Review Article

Endovascular (Intraarterial) Treatment of Acute Ischemic Stroke: Efficacy Not Supported by Clinical Trials

Authors: William J. Powers, MD

Abstract

Intravenous tissue plasminogen activator (IV tPA, alteplase) provides a statistically and clinically significant improvement in clinical outcome for carefully selected patients with acute ischemic stroke when administered within 4.5 hours of onset; however, even within the 4.5-hour window, outcome is poor for some eligible patients, including those with occlusions of large arteries (internal carotid, middle cerebral, and basilar) and many patients do not meet the stringent eligibility criteria, especially the time requirement. Intraarterial (also known as endovascular or neurointerventional) therapies have been developed to address these needs. This review summarizes the current evidence for the efficacy of endovascular treatments in acute ischemic stroke. Randomized controlled clinical trials of acute ischemic stroke do not show any added clinical benefit of endovascular treatment over IV tPA alone in IV tPA-eligible patients, even in patients with persistent large-artery occlusion, nor have these trials provided evidence of clinical benefit in patients ineligible for IV tPA because they are >4.5 hours from onset, even if selected by sophisticated neuroimaging. The newstent retrievers, however, were rarely used in these trials. It remains to be determined from trials with direct head-to-head comparisons whether these new devices are superior to standard nonendovascular therapy. If there is a role for endovascular treatment of acute ischemic stroke, it is for patients who can be treated under 4.5 hours but who are ineligible for IV tPA because of increased hemorrhage risk from systemic thrombolytic drug effects, although this remains unproven.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics-2013 update: a report from the American Heart Association. Circulation 2013;127:e6-e245.
 
2. 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;333:1581-1587.
 
3. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359:1317-1329.
 
4. Ingall TJ, O’Fallon WM, Asplund K, et al. Findings from the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial. Stroke 2004;35:2418-2424.
 
5. Hertzberg V, Ingall T, O’Fallon W, et al. Methods and processes for the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial. Clin Trials 2008;5:308-315.
 
6. Lees KR, Bluhmki E, von Kummer R, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010;375:1695-1703.
 
7. Saqqur M, Uchino K, Demchuk AM, et al. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke 2007;38:948-954.
 
8. Guyatt GH, Haynes RB, Jaeschke RZ, et al. Users’ Guides to the Medical Literature: XXV. Evidence-based medicine: principles for applying the Users’ Guides to patient care. Evidence-Based Medicine Working Group. JAMA 2000;284:1290-1296.
 
9. Abbott JD, Jones DM, Painter MJ, et al. The epidemiology of meningococcal infectionsin England and Wales, 1912Y1983.J Infect1985;11:241-257.
 
10. Harwood R. Diabetic acidosis; results of treatment in 67 consecutive cases. N Engl J Med 1951;245:1-9.
 
11. Clark WM, Wissman S, Albers GW, et al. 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.
 
12. Levy DE, del Zoppo GJ, Demaerschalk BM, et al. Ancrod in acute ischemic stroke: results of 500 subjects beginning treatment within 6 hours of stroke onset in the ancrod stroke program. Stroke 2009;40:3796-3803.
 
13. Hacke W, Furlan AJ, Al-Rawi Y, et al. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol 2009; 8:141-150.
 
14. Minematsu K, Yamaguchi T, Omae T. ‘‘Spectacular shrinking deficit’’: rapid recovery from a major hemispheric syndrome by migration of an embolus. Neurology 1992;42:157-162.
 
15. Sandercock PA, Counsell C, Kamal AK. Anticoagulants for acute ischaemic stroke. Cochrane Database Syst Rev 2008;4:CD000024.
 
16. Powers WJ, Clarke WR, Grubb RL Jr, et al. Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial. JAMA 2011;306:1983-1992.
 
17. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011;365:993-1003.
 
18. Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled? Ann Intern Med 1996;125:605-613.
 
19. van Swieten JC, Koudstaal PJ, Visser MC, et al. Interobserver agreement for the assessment of handicap in stroke patients.Stroke1988;19:604-607.
 
