Letter to the Editor Intravenous Versus Intra-arterial Thrombolysis for Anterior Circulation Stroke Secondary to Large Vessel Occlusion Dear Editor, I have read, with great interest, a recently published article in the Journal of Stroke and Cerebrovascular Diseases by Sallustio et al titled ‘Intra-arterial Thrombectomy versus Standard Intravenous Thrombolysis in Patients with Anterior Circulation Stroke Caused by Intracranial Arterial Occlusions: A Single-center Experience.’1 This study compared the radiographic and clinical outcomes of 51 patients who underwent intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rtPA) with 46 patients who underwent intra-arterial thrombolysis (IAT) with Penumbra System clot aspiration device (Penumbra, Alameda, CA) with or without the Solitaire stentriever device (ev3, Irvine, CA). All patients had a National Institutes of Health Stroke Scale (NIHSS) score between 8 and 24 and had imaging (computed tomography angiography) defined large vessel occlusion (LVO) of the internal carotid artery, middle cerebral artery, or both. The IVT patients were treated within a 4.5-hour window, and the IAT patients were treated within a 6-hour window. IAT patients who presented within 4.5 hours were bridged with IVT (n 5 16), and those who presented between 4.5 and 6 hours or had contraindications to receiving rtPA were treated with IAT alone (n 5 30). The patient demographics and NIHSS scores at presentation were similar between the IVT and IAT cohorts. The time interval from symptom onset to treatment was longer in the IAT cohort (P 5 .001). A recanalization of thrombolysis in myocardial infarction grade 2 or higher was achieved in 94% of IAT patients compared with 45% of IVT patients (P , .0001). In the IAT arm, the Solitaire stentriever was used in 50% of cases, and the procedural complication rate was 11%. Although the incidence of any post-treatment intracranial hemorrhage was higher in the IAT arm (P 5 .03), the rates of symptomatic intracranial hemorrhage were similar between the 2 cohorts. An improvement in the NIHSS score of at least 8 points was observed more frequently in the IAT cohort than that in the IVT cohort at 24 hours after symptom onset (26% versus 10%; P 5 .03). At discharge, the degree of improvement in the NIHSS score compared with presentation was significantly higher in the IAT cohort (P 5 .001),

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although the proportions of patients with good functional outcome (modified Rankin Scale score of 0-2) and the mortality rates were similar between the 2 groups. At 3 months follow-up, there was no difference between the IVT and IAT cohorts in NIHSS scores, functional outcomes, or mortality rates. The results of this study are consistent with 3 recently published randomized controlled trials (RCTs) in the New England Journal of Medicine, Interventional Management of Stroke III (IMS III), Mechanical Retrieval and Recanalization of Stroke Clots (MR RESCUE), and Local Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS) Expansion, which failed to demonstrate superiority of mechanical thrombectomy over standard of care IVT.2-4 Criticisms of these trials include failure to give IVT or administration of substandard rtPA doses to patients who underwent intervention, which is contraindicated by level I evidence, use of first-generation devices such as the Merci Retriever (Concentric Medical, Mountain View, CA), failure to obtain acceptable rates of reperfusion, delay in delivering IAT, and lack of pretreatment angiographic imaging to identify the presence of LVO.5 Two RCTs, Solitaire With the Intention For Thrombectomy (SWIFT) and Thrombectomy Revascularization of large Vessel Occlusions in acute ischemic stroke (TREVO 2), have demonstrated superior angiographic and clinical outcomes for stentrievers, such as the Solitaire and Trevo (Concentric Medical) devices, compared with the Merci Retriever.6,7 Given the dismal reperfusion rates associated with IVT for LVO and the extremely poor prognosis of patients presenting with ischemic stroke secondary to LVO, aggressive intervention with endovascular thrombectomy has been championed.8 However, studies such as the present one, although it is nonrandomized and retrospective, temper one’s enthusiasm for the promise of newer generation endovascular technologies. The high rate of reperfusion achieved with IAT failed to translate into improved neurologic function at 3 months of follow-up. Until future RCTs demonstrate superiority of IAT over IVT, there will remain a healthy skepticism regarding the benefit of endovascular intervention for acute ischemic stroke. Additionally, further efforts are necessary to bridge the gap between post-treatment angiographic and clinical outcomes in stroke patients. Pharmacologic inhibition of the postsynaptic density protein 95 has recently been shown in primate studies to afford neuroprotection after ischemic stroke via abrogation of neurotoxic signaling pathways.9

Journal of Stroke and Cerebrovascular Diseases, Vol. 24, No. 3 (March), 2015: pp 718-719

LETTER TO THE EDITOR

Dale Ding, MD Department of Neurological Surgery University of Virginia Charlottesville, Virginia E-mail: [email protected] http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.01.023

References 1. Sallustio F, Koch G, Di Legge S, et al. Intra-arterial thrombectomy versus standard intravenous thrombolysis in patients with anterior circulation stroke caused by intracranial arterial occlusions: a single-center experience. J Stroke Cerebrovasc Dis 2013;22:e323-e331. 2. 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. 3. Ciccone A, Valvassori L, Nichelatti M, et al. Endovascular treatment for acute ischemic stroke. N Engl J Med 2013; 368:904-913.

719 4. 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. 5. Khalessi AA, Fargen KM, Lavine S, et al. Commentary: societal statement on recent acute stroke intervention trials: results and implications. Neurosurgery 2013; 73:E375-E379. 6. 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. 7. 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. 8. 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. 9. Cook DJ, Teves L, Tymianski M. Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature 2012;483:213-217.

Intravenous versus intra-arterial thrombolysis for anterior circulation stroke secondary to large vessel occlusion.

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