Endovascular therapy was not superior to medical care in patients treated within eight hours of experiencing an ischemic stroke, according the MR RESCUE trial results. Nor did the use of pretreatment CT or MRI identify patients who might be better served with endovascular therapy.
The results were published online Feb. 8 in the New England Journal of Medicine and presented simultaneously at the American Stroke Association’s International Stroke Conference in Honolulu.
Standard medical care calls for tissue plasminogen activator (tPA) to be administered within three to 4.5 hours of onset of symptoms of ischemic stroke. Yet recanalization rates differ by vessel site, with low rates seen in the intracranial internal carotid artery (Stroke 2007;38:967-973). While endovascular therapies have been shown to have higher rates of recanalization, no trial comparing them with standard medical care has been completed, wrote Chelsea S. Kidwell, MD, director of the Stroke Center at Georgetown University in Washington, D.C., and colleagues. They hypothesized that brain imaging to identify ischemic penumbra—areas of ischemia but not infarction—in patients who have exceeded the three hour tPA treatment window would offer benefits as well.
“The use of multimodal CT or MRI to identify patients with a favorable penumbral imaging pattern has been suggested to be particularly helpful in late time windows, when the proportion of patients with penumbral tissue steadily decreases over time,” they wrote. “The hypothesis regarding penumbral-imaging selection presumes that some patients have substantial regions of salvageable brain tissue within several hours after a stroke, and it is this group of patients who would benefit from reperfusion treatments, whereas patients with nonpenumbral patterns (i.e., large core or small or absent penumbra) would not benefit and could even be harmed by reperfusion.”
The MR RESCUE (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy) trial was designed as a randomized, controlled, open-label multicenter study to determine whether penumbral imaging could identify ischemic stroke patients who were likely to benefit from therapies and whether endovascular thrombectomy improved outcomes. The trial was conducted at 22 sites in North America and enrolled patients between 2004 and 2011 with National Institutes of Health Stroke Scale scores of 6 to 29 and a large-vessel, anterior-circulation ischemic stroke.
Patients were randomized within eight hours after the onset of symptoms to undergo either mechanical embolectomy (Merci Retriever or Penumbra System, Concentric Medical) or standard medical care. Patients also underwent pretreatment CT imaging or MRI and were then stratified to either those with penumbral pattern who underwent embolectomy (34 patients); nonpenumbral pattern who underwent embolectomy (30 patients); penumbral pattern who received standard care (34 patients); and nonpenumbral pattern who received standard care (20 patients). Favorable penumbral pattern was defined as substantial salvageable tissue and small infarct core and a nonpenumbral pattern as large core or small or absent penumbra. They used the 90-day modified Rankin scale to assess outcomes.
Demographic and risk factor characteristics were similar between the groups. Patients had a mean age of 65.5 years and a mean time to enrollment of 5.5 hours. A favorable penumbral pattern was detected in 58 percent of the patients and revascularization in the embolectomy group was achieved in 67 percent of the patients. Across the patient cohort, 90-day mortality was 21 percent and the rate of symptomatic intracranial hemorrhage was 4 percent.
Overall results were neutral. Mean scores on the modified Rankin scale did not differ by therapy, with a score of 3.9 for both embolectomy and standard care. Embolectomy compared with standard care in patients with a favorable penumbral pattern was a mean score of 3.9 vs. 3.4, respectively, and 4 vs. 4.4 for nonpenumbral pattern.
Kidwell et al found no difference based on treatment assignment in final infarct volume or lesion growth, and at seven-day imaging there was no significant difference in the rate of reperfusion or recanalization across all four groups.
“[A]mong all enrolled patients regardless of penumbral-imaging pattern on study entry, no significant differences were noted in clinical and imaging outcomes for patients undergoing embolectomy, as compared with those receiving standard medical care,” the researchers wrote.
They suggested that a relatively low rate in revascularization in the embolectomy group may be due the use of first-generation devices. “It is possible that these newer-generation devices would show a treatment benefit (and a benefit in patients with a favorable penumbral pattern) because of both higher recanalization rates and lower complication rates,” they continued. Other factors that may have influenced results were time from imaging to embolectomy, the use of tPA in some patients in the standard care group and possible differences in CT and MRI predictive models.
The eight-year study spanned a period when techniques and practices were changing, they listed among limitations, and they used automated image-analysis software whose real-time analysis “was only modestly successful.” They also noted the challenges of completing a clinical trial given the “lack of equipoise in the stroke community regarding the putative benefits on clinical outcomes of embolectomy versus standard medical care.”
They recommended further randomized trials using newer-generation devices to test the imaging-selection hypothesis and the clinical efficacy of embolectomy compared with standard medical care.