Endovascular Treatment Shows Dramatic Benefits for Large Strokes in 3 Trials

Three trials presented February 11, 2015, at the International Stroke Conference in Nashville, TN—ESCAPE, EXTEND-IA, and SWIFT PRIME—have shown that for acute ischemic stroke caused by large proximal intracranial occlusions, mechanical thrombectomy plus IV thrombolysis improves reperfusion and functional outcomes compared with IV thrombolysis alone. ESCAPE and EXTEND-IA also were published simultaneously online in the New England Journal of Medicine.

All 3 trials were halted prematurely following presentation late last year of the MR CLEAN trial, which found that adding endovascular therapy—intraarterial thrombolysis, mechanical treatment, or both—improved reperfusion and functional outcomes vs IV thrombolysis alone. Taken together, these 4 trials stand in sharp contrast to the negative results of the IMS III, MR RESCUE, and SYNTHESIS Expansion trials, all published in NEJM in February 2013.

The new findings “provide definitive, overwhelming evidence that in select patients who have large strokes and have received intravenous [tissue plasminogen activator (tPA)] but have a low likelihood of having the arteries opened with tPA alone, the use of these new catheters in a very well-coordinated, time-efficient way can improve outcomes dramatically,” Lee H. Schwamm, MD, of Massachusetts General Hospital Institute for Heart, Vascular and Stroke Care (Boston, MA), told TCTMD in a telephone interview.

“It’s a watershed moment in the field,” he said.


Bruce C.V. Campbell, MBBS, PhD, of Royal Melbourne Hospital (Parkville, Australia), reported the results of the EXTEND-IA trial, which was stopped early after enrolling 70 patients at 14 centers in Australia and New Zealand. All had occlusion of the internal carotid or middle cerebral artery, evidence of salvageable brain tissue, and an ischemic core less than 70 mL on CT perfusion imaging. Patients received 0.9 mg tPA per kg of body weight within 4.5 hours of symptom onset before being randomized to thrombectomy with the Solitaire FR stent retriever (Covidien) within 6 hours of onset or continued IV thrombolysis.

Endovascular therapy was initiated at a median of 210 minutes after stroke onset, and the median interval between confirmatory imaging and thrombectomy was 93 minutes.

Coprimary outcomes were the percentage of ischemic territory that had undergone reperfusion at 24 hours and the percentage of patients with early neurologic improvement, defined as at least an 8-point reduction in the NIH Stroke Scale (NIHSS) score or a score of 0-1 on day 3. Both outcomes, in addition to the proportion of patients with functional independence (modified Rankin Scale [mRS] score of 0 to 2) at 90 days, favored endovascular therapy (table 1). Rates of death and symptomatic intracerebral hemorrhage did not differ between the groups.

Table 1. EXTEND-IA Outcomes



(n = 35)

IV tPA Alone

(n = 35)

P Value

Reperfusion at 24 Hours, median



< .001

Early Neurologic Improvement at 3 Days




Functional Independence at 90 Days








Symptomatic Intracerebral Hemorrhage




Complications of the thrombectomy procedure included 1 wire perforation and 2 cases of embolization into a different vascular territory.


Michael D. Hill, MD, MSc, of Foothills Medical Center (Calgary, Canada), reported results from the ESCAPE trial, which included 316 patients with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation on both noncontrast CT and CT angiography who were enrolled at 22 centers in Canada, the United States, Europe, and South Korea. They were randomized to standard care or standard care plus endovascular treatment with available thrombectomy devices (retrievable stents in 86.1%). Overall, 238 patients received IV tPA.

The protocol called for a target of 90 minutes for the time from head CT to reperfusion, and the median time achieved was 84 minutes.

The primary outcome was a shift in mRS score at 90 days, measured using a common OR (indicating the likelihood of improving 1 point). Favoring endovascular therapy, the study found a common OR of 2.6 (95% CI 1.7-3.8).

Some secondary outcomes, including the percentage of patients who were functionally independent (mRS 0-2) at 90 days, had an NIHSS score of 0-2 at 90 days, and had a Barthel Index score of 95-100 at 90 days, also supported the use of thrombectomy (table 2).

Table 2. ESCAPE Outcomes


Endovascular + Standard Care

(n = 165)

Standard Care

(n = 150)

P Value

Functional Independence at 90 Days



< .001

NIHSS 0-2 at 90 Days



< .05

Barthel Index Score 95-100 at 90 Days



< .05





Symptomatic Intracerebral Hemorrhage




Findings were consistent across various subgroups.


Jeffrey Saver, MD, of the UCLA Comprehensive Stroke Center (Los Angeles, CA), presented the primary results of the SWIFT PRIME trial, which included 196 of an expected 477 patients enrolled at 39 US and European centers when enrollment was halted last November. The patients had large vessel occlusions in the intracranial internal carotid artery, the M1 segment of the middle cerebral artery, or the carotid terminus confirmed by CT or magnetic resonance angiography and were eligible for IV tPA within 4.5 hours and mechanical clot removal within 6 hours of stroke onset. Thrombectomy was performed with the Solitaire FR or Solitaire 2 (also Covidien) devices.

