MR RESCUE: More Bad News for Endovascular Stroke Therapy


Penumbral imaging does not help identify patients who would benefit from endovascular therapy following acute ischemic stroke, according to findings presented February 8, 2013, at the International Stroke Conference in Honolulu, HI. Results from the MR RESCUE trial, which were simultaneously published online ahead of print in the New England Journal of Medicine, also suggest that compared with standard care, endovascular therapy offers no additional benefit.

For MR RESCUE (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy), investigators led by Chelsea S. Kidwell, MD, of Georgetown University (Washington, DC), randomized 127 patients with large-vessel, anterior-circulation stroke to endovascular therapy with mechanical embolectomy (n = 70) or standard medical care (n = 57) within 8 hours of symptom onset from 2004 to 2011. Patients underwent either pretreatment CT or MRI, which permitted stratification by a favorable penumbral pattern vs. a nonpenumbral pattern.

After IMS III and SYNTHESIS Expanded, MR RESCUE represents the third randomized trial in as many days to show no benefit of endovascular therapy compared with standard care in acute stroke patients.

No Differences in Outcomes

Overall, 58% of the 118 eligible patients had a favorable penumbral pattern prior to embolectomy or standard care. There was no interaction between treatment assignment and penumbral pattern (mean difference 0.88; P = 0.14).

For the entire cohort, 90-day functional outcome according to mean modified Rankin Scale score did not differ between the treatment arms. Additionally, in patients with a favorable penumbral pattern, there was no difference in Rankin Scale score between embolectomy and standard care. Furthermore, in patients with a nonpenumbral pattern, embolectomy was not superior (table 1).

Table 1. Ninety-Day Modified Rankin Scale Outcomes

 

Embolectomy
(n = 70)

Standard Care
(n = 57)

P Value

Whole Cohort

3.9

3.9

0.99

Favorable Penumbral Pattern

3.9

3.4

0.23

Nonpenumbral Pattern

4.0

4.4

0.32


After adjustment for age, the only independent prognostic factor, both the interaction (P = 0.43) and treatment-assignment (P = 0.36) analyses remained negative.

The 90-day rates of all-cause mortality, symptomatic hemorrhage, and asymptomatic hemorrhage among the entire cohort were 21%, 4%, and 58%, respectively. These numbers did not differ across groups according to penumbral vs. nonpenumbral pattern or embolectomy vs. standard care.

In a prespecified age-adjusted analysis, 90-day modified Rankin scores were lower in those with a penumbral pattern than in those without (3.6 vs. 4.2; P = 0.047). Treatment assignment alone did not affect final infarct volume or lesion growth. However, final infarct volume was lower overall in those with a favorable penumbral pattern, regardless of treatment assignment. Rates of reperfusion or recanalization were similar irrespective of penumbral pattern or treatment group.

Good clinical outcome and attenuated infarct growth was achieved more often in patients with substantial reperfusion (> 90% reduction in tissue volume from baseline with > 6 second delay in the time to peak of the residue function) and in those with 7-day revascularization (TICI score 2a to 3).

Are First-generation Devices to Blame?

According to the study authors, the lack of difference may be explained in part by a low rate of revascularization in the embolectomy group, perhaps associated with the use of first-generation devices. Embolectomy in MR RESCUE was performed with either the Merci Retriever (Stryker, Kalamazoo, MI) or the Penumbra System (Penumbra, Alameda, CA).

“In randomized trials, newer-generation stent retrievers have had higher revascularization rates and better clinical outcomes than has the Merci Retriever,” Dr. Kidwell and colleagues write. “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.”

The study authors site other factors that may have contributed to the neutral outcome including the extended time from imaging to embolectomy, only some patients in the standard medical care arm receiving IV t-PA, and heterogeneity of the imaging approaches, both CT and MRI.

Yet another possibility, they add, is that the hypothesis that penumbral pattern can be used to predict candidates for endovascular therapy is flawed.

“It is possible that patients with a favorable penumbral pattern, particularly in late time windows [of 3 hours or more] may have a good functional outcome regardless of which recanalization treatment they undergo,” the authors write.

Room for Exploration

In an editorial accompanying the study, Marc I. Chimowitz, MD, of the Medical University of South Carolina (Charleston, SC), agreed, saying the results are most likely due to sufficient perfusion through collateral vessels to limit infarct size.

“However, that hypothesis does not explain why only 14% to 23% of patients with a favorable penumbral pattern had a good outcome in MR RESCUE,” he adds. The penumbral pattern may lack specificity as a marker of durable tissue viability (ie, only a subgroup of patients with favorable patterns have ischemic tissue that can recover with later reperfusion), or the medical group in MR RESCUE may have simply had a higher-than-expected rate of revascularization, Dr. Chimowitz suggested.

Overall, he said that the results “[do not] support the use of endovascular treatment in patients with an ischemic penumbra of any size.” Given that the study is the first of its kind to test the ischemic-penumbra hypothesis, “larger randomized trials will be needed to retest this hypothesis with the use of newer devices once the accuracy of perfusion imaging for identifying viable brain tissue has been more clearly established.”

But the best chance for endovascular therapy to prove itself may be for Medicare to put a moratorium on reimbursement of endovascular treatment for acute ischemic stroke outside of randomized trials, Dr. Chimowitz stressed.

 


Sources:
1. Kidwell CS, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013;Epub ahead of print.

2. Chimowitz MI. Endovascular treatment for acute ischemic stroke—Still unproven. N Engl J Med. 2013;Epub ahead of print.

 

 

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Disclosures
  • The study was supported by a grant from the National Institute of Neurological Disorders and Stroke.
  • Dr. Kidwell reports serving as a consultant to Embrella and Simcere.
  • Dr. Chimowitz reports conflicts of interest with Paraxel/Merck and W.L. Gore and Associates.

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