20. Quinn TJ, Dawson J, Walters MR, et al. Functional outcome measures in contemporary stroke trials. Int J Stroke 2009;4:200-205.
 
21. Banks JL, Marotta CA. Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis. Stroke 2007;38:1091-1096.
 
22. Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017-1025.
 
23. del Zoppo GJ, Higashida RT, Furlan AJ, et al. 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 1998;29:4-11.
 
24. Furlan A, Higashida R, Wechsler L, 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.
 
25. Ogawa A, Mori E, Minematsu K, 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 2007;38:2633-2639.
 
26. Powers WJ. Thromobolysis for acute ischemic stroke: is intra-arterial better than intravenous? A treatment effects model. J Stroke Cerebrovasc Dis 2012;21:401-403.
 
27. Ciccone A, Valvassori L, Ponzio M, et al. Intra-arterial or intravenous thrombolysis for acute ischemic stroke? The SYNTHESIS pilot trial. J Neurointerv Surg 2010;2:74-79.
 
28. Ciccone A, Valvassori L, Nichelatti M, et al. Endovascular treatment for acute ischemic stroke. N Engl J Med 2013;368:904-913.
 
29. Becker KJ, Brott TG. Approval of the MERCI clot retriever: a critical view. Stroke 2005;36:400-403.
 
30. 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.
 
31. 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.
 
32. Powers WJ. Imaging preventable infarction in patients with acute ischemic stroke. AJNR Am J Neuroradiol 2008;29:1823-1825.
 
33. Powers WJ. Perfusion-diffusion mismatch: does it identify who will benefit from reperfusion therapy? Trans Stroke Res 2013;3:182-187.
 
34. 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.
 
35. 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.
 
36. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-1339.
 
37. Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996;143:1-13.
 
38. Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008;359:1238-1251.
 
39. Lindsberg PJ, Mattle HP. Therapy of basilar artery occlusion: a systematic analysis comparing intra-arterial and intravenous thrombolysis. Stroke 2006;37:922-928.
 
40. Brandt T, von Kummer R, Muller-Kuppers M, et al. Thrombolytic therapy of acute basilar artery occlusion. Variables affecting recanalization and outcome. Stroke 1996;27:875-881.
 
41. Zeumer H, Hacke W, Ringelstein EB. Local intraarterial thrombolysis in vertebrobasilar thromboembolic disease. AJNR Am J Neuroradiol 1983;4:401-404.
 
42. Schellinger PD, Hacke W. Intra-arterial thrombolysis is the treatment of choice for basilar thrombosis: pro. Stroke 2006;37:2436-2437.
 
43. Voetsch B, DeWitt LD, Pessin MS, et al. Basilar artery occlusive disease in the New England Medical Center Posterior Circulation Registry. Arch Neurol 2004;61:496-504.
 
44. Kim HY, Chung CS, Moon SY, et al. Complete nonvisualization of basilar artery on MR angiography in patients with vertebrobasilar ischemic stroke: favorable outcome factors. Cerebrovasc Dis 2004;18:269-276.
 
45. Schonewille WJ, Algra A, Serena J, et al. Outcome in patients with basilar artery occlusion treated conventionally. J Neurol Neurosurg Psychiatry 2005;76:1238-1241.
 
46. Devuyst G, Bogousslavsky J, Meuli R, et al. Stroke or transient ischemic attacks with basilar artery stenosis or occlusion: clinical patterns and outcome. Arch Neurol 2002;59:567-573.
 
47. Schonewille WJ, Wijman CA, Michel P, et al. Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study. Lancet Neurol 2009;8:724-730.
 
48. Macleod MR, Davis SM, Mitchell PJ, et al. Results of a multicentre, randomised controlled trial of intra-arterial urokinase in the treatment of acute posterior circulation ischaemic stroke. Cerebrovasc Dis 2005;20:12-17.
 
49. Nogueira RG, Smith WS. Safety and efficacy of endovascular thrombectomy in patients with abnormal hemostasis: pooled analysis of the MERCI and multi MERCI trials. Stroke 2009;40:516-522.