Median time from qualifying imaging to groin puncture was 58 minutes, from imaging to first deployment was 87 minutes, and from stroke onset to first deployment was 252 minutes.

Distribution of mRS scores at 90 days (primary outcome) showed a benefit for the addition of thrombectomy versus IV tPA alone (P = .0002). The rate of functional independence at that time point was 60.2% with endovascular treatment and 35.5% without (OR 2.75; 95% CI 1.53-4.95), a finding consistent across subgroups.

Dr. Saver and his colleagues calculated that for every 100 patients treated, 39 would have a better 3-month outcome with thrombectomy than with IV tPA alone, with an additional 25 achieving functional independence.

Improvement in NIHSS score at 27 hours was greater in the endovascular arm (8.5 vs 3.9 points; P < .0001). There were no differences in rates of death at 90 days (9.2% vs 12.4%; P = .50), any serious adverse event (35.7% vs 30.9%; P = .54), or symptomatic intracerebral hemorrhage (1.0% vs 4.1%; P = .21).

Techniques, Processes Evolve From Older Trials

The sudden influx of positive trials of endovascular therapy in acute ischemic stroke can be explained by the use of a better approach to imaging for selecting patients; faster treatment; and superior, next-generation thrombectomy devices, according to Dr. Schwamm, who is a spokesperson for the American Heart Association/American Stroke Association.

The combination of those factors is key, he said, and simply using the new devices without the other enhancements likely would not yield the benefits observed in these trials. The CT-based imaging techniques employed are not as advanced as the magnetic resonance-based methods used in the older trials, he added, but they are good enough to select the patients who have large occlusions and enough salvageable brain tissue to make intervention worthwhile.

The faster treatment, both with IV tPA and thrombectomy, achieved in the new trials was also important, Dr. Schwamm said, adding that emphasis on reducing door-to-tPA times in recent years paved the way for more efficient delivery of endovascular therapies. Time to treatment also dropped because of the use of less complex CT-based imaging, which does not take as long as MR-based imaging, he said.

Widespread Adoption of Thrombectomy Expected

Dr. Schwamm predicted that techniques from these trials will disseminate rapidly within the stroke community, as many centers in the United States are already equipped to use them. However, there is a need for more interventionalists trained to perform thrombectomy and teams tasked with supporting more efficient delivery of the procedure.

“It’s going to take some time to teach and get teams across the world to be operating with this kind of efficiency,” Dr. Hill noted in a telephone interview with TCTMD. “Nevertheless, it is possible. There are people in place who have the skills to do this.”

Triage of stroke patients needs to be retooled, with an eye on individual systems, geography, and available resources, he added. “In order to achieve the speed, we have to get the right patients, with the right deficit, to the right hospital, with the right people, and the right team to get these same outcomes.”

According to Dr. Schwamm, however, caution is warranted to ensure that the results of these trials are not oversold. He pointed to the continued importance of rapid and appropriate administration of tPA, even in patients who will eventually require thrombectomy.

“The message very clearly is that if you’re eligible for tPA, start tPA,” he said. “If you start tPA and you have a big blockage of a proximal artery and the brain parenchyma still look preserved, then you launch the patient into the cath lab.”



1. Campbell BCV, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;Epub ahead of print.
2. Goyal M, Demchuck AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;Epub ahead of print.
3. Saver J. Primary results: Solitaire FR With the Intention For Thrombectomy as PRIMary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME). Presented at: International Stroke Conference; February 11, 2015; Nashville, TN. 


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Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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  • EXTEND-IA was funded by the National Health and Medical Research Council of Australia, the National Heart Foundation of Australia, the Royal Australasian College of Physicians, and Royal Melbourne Hospital Home Lottery Grants. Covidien supplied the Solitaire FR device and supported the trial infrastructure with an unrestricted grant.
  • ESCAPE was funded by Covidien.
  • Dr. Campbell reports receiving grants from Covidien, the National Health and Medical Research Council of Australia, the National Heart Foundation of Australia, the Royal Australasian College of Physicians, and the Royal Melbourne Hospital Home Lottery as well as additional nonfinancial support from Covidien related to the trial.
  • Dr. Hill reports receiving grants from Alberta Innovates Health Solutions, the Calgary Stroke Program, Covidien, the Heart &amp; Stroke Foundation of Alberta, the Hotchkiss Brain Institute, and the University of Calgary; nonfinancial support from Alberta Health Services and Hoffmann-La Roche Canada; and personal fees from Merck. He also reports having a pending patent related to triaging acute stroke patients and owning stock in Calgary Scientific, a company focused on medical imaging software.
  • Dr. Saver reports serving as a consultant to Covidien.
  • Dr. Schwamm reports serving on the data and safety monitoring board for a trial of a thrombectomy device from Penumbra.