Intravenous recombinant tissue plasminogen activator continues to be first-line therapy for patients with acute ischemic stroke presenting within the appropriate time window, but one potential limitation is the low rate of recanalization in the setting of large artery occlusions. Intra-arterial (IA) treatment is effective for emergency revascularization of proximal intracranial arterial occlusions, but proof of benefit has been lacking until recently. Our goal is to outline the history of endovascular therapy and review both IA thrombolysis and mechanical interventions. In addition, we will discuss the impact of important trials such as the Third Interventional Management of Stroke (IMS3) trial, and the more recent trials Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) on acute stroke management and the implications for the practicing neurohospitalist.
XuJKKennethDMurphySLTejada-VeraB. Deaths: final data for 2007. Natl Vital Stat Rep. 2010;58(19):1–19.
2.
MullenMTPisapiaJMTilwaSMesséSRSteinSC. Systematic review of outcome after ischemic stroke due to anterior circulation occlusion treated with intravenous, intra-arterial, or combined intravenous + intra-arterial thrombolysis. Stroke. 2012;43(9):2350–2355.
3.
KharitonovaTAhmedNThorenM. Hyperdense middle cerebral artery sign on admission CT scan—prognostic significance for ischaemic stroke patients treated with intravenous thrombolysis in the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Register. Cerebrovasc Dis. 2009;27(1):51–59.
4.
Abul-KasimKBrizziMPeterssonJ. Hyperdense middle cerebral artery sign is an ominous prognostic marker despite optimal workflow. Acta Neurol Scand. 2010;122(2):132–139.
5.
SmithWSTsaoJWBillingsME. Prognostic significance of angiographically confirmed large vessel intracranial occlusion in patients presenting with acute brain ischemia. Neurocrit Care. 2006;4(1):14–17.
6.
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(24):1581–1587.
7.
HackeWKasteMBluhmkiE. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317–1329.
8.
Del ZoppoGJSaverJLJauchECAdamsHPJr. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke. 2009;40(8):2945–2948.
9.
MeschiaJFBarrettKMBrottTG. Reperfusion therapy for acute ischemic stroke: how should we react to the Third Interventional Management of Stroke (IMS III) trial?Mayo Clin Proc. 2013;88(7):653–657.
10.
JauchECSaverJLAdamsHPJr. 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. 2013;44(3):870–947.
11.
BhatiaRHillMDShobhaN. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke. 2010;41(10):2254–2258.
12.
ChristouIFelbergRADemchukAM. Intravenous tissue plasminogen activator and flow improvement in acute ischemic stroke patients with internal carotid artery occlusion. J Neuroimaging. 2002;12(2):119–123.
13.
ZangerleAKiechlSSpiegelM. Recanalization after thrombolysis in stroke patients: predictors and prognostic implications. Neurology. 2007;68(1):39–44.
14.
RhaJHSaverJL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke. 2007;38(3):967–973.
15.
HaleyECJrThompsonJLGrottaJC. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke. 2010;41(4):707–711.
16.
ParsonsMSprattNBivardA. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med. 2012;366(12):1099–1107.
17.
DemchukAMFelburgRAAlexandrovAV. Clinical recovery from acute ischemic stroke after early reperfusion of the brain with intravenous thrombolysis. N Engl J Med. 1999;340(11):894.
18.
AlexandrovAVDemchukAMFelbergRA. High rate of complete recanalization and dramatic clinical recovery during tPA Infusion when continuously monitored with 2-MHz transcranial Doppler monitoring. Stroke. 2000;31(3):610–614.
19.
AlexandrovAVMolinaCAGrottaJC. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med. 2004;351(21):2170–2178.
PancioliAMAdeoyeOSchmitPA. Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial. Stroke. 2013;44(9):2381–2387.
22.
ZinkstokSMRoosYB; ARTIS Investigators. Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomized controlled trial. Lancet. 2012;380(9843):731–737.
