G, Mazzeo, P, Ashwood, T, et al. (2001). The Clomethiazole Acute Stroke Study in tissue-type plasminogen activator-treated stroke (CLASS-T): final results. Neurology, 57, 11991205.CrossRefGoogle ScholarPubMed
Ma, H, Campbell, BCV, Parsons, MW, Churilov, L, Levi, CR, Hsu, C, et al.; EXTEND Investigators. (2019). Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med, 380(19), 17951803.CrossRefGoogle ScholarPubMed
Meretoja, A, Strbian, D, Mustanoja, S, Tatlisumak, T, Lindsberg, PJ, Kaste, M. (2012). Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology, 79(4), 306–13.CrossRefGoogle ScholarPubMed
Montero, M, Tokunboh, I, Sharma, L, Szeder, SV, AM LD, Lansberg, M, et al. (2017). Harmonized visual decision aids to expedite physician, patient, and family decision-making regarding intravenous tPA for acute ischemic stroke in different time windows. Eur Stroke J, 2(IS), 155.Google Scholar
Mori, E, Minematsu, K, Nakagawara, J, Hasegawa, Y, Nagahiro, S, Okada, Y, Truelsen, T, et al.; D.-J. Investigators (2015). Safety and tolerability of desmoteplase within 3 to 9 hours after symptoms onset in Japanese patients with ischemic stroke. Stroke, 46(9), 2549–54.CrossRefGoogle ScholarPubMed
Nacu, A, Kvistad, CE, Naess, H, Oygarden, H, Logallo, N, J.Assmus, J, et al. (2017). NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study): randomized controlled contrast-enhanced sonothrombolysis in an unselected acute ischemic stroke population. Stroke, 48(2), 335–41.CrossRefGoogle Scholar
Nakagawara, J, Minematsu, K, Okada, Y, Tanahashi, N, Nagahiro, S, Mori, E, et al. (2010). Thrombolysis with 0.6 mg/kg intravenous alteplase for acute ischemic stroke in routine clinical practice: the Japan post-Marketing Alteplase Registration Study (J-MARS). Stroke, 41(9), 1984–9.CrossRefGoogle ScholarPubMed
National Institute for Health and Clinical Excellence (NICE) – National Health Services. (2007). Final appraisal determination: alteplase for the treatment of acute ischaemic stroke. Accessed October 2009.Google Scholar
NINDS t-PA Stroke Trial Study Group. (1997). Generalized efficacy of t-PA for acute stroke. Subgroup analysis of the NINDS t-PA Stroke Trial. Stroke, 28(11), 2119–25.Google Scholar
Pancioli, AM, Adeoye, O, Schmit, PA, Khoury, J, Levine, SR, Tomsick, TA, et al.; and C.-E. Investigators. (2013). Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke – enhanced regimen stroke trial. Stroke, 44(9): 2381–7.CrossRefGoogle ScholarPubMed
Pancioli, AM, Broderick, J, Brott, T, Tomsick, T, Khoury, J, Bean, J, et al. (2008). The combined approach to lysis utilizing eptifibatide and rt-PA in acute ischemic stroke: the CLEAR stroke trial. Stroke, 39(12), 3268–76.CrossRefGoogle ScholarPubMed
Parsons, M, Spratt, N, Bivard, A, Campbell, B, Chung, K, Miteff, F, et al. (2012). A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med, 366(12), 10991107.CrossRefGoogle ScholarPubMed
Picanco, MR, Christensen, S, Campbell, BC, Churilov, L, Parsons, MW, Desmond, PM, et al. (2014). Reperfusion after 4.5 hours reduces infarct growth and improves clinical outcomes. Int J Stroke, 9(3), 266–9.CrossRefGoogle ScholarPubMed
Pikija, S, Sztriha, LK, Sebastian Mutzenbach, J, Golaszewski, SM, Sellner, J. (2017). Idarucizumab in dabigatran-treated patients with acute ischemic stroke receiving alteplase: a systematic review of the available evidence. CNS Drugs, 31(9), 747–57.CrossRefGoogle ScholarPubMed
Reddrop, C, Moldrich, RX, Beart, PM, Farso, M, Liberatore, GT, Howells, DW, et al. (2005). Vampire bat salivary plasminogen activator (desmoteplase) inhibits tissue-type plasminogen activator-induced potentiation of excitotoxic injury. Stroke, 36(6), 1241–6.CrossRefGoogle ScholarPubMed
Sanossian, N. (2017). Before the angiography suite: prehospital stroke identification, routing, and treatment. Endovascular Today, 16, 4552.Google Scholar
Saposnik, G, Gladstone, D, Raptis, R, Zhou, L, Hart, RG; Investigators of the Registry of the Canadian Stroke Network and the Stroke Outcomes Research Canada Working Group. (2013). Atrial fibrillation in ischemic stroke: predicting response to thrombolysis and clinical outcomes. Stroke, 44(1), 99104.CrossRefGoogle ScholarPubMed
Saqqur, M, Tsivgoulis, G, Nicoli, F, Skoloudik, D, Sharma, VK, Larrue, V, et al. (2014). The role of sonolysis and sonothrombolysis in acute ischemic stroke: a systematic review and meta-analysis of randomized controlled trials and case-control studies. J Neuroimaging, 24(3), 209–20.CrossRefGoogle ScholarPubMed
Saver, JL. (2011). Optimal end points for acute stroke therapy trials: best ways to measure treatment effects of drugs and devices. Stroke, 42(8), 2356–62.CrossRefGoogle ScholarPubMed
