Endovascular treatment of Stroke: Historical Perspective

John P. Deveikis, MD

Professor Department of Neurosurgery and Radiology University of Alabama at Birmingham Birmingham, AL, USA; Tel. 205-975-9240; E-mail: jdeveikis@uabmc.edu

Effective acute ischemic stroke therapy hinges on rapid restoration of blood flow to the ischemic tissue. Since the National Institute of Neurological Diseases and Stroke r-tPA study,¹ intravenous fibrinolytic therapy in appropriately selected patients has been the primary method used to open the vessels and improve neurological outcome from stroke. The intravenous administration allowed for widespread dissemination of the technique, since therapy could be started very rapidly after the diagnosis is made. However, successful treatment with r-tPA requires careful patient selection and adherence to strict inclusion and exclusion criteria. As a result, there is a significant number of patients who could not receive the therapy. Even though significantly better than placebo for most stroke patients, some still suffered a poor outcome in spite of therapy. This raised the question whether there could be a way to directly apply the fibrinolytic agent to the occlusive thrombus with catheter-based techniques in an effort to more effectively treat large vessel occlusions. Intra-arterial thrombolysis was reported helpful in restoring flow in relatively small series of patients, especially situations like basilar thrombosis, with a dire natural history.² However, only one study, the PROACT study showed a positive impact on neurological outcome compared to placebo.³ Results of this study were often used to justify endovascular treatment of patients ineligible or unresponsive to intravenous r-tPA but intra-arterial administration of the fibrinolytic was often unsuccessful restoring flow in the occluded vessel, and not infrequently was associated with hemorrhagic transformation of the stroke. The endovascular armamentarium increased in the early years of the 21st century with the development of the MERCI device (Stryker, Fremont, CA, USA), a cork-screw-like device designed to mechanically retrieve thrombus.^4,5 This resulted in a higher success rate in opening occluded vessels compared to pharmacological methods and could be used in patients in whom r-tPA is contraindicated. In the years that followed, additional mechanical thrombectomy devices were introduced including stent-like retrievers like the Solitaire (ev3-Medtronic, Irvine, CA, USA), and the Trevo (Stryker, Fremont, CA, USA), and the Penumbra aspiration system (Penumbra, San Leandro, CA, USA) which all appeared to be far more effective than Merci in opening occluded vessels. The IMS III study sought to provide evidence of the effectiveness of endovascular techniques plus intravenous r-tPA versus intravenous r-tPA alone, but it enrolled patients when these newer devices were just becoming available. Most endovascular patients were only treated with intra-arterial r-tPA and, not surprisingly, the study showed no benefit in outcome.⁶ This prompted some to predict the death of endovascular stroke therapy. A short time later, results of well-designed studies beginning with the MR CLEAN study⁷ appeared in rapid succession showing significantly improved outcome with endovascular treatment of large vessel occlusions using the modern stent-like retrievers.^8,9,10,11 Within a short period of time, endovascular therapy went from being on the verge of extinction to being an integral part of comprehensive stroke care. The future will no doubt see investigations refining patient selection criteria, evaluating the role of advanced imaging techniques, evolving and improving the devices and techniques and improving infrastructure to allow all appropriate patients have access to these devices and the trained physicians that can use them safely and effectively.

1. 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.

2. Hacke W, Zeumer H, Ferbert A, Bruckmann H, del Zoppo GJ. Intra-arterial thrombolytic therapy improves outcome in patients with acute vertebrobasilar occlusive disease. Stroke. 1988; 19: 1216-1222. doi: 10.1161/01.STR.19.10.1216

3. 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. 1998; 29: 4-11. doi: 10.1161/01.STR.29.1.4

4. Smith WS, Sung G, Starkman S, et al. Safety and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke: Results of the MERCI Trial. Stroke. 2005; 36: 1432-1438. doi: 10.1161/01.STR.0000171066.25248.1d

5. Smith WS. Safety of mechanical thrombectomy and intravenous tissue plasminogen activator in acute ischemic stroke. Results of the multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trial, part I. AJNR Am J Neuroradiol. 2006; 27: 1177-1182.

6. 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. doi: 10.1056/NEJMoa1214300

7. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015; 372: 11-20. doi: 10.1056/NEJMoa1411587

8. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015; 372: 1019-1030.

9. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015; 372: 2285-2295. doi: 10.1056/NEJMoa1414905

10. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015; 372: 1009-1018. doi: 10.1056/NEJMoa1414792

11. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015; 372: 2296-2306. doi: 10.1056/NEJMoa1503780