23.
WardlawJMKoumellisPLiuM. Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke. Cochrane Database Syst Rev. 2013;5:CD000514.
24.
MeyersPMSchumacherHCConnollyESJrHeyerEJGrayWAHigishadaRT. Current status of endovascular stroke treatment. Circulation. 2011;123(22):2591–2601.
25.
CicconeAdel ZoppoGJ. Evolving role of endovascular treatment of acute ischemic stroke. Curr Neurol Neurosci Rep. 2014;14(1):416.
26.
BroderickJPPaleschYYDemchukAM. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013;368(10):893–903.
27.
TomsickTAKhatriPJovinT. Equipoise among recanalization strategies. Neurology. 2010;74(13):1069–1076.
28.
TonarelliSBTibbsMVazquezG. Accuracy of the new ICD-9-CM code for “drip-and-ship” thrombolytic treatment in patients with ischemic stroke. J Stroke Cerebrovasc Dis. 2012;21(2):121–123.
29.
del ZoppoGJHigashidaRTFurlanAJ. PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. Stroke. 1998;29(1):4–11.
30.
FurlanAHigashidaRWechslerL. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999;282(21):2003–2011.
31.
MeyersPMSchumacherHCConnollyESJrHeyerEJGrayWAHigashidaRT. Current status of endovascular stroke treatment. Circulation. 2011;123(22):2591–2601.
32.
SmithWSSungGSaverJ. Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke. 2008;39(4):1205–1212.
33.
Penumbra Pivotal Stroke Trial Investigators. The Penumbra Pivotal Stroke Trial: safety and effectiveness of a new generation of mechanical devices for clot removal in intracranial large vessel occlusive disease. Stroke. 2009;40(8):2761–2768.
34.
LevyEIEckerRDHorowitzMB. Stent-assisted intracranial recanalization for acute stroke: early results. Neurosurgery. 2006;58(3):458–463.
35.
LevyEIMehtaRGuptaR. Self-expanding stents for recanalization of acute cerebrovascular occlusions. AJNR Am J Neuroradiol. 2007;28(5):816–822.
36.
NogueiraRGLutsepHLGuptaR. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet. 2012;380(9849):1231–1240.
37.
SaverJLJahanRLevyEI. 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(9849):1241–1249.
38.
LewandowskiCAFrankelMTomsickTA. Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial. Stroke. 1999;30(12):2598–2605.
39.
IMS Study Investigators. Combined intravenous and intra-arterial recanalization for acute ischemic stroke: the Interventional Management of Stroke Study. Stroke. 2004;35(4):904–911.
40.
BerkhemerOAFransenPSBeumerD. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11–20.
41.
DemchukAMGoyalMMenonBK. Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times (ESCAPE) trial: methodology. Int J Stroke. 2015;10(3):429–438.
42.
GoyalMDemchukAMMenonBK. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019–1030.
43.
CampbellBCMitchellPJKleinigTJ. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009–1018.
44.
SaverJLGoyalMBonafeA. Solitaire™ with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke. Int J Stroke. 2015;10(3):439–448.
GoASMozaffarianDRogerVL. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation. 2012;127(1):e6–e245.
53.
PrabhakaranSSoltanolkotabiMHonarmandAR. Perfusion-based selection for endovascular reperfusion therapy in anterior circulation acute ischemic stroke. Am J Neuroradiol. 2014;35(7):1303–1308.
54.
YeoLLLPaliwalPTeohHL. Timing of recanalization after intravenous thrombolysis and functional outcomes after acute ischemic stroke. JAMA Neurol. 2013;70(3):353.
55.
CicconeAValvassoriL. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013;368(25):2433–2434.
56.
KidwellCSJahanRGornbeinJ. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013;368(10):914–923.
57.
IMS II trial investigators. The International Management of Stroke (IMS) II study. Stroke. 2007;38(7):2127–2135.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
