Endovascular Therapy Bests IV t-PA for Large-Vessel Strokes

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In patients with acute intracranial large-vessel occlusions, endovascular therapy reduces final infarct size more than either intravenous tissue plasminogen activator (IV t-PA) or no reperfusion therapy. The benefit is greatest for those with more-proximal occlusions and more- severe strokes, according to an observational study published online May 13, 2013, ahead of print in JAMA Neurology.

Rishi Gupta, MD, of Emory University (Atlanta, GA) , and colleagues retrospectively examined results of 203 consecutive patients who received endovascular therapy (n = 134), IV t-PA (n = 38), or no reperfusion therapy (n = 31) at 2 large-volume stroke centers—Emory University Hospital and Grady Memorial Hospital—in Atlanta between 2009 and 2011. All had intracranial large-vessel occlusions of the anterior circulation and presented within 360 minutes of the last known normal appearance.

Notably, most endovascular patients (67.9%) also received full-dose IV t-PA prior to their endovascular procedure.

The only baseline difference among the 3 treatment groups was that patients who received no reperfusion tended to have longer intervals before their initial CT scan than those given IV t-PA or endovascular therapy (P = 0.001).

Smaller Infarcts with Endovascular Approach

Final infarct volume was determined using magnetic resonance or computed tomographic imaging within 48 hours of admission. Endovascular therapy resulted in smaller median infarct volume (42 cm³) than either IV t-PA (109 cm³; P = 0.001) or no reperfusion therapy (110 cm³; P = 0.002).

The reduction in infarct volume was greater than with IV t-Pa or no reperfusion regardless of the location of the proximal occlusion (table 1).

Table 1. Final Infarct Volume by Location of Occlusion

Patients presented with a median National Institutes of Health Stroke Scale (NIHSS) score of 19 (interquartile range, 14-23). Endovascular therapy reduced final stroke volume in patients with scores of 14 or higher but not in those with scores of 8 to 13 (table 2). An NIHSS score of at least 14 also was associated with the likelihood of achieving good (P = 0.04) or acceptable (P = 0.002) outcome at discharge according to the modified Rankin Scale.

Table 2. Final Infarct Volume by Stroke Severity

“Our findings can help others to identify the patients most likely to benefit from [intra-arterial therapy] and can provide a basis for designing future clinical trials to assess the efficacy of [such treatment] compared with medical therapy,” the researchers conclude.

Moving Forward

The current study comes on the heels of disappointments for endovascular therapy this spring at the International Stroke Conference 2013, including negative results from MR RESCUE, IMS III, and SYNTHESIS Expanded.

In trying to interpret the evidence, Dr. Gupta told TCTMD in a telephone interview, it is important to remember that “those were all prospective, randomized trials [making] one-to-one comparisons. This is retrospective . . . and [a little bit] exploratory.”

The goal here, he said, was to see if there were any signals identifying which patients would benefit most from endovascular therapy. If such patients were selected when performing randomized trials, Dr. Gupta suggested, researchers might be more apt to see positive results.

Dr. Gupta pointed out that both the location of occlusion and NIHSS scale are easy to ascertain. Approximately 10% to 15% of ischemic stroke patients in the United States have scores of 14 or higher, he estimated.

Outside Source: Interpret Cautiously

In a telephone interview with TCTMD, Joseph P. Broderick, MD, of the University of Cincinnati (Cincinnati, OH), said that while the increased benefit to patients with more proximal and severe strokes is noteworthy, the study’s retrospective design merits careful interpretation.

“The bottom line is that clearly there’s a different way in which patients are triaged and treated [at Emory and Grady] during this time window,” said Dr. Broderick, who served as principal investigator for IMS III. He highlighted fact that patients in the endovascular group received IV t-PA nearly 20 minutes faster than the IV t-PA alone group (P = 0.11), noting that the disparity is big enough to potentially sway outcomes in favor of endovascular therapy.

The majority of patients in the endovascular group (91.8%) were treated at Grady Memorial Hospital, while 75% of the 69 patients in the combined IV t-PA and no reperfusion groups were treated at Emory University Hospital.

Moreover, Dr. Broderick noted, it is difficult to tell for sure whether some patients may have been excluded from analysis because they lacked imaging data or died.

Infarct Size a ‘Reasonable’ Surrogate

A key aspect to the current study, Dr. Gupta noted, is its emphasis on final infarct volume. “The whole purpose of endovascular treatment is to save brain tissue, and measuring final infarct volume at the end really tells you if the treatment works,” he said. “If you save tissue, the treatment has had its intended effect.”

Harold P. Adams Jr, MD, of the University of Iowa (Iowa City, IA), and Michael T. Froehler, MD, PhD, of Vanderbilt University (Nashville, TN), point out in an accompanying editorial that the study deserves credit as one of the first to use final infarct volume as a surrogate marker.

“An association between the volume of infarction on brain imaging and the severity of neurological impairments is well known and thus, the use of computed tomography as a surrogate is reasonable,” they write, agreeing that Dr. Gupta and colleagues provide useful information to guide the direction of future research.

Dr. Broderick also said that final infarct size is an accepted secondary endpoint but described the confidence intervals seen here as “huge.” In short, he said, “[y]ou have evidence of trends for smaller infarcts with the [endovascular] approach.”

Study Details

Endovascular therapy was performed with devices including the Penumbra System (62.7% Penumbra, Alameda, CA), Merci Retriever (41.8%; Stryker, Kalamazoo, MI), and other stent retriever devices (13.4%). Nearly a third of patients (32.0%) received treatment with more than 1 device and 11.9% received only catheter-delivered intra-arterial t-PA.

 

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Sources:
1. Rangaraju S, Owada K, Noorian AR, et al. Comparison of final infarct volumes in patients who received endovascular therapy or intravenous thrombolysis for acute intracranial large-vessel occlusions. JAMA Neurol. 2013;Epub ahead of print.

2. Adams HP, Froehler MT. Emergency management of acute ischemic stroke: The evolving roles of intravenous and endovascular therapy. JAMA Neurol. 2013;Epub ahead of print.

 

 

Related Stories:

• MR RESCUE: More Bad News for Endovascular Stroke Therapy
• IMS III: Endovascular Therapy Fails to Improve Stroke Recovery vs. t-PA Alone
• SYNTHESIS Expanded: Endovascular Treatment No Better Than IV tPA for Acute Stroke