Intra-arterial treatment for acute ischemic stroke: a meta-analysis
Objective: To assess the potential benefit of treating patients with acute ischemic stroke using intra-arterial methods.
Methods: A meta-analysis of published randomized controlled trials that compared standard therapy with intravenous tissue plasminogen activator (IVtPA) for thrombolysis to intra-arterial therapies in patients with acute stroke was performed. All studies reported were analyzed as one group and studies documenting patients with large vessel obstruction were analyzed as a second group. The standardized mean difference (SMD) and the odds ratio (OR) of the dichotomized outcomes of Modified Rankin Scale (mRS) of these trials was calculated.
Results: Nine trials were identified with 2,711 patients treated. Meta-analysis of all studies, with and without large vessel obstruction documented, showed a significant benefit with intra-arterial therapy (SMD: 0.22 + 0.041; P=0.003). The dichotomized outcomes of mRS of these trials showed significant improvement (OR: 1.66 -2.43 in four of the five treatment arm groups examined). Meta-analysis of all publications with large vessel obstruction documented as an entry criteria showed a greater significant benefit with intra-arterial therapy (SMD: 0.35 + 0.05; P<0.001). The dichotomized outcomes of mRS of these trials showed significant improvement (OR: 1.36 -2.38 in all five treatment arm groups examined). Some heterogeneity was observed between studies.
Conclusion: Treatment of patients with acute ischemic stroke was associated with improved outcomes as measured by mRS. Patient selection, standard treatment, and study treatment factors contributed to the statistical evaluation of inter study heterogeneity and may have contributed to different study outcomes.
2. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N. Engl. J. Med. 1995;333:1581–1587.
3. Chiu D, Krieger D, Villar-Cordova C, Kasner SE, Morgenstern LB, Bratina PL, et al. Intravenous tissue plasminogen activator for acute ischemic stroke: feasibility, safety, and efficacy in the first year of clinical practice. Stroke J. Cereb. Circ. 1998;29:18-22.
4. Wang DZ, Rose JA, Honings DS, Garwacki DJ, Milbrandt JC. Treating Acute Stroke Patients With Intravenous tPA: The OSF Stroke Network Experience. Stroke. 2000;33:77–81.
5. Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al. Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke. N. Engl. J. Med. 2008;359:1317–1329.
6. Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation. 2007;115:e478-534.
7. Broderick JP, Schroth G. What the SWIFT and TREVO II trials tell us about the role of endovascular therapy for acute stroke. Stroke J. Cereb. Circ. 2013;44:1761–1764.
8. Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, Walker GA, 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.
9. Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, 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.
10. Nam J, Jing H, O’Reilly D. Intra-arterial thrombolysis vs. standard treatment or intravenous thrombolysis in adults with acute ischemic stroke: a systematic review and meta-analysis. Int. J. Stroke Off. J. Int. Stroke Soc. 2015;10.
11. del Zoppo GJ, Higashida RT, Furlan AJ, Pessin MS, Rowley HA, Gent M. PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in Acute Cerebral Thromboembolism. Stroke J. Cereb. Circ. 1998;29:4-11.
12. 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.
13. Ducrocq X, Bracard S, Taillandier L, Anxionnat R, Lacour JC, Guillemin F, et al. Comparison of intravenous and intra-arterial urokinase thrombolysis for acute ischaemic stroke. J. Neuroradiol. J. Neuroradiol. 2005;32.
14. Macleod MR, Davis SM, Mitchell PJ, Gerraty RP, Fitt G, Hankey GJ, et al. Results of a multicentre, randomised controlled trial of intra-arterial urokinase in the treatment of acute posterior circulation ischaemic stroke. Cerebrovasc. Dis. Basel Switz. 2005;20:12–17.
15. Ogawa A, Mori E, Minematsu K, Taki W, Takahashi A, Nemoto S, et al. Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke: the middle cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan. Stroke J. Cereb. Circ. 2007;38:2633–2639.
16. Van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke J. Cereb. Circ. 1988;19:604–607.
17. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 website. 2011. www.cochrane-handbook.org Accessed August 1, 2015.
18. Sen S, Huang DY, Akhavan O, Wilson S, Verro P, Solander S. IV vs. IA TPA in acute ischemic stroke with CT angiographic evidence of major vessel occlusion: a feasibility study. Neurocrit. Care 2009;11:76-81.
19. Lewandowski CA, Frankel M, Tomsick TA, Broderick J, Frey J, Clark W, et al. Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial. Stroke J. Cereb. Circ. 1999;30:2598–2605.
20. Ciccone A, Valvassori L, Ponzio M, Ballabio E, Gasparotti R, Sessa M, et al. Intra-arterial or intravenous thrombolysis for acute ischemic stroke? The SYNTHESIS pilot trial. J. Neurointerventional Surg. 2010;2:74–79.
21. Ciccone A, Valvassori L, SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N. Engl. J. Med. 2013;368:904–913.
22. Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N. Engl. J. Med. 2013;368:914–923.
23. Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N. Engl. J. Med. 2013:368.
24. Demchuk AM, Goyal M, Yeatts SD, Carrozzella J, Foster LD, Qazi E, et al. Recanalization and clinical outcome of occlusion sites at baseline CT angiography in the Interventional Management of Stroke III trial. Radiology. 2014;273:202–210.
25. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N. Engl. J. Med. 2015;372.
26. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N. Engl. J. Med. 2015;372:1019–1030.
27. Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, et al. Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection. N. Engl. J. Med. 2015;372:1009–1018.
28. Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N. Engl. J. Med. 2015;372:2296–2306.
29. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N. Engl. J. Med. 2015;372:2285–2295.
30. Menon BK, Campbell BCV, Levi C, Goyal M. Role of imaging in current acute ischemic stroke workflow for endovascular therapy. Stroke J. Cereb. Circ. 2015;46:1453–1461.
31. Akins PT, Amar AP, Pakbaz RS, Fields JD. Complications of endovascular treatment for acute stroke in the SWIFT trial with solitaire and Merci devices. AJNR Am. J. Neuroradiol. 2014;35:524–528.
32. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al. Supplement. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N. Engl. J. Med. 2015;372.
33. van den Berg LA, Koelman DL, Berkhemer OA, Rozeman AD, Fransen PS, Beumer D, et al. Type of anesthesia and differences in clinical outcome after intra-arterial treatment for ischemic stroke. Stroke J. Cereb. Circ. 2015;46: 1257–1262.
34. Freeman WD, Dhakal LP, Diaz-Gomez J. Intraarterial treatment for acute ischemic stroke. N. Engl. J. Med. 2015;372:1177–1178.
35. Ma Q, Chu C, Song H. Intravenous versus intra-arterial thrombolysis in ischemic stroke: a systematic review and meta-analysis. PloS One. 2015;10.
36. Lansberg MG, Straka M, Kemp S, Mlynash M, Wechsler LR, Jovin TG, et al. MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study. Lancet Neurol. 2012;11:860–867.
37. Inoue M, Mlynash M, Straka M, Lansberg MG, Zaharchuk G, Bammer R, et al. Patients with the malignant profile within 3 hours of symptom onset have very poor outcomes after intravenous tissue-type plasminogen activator therapy. Stroke J. Cereb. Circ. 2012;43:2494–2496.
38. Yoo AJ, Chaudhry ZA, Nogueira RG, Lev MH, Schaefer PW, Schwamm LH, et al. Infarct volume is a pivotal biomarker after intra-arterial stroke therapy. Stroke J. Cereb. Circ. 2012;43:1323–1330.
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