Background: The beneficial effects of endovascular therapy (EVT) in acute ischemic stroke have been demonstrated in recent clinical trials using new-generation thrombectomy devices. However, the comparative effectiveness and safety of preceding intravenous thrombolysis (IVT) in this population has rarely been evaluated. Methods: From a prospective multicenter stroke registry database in Korea, we identified patients with acute ischemic stroke who were treated with EVT within 8 h of onset and admitted to 14 participating centers during 2008-2013. The primary outcome was a modified Rankin Scale (mRS) score at 3 months. Major secondary outcomes were successful recanalization defined as a modified Treatment in Cerebral Ischemia score of 2b-3, functional independence (mRS score 0-2), mortality at 3 months, and symptomatic hemorrhagic transformation (SHT) during hospitalization. Multivariable logistic regression analyses using generalized linear mixed models were performed to estimate the adjusted odds ratios (ORs) of preceding IVT. Results: Of the 639 patients (male, 61%; age 69 ± 12; National Institutes of Health Stroke Scale score of 15 [11-19]) who met the eligibility criteria, 458 received preceding IVT. These patients showed lower mRS scores (adjusted common OR, 1.38 [95% CI 0.98-1.96]). Preceding IVT was associated with successful recanalization (1.96 [1.23-3.11]) and reduced 3-month mortality (0.58 [0.35-0.97]) but not with SHT (0.96 [0.48-1.93]). Conclusion: In patients treated with EVT within 8 of acute ischemic stroke onset, preceding IVT may enhance survival and successful recanalization without additional risk of SHT, and mitigate disability at 3 months.

Keywords:
Preceding intravenous thrombolysis, Acute ischemic stroke, Comparative effectiveness research, Acute stroke therapy, Endovascular therapy, Functional outcome
1.
Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW; MR CLEAN Investigators: A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372:11-20.
2.
Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators: Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372:2296-2306.
3.
Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators: Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372:1019-1030.
4.
Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators: Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;372:1009-1018.
5.
Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators: Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015;372:2285-2295.
6.
Pfefferkorn T, Holtmannspotter M, Patzig M, Bruckmann H, Ottomeyer C, Opherk C, Dichgans M, Fesl G: Preceding intravenous thrombolysis facilitates endovascular mechanical recanalization in large intracranial artery occlusion. Int J Stroke 2012;7:14-18.
7.
Kass-Hout T, Kass-Hout O, Mokin M, Thesier DM, Yashar P, Orion D, Jahshan S, Hopkins LN, Siddiqui AH, Snyder KV, Levy EI: Is bridging with intravenous thrombolysis of any benefit in endovascular therapy for acute ischemic stroke? World Neurosurg 2014;82:e453-e458.
8.
Shi ZS, Loh Y, Walker G, Duckwiler GR; Merci and Multi MERCI Investigators: Endovascular thrombectomy for acute ischemic stroke in failed intravenous tissue plasminogen activator versus non-intravenous tissue plasminogen activator patients: Revascularization and outcomes stratified by the site of arterial occlusions. Stroke 2010;41:1185-1192.
9.
Bhatia R, Shobha N, Menon BK, Bal SP, Kochar P, Palumbo V, Wong JH, Morrish WF, Hudon ME, Hu W, Coutts SB, Barber PA, Watson T, Goyal M, Demchuk AM, Hill MD: Combined full-dose IV and endovascular thrombolysis in acute ischaemic stroke. Int J Stroke 2014;9:974-979.
10.
Broeg-Morvay A, Mordasini P, Bernasconi C, Buhlmann M, Pult F, Arnold M, Schroth G, Jung S, Mattle HP, Gralla J, Fischer U: Direct mechanical intervention versus combined intravenous and mechanical intervention in large artery anterior circulation stroke: a matched-pairs analysis. Stroke 2016;47:1037-1044.
11.
Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborators: Endovascular thrombectomy after large-vessel ischaemic stroke: A meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723-1731.
12.
Kim BJ, Park JM, Kang K, Lee SJ, Ko Y, Kim JG, Cha JK, Kim DH, Nah HW, Han MK, Park TH, Park SS, Lee KB, Lee J, Hong KS, Cho YJ, Lee BC, Yu KH, Oh MS, Kim DE, Ryu WS, Cho KH, Kim JT, Choi JC, Kim WJ, Shin DI, Yeo MJ, Sohn SI, Hong JH, Lee J, Lee JS, Yoon BW, Bae HJ: Case characteristics, hyperacute treatment, and outcome information from the clinical research center for stroke-fifth division registry in South Korea. J Stroke 2015;17:38-53.
13.
