EXTEND-IA: 'Huge' Benefit of Endovascular Therapy for Stroke

February 11, 2015

Nashville, Tennessee — Endovascular therapy with the Solitaire stent retriever improved reperfusion, early neurologic recovery, and functional outcome in patients with ischemic stroke caused by blockage of a proximal cerebral artery in the EXTEND-IA study.

The study was presented here at the International Stroke Conference (ISC) 2015 on February 11 and published simultaneously online in the New England Journal of Medicine.

The Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-arterial (EXTEND-IA) trial, along with two other studies presented at the same ISC session — ESCAPE and SWIFT-PRIME — add to the results of the recently published MR CLEAN trial. All four studies show convincing evidence of benefit for endovascular therapy in selected stroke patients.

The EXTEND-IA investigators, led by Bruce Campbell, MD, Royal Melbourne Hospital, Australia, note that, until recently, trials of endovascular therapy for ischemic stroke have not managed to show a benefit of this approach. But these latest studies have changed that by selecting patients with advanced imaging techniques, using the latest stent retriever devices, and performing the intervention earlier.

"Transforming Outcomes"

"Taken together, these studies will revolutionize the way we treat ischemic stroke caused by a blockage of one of the major cerebral arteries," Dr Campbell commented to Medscape Medical News. Tissue plasminogen activator (tPA) does not work well on its own for this group as the clot is too large to be completely dissolved with thrombolysis, he said. "In our study 40% of patients had a good outcome with tPA alone. This was almost doubled when endovascular therapy was added in."

"This is a huge benefit," he added. "We are talking about transforming the outcome from severe paralysis to patients being able to look after themselves at home for many individuals."

Dr Campbell believes this endovascular therapy will apply to about 10% of all patients with ischemic stroke based on EXTEND-IA enrollment criteria. "But they are the ones who have the greatest potential for disability if untreated."

He estimated that about one third of patients arrive in hospital in time for tPA and about half of these have a major vessel occlusion "After excluding those with too much irreversible tissue damage, we are left with about 10% of patients eligible for endovascular treatment."


EXTEND-IA study planned to randomly assign 100 patients with ischemic stroke within 4.5 hours of symptom onset to tPA alone or tPA plus endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever (Covidien).

All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 mL on computed tomographic (CT) perfusion imaging.

The study was stopped after 70 patients had been enrolled because of significant benefit in the endovascular arm. This was seen in both co-primary endpoints — the percentage of ischemic territory that had undergone reperfusion at 24 hours, and early neurologic improvement (defined as an 8-point or greater reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3).

In addition, the key secondary outcome of a good functional outcome (0 to 2 on the modified Rankin scale [mRS]) was also greatly improved in the endovascular group.

EXTEND-IA Main Results

Endpoint Endovascular + tPA tPA Alone P Value
Median reperfusion at 24 h (%) 100 37 <.001
Early neurologic improvement at 3 d (%) 80 37 .002
mRS score of 0-2 at 90 d (%) 71 40 .01


There were no significant differences in rates of death or symptomatic intracerebral hemorrhage.

Perfusion Imaging to Select Patients

Dr Campbell stressed that a key factor for the success of endovascular treatment is selecting the right patients. "All of these studies are trying to identify patients with minimal irreversible damage to brain tissue, in whom removal of the clot has the potential for real benefit," he said.

He explained that the different trials have used different imaging strategies for this purpose. EXTEND-IA used perfusion imaging with a new automated software program.

While perfusion imaging itself has been around a long time, people find it difficult to use and hard to interpret the results, Dr Campbell said. But his team, in collaboration with researchers at Stanford University, have developed automated software that gives easily accessible information on whether brain tissue is available to be salvaged. Several similar software programs are now commercially available.

The EXTEND-IA trial used CT perfusion imaging to define irreversibly injured brain, and patients who had more than 70 mL of irreversibly damaged tissue were excluded.

Time — Another Key Factor

Another key factor that contributed to the successful result was short time to treatment, Dr Campbell noted.

"Time is always critical in stroke treatment. In our study the use of perfusion imaging took 1 minute to perform, and 5 minutes to interpret," he noted. "Patients underwent a standard CT scan first to confirm an ischemic stroke and then tPA was started. The perfusion imaging was conducted in parallel so not to delay tPA."

In EXTEND-IA the median time from symptom onset to tPA was 136 minutes. The median time from perfusion imaging to start of endovascular therapy (picture to puncture) was 93 minutes, and the median time from symptom onset to groin puncture was 210 minutes.

The EXTEND-IA trial was funded by the Australian National Health and Medical Research Council.

International Stroke Conference (ISC) 2015. Abstract LB2. Presented February 11, 2015.

N Engl J Med. Published online February 11, 2015. Abstract


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.