AT THE INTERNATIONAL STROKE CONFERENCE
NASHVILLE, TENN. (FRONTLINE MEDICAL NEWS) – Treatment of selected patients with acute ischemic stroke underwent a dramatic, sudden shift with reports from three randomized, controlled trials that showed substantial added benefit and no incremental risk with the use of catheter-based embolic retrieval to open blocked intracerebral arteries when performed on top of standard thrombolytic therapy.
The three studies, each run independently and based in different countries, supported the results first reported last October and published online in December ( N. Engl. J. Med. 2015;372:11-20 ) from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) study. These were the first contemporary trial results to show a jump in functional outcomes with use of a stent retriever catheter to pluck out the occluding embolus from an artery in the stroke patient’s brain to restore normal blood flow.
All three of the newly-reported studies stopped before reaching their prespecified enrollment levels because of overwhelming evidence for embolectomy’s incremental efficacy.
With four reports from prospective, randomized trials showing similar benefits and no added harm to patients, experts at the International Stroke Conference uniformly anointed catheter-based embolectomy the new standard of care for the small percentage of acute, ischemic-stroke patients who present with proximal, large-artery obstructions and also match the other strict clinical and imaging inclusion and exclusion criteria used in the studies.
“Starting now, in patients with an acute ischemic stroke due to proximal vessel occlusion, rapid endovascular treatment using a retrieval stent is the standard of care,” Dr. Mayank Goyal declared from the plenary-session podium. He is a professor of diagnostic imaging at the University of Calgary (Canada) and an investigator in two of the three trials presented at the conference, which was sponsored by the American Heart Association.
“Today the world changed. We are now in a new era, the era of highly-effective intravascular recanalization therapy,” said Dr. Jeffrey L. Saver, professor of neurology and director of the Stroke Center at the University of California, Los Angeles, and lead investigator for one of the new studies.
In three of the four studies, the researchers did not report specific numbers on how selective they were in focusing in on the ischemic stroke patients most likely to benefit from this treatment, but the one study that did, EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial), run at nine Australian centers and one in New Zealand, showed the extensive winnowing that occurred. Of 7,796 patients with an acute ischemic stroke who initially presented, 1,044 (13%) were eligible to receive thrombolytic therapy (alteplase in this study). And from among these 1,044 patients, a mere 70 – less than 1% of the initial group – were deemed eligible for randomization into the embolectomy trial. The top three reasons for exclusion of patients who qualified for thrombolytic treatment from the trial was an absence of a major-vessel occlusion (45% of the excluded patients), presentation outside of the times when enrollment personnel were available (22%), and poor premorbid function (16%).
But subgroup analyses in three of the four studies (EXTEND-IA with a total of 70 patients was too small for subgroup analyses) showed no subgroup of patients who failed to benefit from embolectomy, including elderly patients who in some cases were nonagenarians.
The unusual confluence of having four major trials showing remarkably consistent results meant that the stroke experts gathered at the meeting focused their attention not on whether stent retrievers should now be widely and routinely used in appropriate patients but instead on how this technology will roll out worldwide.
“From here on out we are obligated to treat patients with this technology at centers that can do this, and we are obligated to have more centers that can provide it,” said Dr. Kyra J. Becker, professor of neurology and neurological surgery and codirector of the Stroke Center at the University of Washington, Seattle. Dr. Becker had no involvement in any of the stent retriever trials. “I had been a doubter of this technology,” primarily because results reported at the International Stroke Conference a couple of years ago failed to prove the efficacy of clot retrieval in ischemic stroke patients, she noted. “Our ability to select appropriate patients and do it in a timely fashion hadn’t gotten to where it had to be until now,” Dr. Becker said in an interview.
“We only enrolled patients with blockages, we treated them quickly, and we used much better devices to open their arteries,” Dr. Saver added, explaining why the new studies succeeded when earlier studies had not.
The trial led by Dr. Saver, SWIFT-PRIME (SOLITAIRE™ FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), enrolled 195 patients at 39 sites in the United States and in Europe. At 90 days after treatment, 59 patients (60%) among those treated with thrombolysis plus embolectomy had a modified Rankin Scale score of 0-2, compared with 33 patients (36%) among those treated only with thrombolysis (in this trial intravenous treatment with tissue plasminogen activator), a highly significant difference for the study’s primary endpoint.
“For every two and half patients treated, one more patient had a better disability outcome, and for every four patients treated, one more patient was independent at long-term follow-up,” Dr. Saver said. Safety measures were similar among patients in the study’s two arms.
The EXTEND-IA results showed a 90-day modified Rankin Scale score of 0-2 in 52% of the embolectomy patients, compared with 28% of those treated only with thrombolysis. The study’s co–primary endpoints were median level of reperfusion at 24 hours after treatment, 100% with embolectomy and 37% with thrombolysis only, and early neurologic recovery, defined as at least an 8-point drop from the baseline in the National Institutes of Health Stroke Scale score or a score of 0 or 1 when assessed 3 days after treatment. Patients met this second endpoint at an 80% rate with embolectomy and a 37% rate with thrombolysis only. Results of EXTEND-IA appeared in an article published online concurrently with the meeting report ( N. Engl J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414792] ).
The third, and largest, of the three studies presented at the conference, ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), enrolled 316 patients at 11 centers in Canada, 6 in the United States, 3 in South Korea, and 1 in Ireland. After 90 days, 53% of patients in the embolectomy arm had achieved a modified Rankin Scale score of 0-2, this study’s primary endpoint, compared with 29% of patients in the thrombolysis-only arm (treatment with alteplase). These results also appeared in an article published online concurrently with the conference report ( N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905 ]).
SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures.
On Twitter @mitchelzoler