Saver, JL, Fonarow, GC, Smith, EE, Reeves, MJ, Grau-Sepulveda, MV, Pan, W, et al. (2013). Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA, 309(23), 2480–8.CrossRefGoogle ScholarPubMed
Saver, JL, Gornbein, J, Grotta, J, Liebeskind, D, Lutsep, H, Schwamm, L, et al. (2009). Number needed to treat to benefit and to harm for intravenous tissue plasminogen activator therapy in the 3- to 4.5-hour window: joint outcome table analysis of the ECASS 3 trial. Stroke, 40(7), 2433–7.CrossRefGoogle ScholarPubMed
Seiffge, DJ, Hooff, RJ, Nolte, CH, Bejot, Y, Turc, G, Ikenberg, B, et al. (2015). Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome. Circulation, 132(13), 1261–9.CrossRefGoogle ScholarPubMed
Sharma, M, Clark, H, Armour, T, Stotts, G, Coté, R, Hill, MD, et al. (2005). Acute stroke: evaluation and treatment. Evid Rep Technol Assess (Summ), 127, 17.Google ScholarPubMed
Shobha, N., Fang, J, Hill, MD. (2013). Do lacunar strokes benefit from thrombolysis? Evidence from the Registry of the Canadian Stroke Network. Int J Stroke, 8 (Suppl A100), 4549.CrossRefGoogle ScholarPubMed
Thomalla, G, Simonsen, CZ, Boutitie, F, Andersen, G, Berthezene, Y, Cheng, B, et al.; W.-U. Investigators. (2018). MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med, 379(7), 611–22.CrossRefGoogle ScholarPubMed
Tong, X, Liao, X, Pan, Y, Cao, Y, Wang, C, Liu, C, et al. (2016). Intravenous thrombolysis is more safe and effective for posterior circulation stroke: Data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China). Medicine (Baltimore), 95(24), e3848.CrossRefGoogle ScholarPubMed
von Kummer, R, Mori, E, Truelsen, T, Jensen, JS, Gronning, BA, Fiebach, JB, et al. (2016). Desmoteplase 3 to 9 hours after major artery occlusion stroke: the DIAS-4 Trial (efficacy and safety study of desmoteplase to treat acute ischemic stroke). Stroke, 47(12), 2880–87.CrossRefGoogle ScholarPubMed
Wahlgren, N, Ahmed, N. (2016). SITS Report 2016. Stockholm: SITS International Coordination Team.Google Scholar
Warach, S, Al-Rawi, Y, Furlan, AJ, Fiebach, JB, Wintermark, M, Lindsten, A, et al. (2012). Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: insights from the desmoteplase in acute stroke trials. Stroke, 43(9), 2313–18.CrossRefGoogle ScholarPubMed
Wardlaw, JM, Koumellis, P, Liu, M. (2013). Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke. Cochrane Database Syst Rev, 5, CD000514.CrossRefGoogle ScholarPubMed
Wardlaw, JM, Murray, V, Berge, E, del Zoppo, GJ. (2014). Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev, 7, CD000213.CrossRefGoogle ScholarPubMed
Wechsler, LR, Demaerschalk, BM, Schwamm, LH, Adeoye, OM, Audebert, HJ, Fanale, CV, et al. (2017). Telemedicine quality and outcomes in stroke: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 48(1), e3e25.CrossRefGoogle ScholarPubMed
Wheeler, HM, Mlynash, M, Inoue, M, Tipirnini, A, Liggins, J, Bammer, R, et al. (2015). The growth rate of early DWI lesions is highly variable and associated with penumbral salvage and clinical outcomes following endovascular reperfusion. Int J Stroke, 10(5), 723–9.CrossRefGoogle ScholarPubMed
Whiteley, WN, Emberson, J, Lees, KR, Blackwell, L, Albers, G, Bluhmki, E, et al; Stroke Thrombolysis Trialists. (2016). Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis. Lancet Neurol, 15(9), 925–33.CrossRefGoogle ScholarPubMed
Wright, L, Hill, KM, Bernhardt, J, Lindley, R, Ada, L, Bajorek, BV, et al. (2012). Stroke management: updated recommendations for treatment along the care continuum. Intern Med J, 42(5), 562–9.CrossRefGoogle ScholarPubMed
Xian, Y, Federspiel, JJ, Hernandez, AF, Laskowitz, DT, Schwamm, LH, Bhatt, DL, et al. (2017a). Use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who take non-vitamin K antagonist oral anticoagulants before stroke. Circulation, 135(11), 1024–35.CrossRefGoogle ScholarPubMed
Xian, Y, Liang, L, Smith, EE, Schwamm, LH, Reeves, MJ, Olson, DM, et al. (2012). Risks of intracranial hemorrhage among patients with acute ischemic stroke receiving warfarin and treated with intravenous tissue plasminogen activator. JAMA, 307(24), 2600–8.CrossRefGoogle ScholarPubMed
Xian, Y, Xu, H, Lytle, B, Blevins, J, Peterson, ED, Hernandez, AF, et al. (2017b). Use of strategies to improve door-to-needle times with tissue-type plasminogen activator in acute ischemic stroke in clinical practice: findings from Target: Stroke. Circ Cardiovasc Qual Outcomes, 10(1).CrossRefGoogle ScholarPubMed
Yayan, J. (2013). Onset of orolingual angioedema after treatment of acute brain ischemia with alteplase depends on the site of brain ischemia: a meta-analysis. N Am J Med Sci, 5(10), 589–93.CrossRefGoogle ScholarPubMed
Zinkstok, SM, Roos, YB; ARTIS Investigators. (2012). Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet, 380(9843), 731–7.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats