Introduction: In patients undergoing interventional treatment for acute ischemic stroke (AIS), proximal arterial stenosis may hinder access to the arterial occlusive lesion (AOL), compromise inflow during the intervention and prolong events leading to cerebral reperfusion. We examined proximal arterial stenosis in the Interventional Management of Stroke (IMS)-III trial, hypothesizing that it would impede successful endovascular therapy for AIS and worsen outcomes.

Methods: We reviewed 369 patients from the prospective, randomized IMS-III trial who received both IV rt-PA and intra-arterial treatment for AIS. Degree of ipsilateral extracranial internal carotid artery (EC-ICA) stenosis was determined by pre-treatment digital subtraction angiogram. We compared those with EC-ICA stenosis <70% vs. patients with stenosis =70%; statistical significance was determined by T-test. Outcome measures included mean infarct volume (MIV), mean time to reperfusion, rates of symptomatic intracerebral hemorrhage (sICH), mean modified Rankin score (mRS) at 90 days, and the percentage of patients with mRS 0-2 at 90 days.

Results: When compared to those with =70% stenosis, patients with <70% stenosis had a lower mean mRS at 90 days (2.9 vs 3.3, p=0.10), greater percentage of mRS 0-2 (43.5 vs 34.3%, p=0.15), smaller MIV (70.1 vs 87.6mL, p=0.18), shorter mean time to reperfusion (78.7 vs 105.7 minutes, p=0.002), and a higher rate of sICH (7.3 vs 2.7%, p=0.15).

Conclusions: In patients receiving combined IV/IA treatment for AIS within the IMS-III trial, ipsilateral EC-ICA stenosis of =70% significantly delayed reperfusion by an average of 26 min. This resulted in trends favoring larger infarct volumes with worse clinical outcomes despite a lower rate of sICH. This substantial treatment delay likely stems from a combination of difficult microcatheter access across the stenosis, the addition of intermediate steps to manage the stenosis (i.e. balloon angioplasty), and the restrictive effect of the stenosis on inflow in patients treated by thrombolysis.

Patient Care: This information quantifies the effect of ipsilateral carotid stenosis on the ability to reperfuse acute ischemic stroke territory. In light of studies that have shown substantial improvement in outcomes for patients with expedient reperfusion, it is imperative to understand conditions that will cause significant delays in order to encourage future study and technical improvement in treating these patients. This is the largest cohort of patients studied on this topic to date.

Learning Objectives: 1) Recognize the delay in reperfusion in endovascular stroke treatment with severe ipsilateral ICA stenosis. 2) Understand potential mechanisms for this therapeutic delay 3) Recognize the need for further study and technical improvement in treating AIS with severe ICA stenosis.

References: 1. Khatri P, Yeatts SD, Mazighi M, Broderick JP, Liebeskind DS, Demchuck AM, et al. Time to angiographic reperfusion and clinical outcome after acute ischemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial. Lancet Neurol. 2014;13:567-574. 2. Khatri P, Yeatts SD, Mazighi M, Broderick JP, Liebeskind DS, Demchuk AM, et al. The timing of angiographic reperfusion is highly associated with good clinical outcome in acute ischemic stroke. Lancet Neurol. 2014;13:567-574. 3. Tomsick TA, Yeatts SD, Liebeskind DS, Carrozzella J, Foster L, Goyal M, et al. Endovascular revascularization results in IMS III: intracranial ICA and M1 occlusions. [published online ahead of print October 23, 2014]. J Neurointerv Surg. 2014. http://jnis.bmj.com.proxy.libraries.uc.edu/content/early/2014/10/23/neurintsurg-2014-011318.long. Accessed February 24, 2015. 4. Fargen KM, Meyers PM, Khatri P, Mocco J. Improvements in recanalization with modern stroke therapy: a review of prospective ischemic stroke trials during the last two decades. J NeuroIntervent Surg. 2013;5:506-511. 5. Marks MP, Lansberg MG, Mlynash M, Kemp S, McTaggart RA, Zaharchuk G, et al. Angiographic outcome of endovascular stroke therapy correlated with MR findings, infarct growth, and clinical outcome in the DEFUSE 2 trial. Int J Stroke. 2014;9:860-865. 6. Rha J, Saver JL. The Impact of Recanalization on Ischemic Stroke Outcome: A Meta-Analysis. Stroke. 2007;38:967-973. 7. 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. 8. Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS, et al. Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke. 2008;39:1205-1212. 9. 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;40:2761-2768. 10. Khatri P, Neff J, Broderick JP, Khoury JC, Carrozzella J, Tomsick T. Revascularization end points in stroke interventional trials: recanalization versus reperfusion in IMS-I. Stroke. 2005;36:2400-2403. 11. The IMS II Trial Investigators. The Interventional Management of Stroke (IMS) II study. Stroke. 2007;38:2127–2135. 12. Broderick JP, Schroth G. What the SWIFT and TREVO II trials tell us about the role of endovascular therapy for acute stroke. Stroke 2013;44:1761–1764. 13. Tomsick T, Broderick J, Carrozella J, Khatri P, Hill M, Palesch Y, et al. Revascularization results in the interventional management of stroke II trial. AJNR Am J Neuroradiol. 2008;29:582-587. 14. Akins PT, Amar AP, Pakbaz RS, Fields JD, SWIFT Investigators. Complications of endovascular treatment for acute stroke in the SWIFT trial with solitaire and Merci devices. AJNR. 2014;35:524–28. 15. Meyers PM, Schumacher HC, Connolly, Jr ES, Heyer EJ, Gray WA, Higashida RT. Current status of endovascular stroke treatment. Circulation. 2011;123(22):2591-2601. 16. Mokin M, Snyder KV, Siddiqui AH, Hopkins LN, Levy EI. Endovascular management and treatment of acute ischemic stroke. Neurosurg Clin N Am. 2014;25:583-592. 17. Khatri P, Hill MD, Palesch YY, Spilker J, Jauch EC, Carrozzella JA, et al. Methodology of the Interventional Management of Stroke (IMS)III Trial. Int J Stroke. 2008;3(2):130-137. 18. Ferguson GG, Eliasziw M, Barr HWK, Clagett GP, Barnes RW, Wallace MC, et al. The North American Symptomatic Carotid Endarterectomy Trial: Surgical Results in 1415 Patients. Stroke. 1999;30:1751-1758. 19. Malik AM, Vora NA, Lin R, Zaidi SF, Aleu A, Jankowitz BT, et al. Endovascular Treatment of Tandem Extracranial/Intracranial Anterior Circulation Occlusions: Preliminary Single-Center Experience. Stroke. 2011;42:1653-1657