Endovascular treatment has emerged as the best thing since intravenous tissue plasminogen activator (IV t-PA) for acute ischemic stroke after five recent studies showed positive outcomes. Stent retrievers starred in the trials, with imaging playing a critical supporting role. But in clinical practice, which neuroimaging method best identifies likely beneficiaries is up for debate.
The fab five
It all started with MR CLEAN. MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) found that acute ischemic stroke patients who had proximal intracranial occlusions and received endovascular therapy along with standard care were more likely to achieve functional independence by three months than counterparts randomized to standard care alone (N Engl J Med 2015;237:11-20). The positive results, published in December 2014, prompted interim analyses of several other studies under way that compared endovascular treatment and usual care to usual care alone.
In the beginning: Almost 50% of patients treated with tPA alone in the National Institutes of Neurologic Disorders and Stroke (NINDS) trial had achieved essentially full recovery (N Engl J Med. 1995 Dec 14. 333(24):1581-7). However, subgroup analyses of the NINDS data showed that patients with severe strokes had only an 8% likelihood of achieving clinically significant improvement with tPA (Stroke. 1997 Nov. 28(11):2119-25). The poor outcome in these patients inspired the search for acute-stroke treatments that are more effective than tPA.
Three randomized clinical trials skidded to a halt in enrollment due to efficacy: ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT of Recanalization Times); SWIFT PRIME (Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment); and EXTEND IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial). The Spanish study REVASCAT (Randomized Trial of Revascularization with Solitaire FR Device versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting within Eight Hours of Symptom Onset) stopped recruitment for ethical reasons, based on the findings of these studies.
The trials shared several overarching features. They primarily relied on stent retrievers for endovascular therapy and all required imaging to identify patients with proximal large vessel occlusions who were likely to benefit or not from endovascular treatment. The back-to-back results released over the next few months in favor of endovascular therapy cheered neurologists and catalyzed medical societies to integrate the evidence into practice.
“The American Heart Association decided about January to redo the guidelines because they knew there would be new data,” recalls William J. Powers, MD, chair of the neurology department at the University of North Carolina in Chapel Hill and chair of the writing committee that updated stroke guidelines this year. “The original timeline had them to be published in September but because of the importance of this, it was pushed way up to be done in June.”
The update added several Class I Level of Evidence A recommendations, the top tier in the guideline hierarchy. It supported the use of stent retrievers in patients if they met a number of additional criteria and recommended using swift noninvasive vascular imaging if a physician was considering the use of endovascular therapy. Based on the imaging modalities chosen in the trials, it allowed CT, CT angiography, MR and MR angiography but cautioned that more research was needed to show the benefits of CT perfusion and other advanced imaging.
Learning from the past
It all may have started with MR CLEAN, but with a strong assist from previous studies that fell short of their goal of moving the needle in stroke care. IMS III (Interventional Management of Stroke III), which compared endovascular therapy plus IV tPA to IV tPA alone, was stopped early in 2012 due to futility. The next year, MR RESCUE (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy), a four-arm study designed to identify patients by CT or MR with large areas of salvageable brain tissue and a small infarct core and show they would benefit from endovascular treatment, proved neutral; embolectomy failed to best standard care in patients with or without favorable