Kim BJ, Han MK, Park TH, Park SS, Lee KB, Lee BC, Yu KH, Cha JK, Kim DH, Lee J, Lee SJ, Ko Y, Park JM, Kang K, Cho YJ, Hong KS, Cho KH, Kim JT, Kim DE, Lee J, Lee JS, Jang MS, Broderick JP, Yoon BW, Bae HJ; CRCS-5 investigators: Current status of acute stroke management in Korea: a report on a multicenter, comprehensive acute stroke registry. Int J Stroke 2014;9:514-518.
14.
Noser EA, Shaltoni HM, Hall CE, Alexandrov AV, Garami Z, Cacayorin ED, Song JK, Grotta JC, Campbell MS 3rd: Aggressive mechanical clot disruption: a safe adjunct to thrombolytic therapy in acute stroke? Stroke 2005;36:292-296.
15.
Zaidat OO, Yoo AJ, Khatri P, Tomsick TA, von Kummer R, Saver JL, Marks MP, Prabhakaran S, Kallmes DF, Fitzsimmons BF, Mocco J, Wardlaw JM, Barnwell SL, Jovin TG, Linfante I, Siddiqui AH, Alexander MJ, Hirsch JA, Wintermark M, Albers G, Woo HH, Heck DV, Lev M, Aviv R, Hacke W, Warach S, Broderick J, Derdeyn CP, Furlan A, Nogueira RG, Yavagal DR, Goyal M, Demchuk AM, Bendszus M, Liebeskind DS; Cerebral Angiographic Revascularization Grading (CARG) Collaborators; STIR Revascularization working group; STIR Thrombolysis in Cerebral Infarction (TICI) Task Force: Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke 2013;44:2650-2663.
16.
Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D; ECASS Investigators: Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359:1317-1329.
17.
Saver JL: Novel end point analytic techniques and interpreting shifts across the entire range of outcome scales in acute stroke trials. Stroke 2007;38:3055-3062.
18.
Lansberg MG, Dabus G: Interaction between time to treatment and reperfusion therapy in patients with acute ischemic stroke. J Neurointerv Surg 2013;5(suppl 1):i48-i51.
19.
Kufner A, Nolte CH, Galinovic I, Brunecker P, Kufner GM, Endres M, Fiebach JB, Ebinger M: Smoking-thrombolysis paradox: recanalization and reperfusion rates after intravenous tissue plasminogen activator in smokers with ischemic stroke. Stroke 2013;44:407-413.
20.
Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, Clark W, Budzik R, Zaidat OO; SWIFT Trialists: 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.
21.
Rha JH, Saver JL: The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke 2007;38:967-973.
22.
Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS, Lutsep HL, Rymer MM, Higashida RT, Starkman S, Gobin YP; Multi MERCI Investigators, Frei D, Grobelny T, Hellinger F, Huddle D, Kidwell C, Koroshetz W, Marks M, Nesbit G, Silverman IE: Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke 2008;39:1205-1212.
23.
Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S: Recombinant tissue-type plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS study: a randomized controlled trial. Alteplase thrombolysis for acute noninterventional therapy in ischemic stroke. JAMA 1999;282:2019-2026.
24.
Chao AC, Hsu HY, Chung CP, Liu CH, Chen CH, Teng MM, Peng GS, Sheng WY, Hu HH; Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study Group: Outcomes of thrombolytic therapy for acute ischemic stroke in Chinese patients: the Taiwan thrombolytic therapy for acute ischemic stroke (TTT-AIS) study. Stroke 2010;41:885--890.
25.
Yamaguchi T, Mori E, Minematsu K, Nakagawara J, Hashi K, Saito I, Shinohara Y; Japan Alteplase Clinical Trial (J-ACT) Group: Alteplase at 0.6 mg/kg for acute ischemic stroke within 3 hours of onset: Japan alteplase clinical trial (J-ACT). Stroke 2006;37:1810-1815.
26.
Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, Ajani Z, Feng L, Meyer BC, Olson S, Schwamm LH, Yoo AJ, Marshall RS, Meyers PM, Yavagal DR, Wintermark M, Guzy J, Starkman S, Saver JL; MR RESCUE Investigators: A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 2013;368:914-923.
27.
Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, Jauch EC, Jovin TG, Yan B, Silver FL, von Kummer R, Molina CA, Demaerschalk BM, Budzik R, Clark WM, Zaidat OO, Malisch TW, Goyal M, Schonewille WJ, Mazighi M, Engelter ST, Anderson C, Spilker J, Carrozzella J, Ryckborst KJ, Janis LS, Martin RH, Foster LD, Tomsick TA; Interventional Management of Stroke (IMS) III Investigators: Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013;368:893-903.
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