Beyond the big trials, presentations at this year’s International Stroke Conference point to a maturing field that’s under active study.
LOS ANGELES, CA—Three years after the fortunes of mechanical thrombectomy changed for the better based on data presented at the 2015 International Stroke Conference (ISC) in Nashville, TN, the treatment continues to grab headlines.
That year, no fewer than three randomized trials demonstrated that adding the procedure on top of IV thrombolysis can improve functional outcomes in selected patients with acute ischemic strokes caused by large-vessel occlusions. All three had been stopped prematurely after the positive results of the MR CLEAN trial were presented just a few months earlier, and the collective findings caused a paradigm shift in the treatment of these patients. About 5 months after ISC 2015, updated guidelines contained a strong recommendation for use of stent retrievers.
At ISC 2018, held here last week, thrombectomy studies continued to hold a prominent place in the program, headlined by the COMPASS trial, which found that an aspiration-first approach was noninferior to stent retrievers, and the DEFUSE 3 trial, which showed that perfusion imaging can identify patients who will benefit from mechanical thrombectomy up to 16 hours after stroke onset. DEFUSE 3, in combination with the previously reported DAWN trial, made an immediate impact on the guidelines.
Yet these trials weren’t alone. A number of other noteworthy thrombectomy studies were presented at the meeting.
Consistent Effects Across DEFUSE 3 Subgroups
Maarten Lansberg, MD, PhD (Stanford University, CA), presented the DEFUSE 3 results in subgroups defined by age, National Institutes of Health Stroke Scale (NIHSS) score, time from stroke onset, imaging type, and use of general anesthesia.
The treatment effects were generally consistent across subgroups, although the use of general anesthesia instead of conscious sedation appeared to blunt the benefits.
For both age and NIHSS score, the probability of achieving functional independence declined as those measures increased. However, the benefit of endovascular therapy plus medical therapy versus medical therapy alone did not differ across the spectrums of age or NIHSS score.
Patients could qualify for the study based on either MR imaging or CT, and imaging type did not significantly affect the benefits of endovascular therapy.
The trial was designed to assess the impact of mechanical thrombectomy in patients presenting 6 to 16 hours after symptom onset, and Lansberg and his colleagues examined whether there were differences in treatment effects across that span. In fact, the curve was flat, indicating that patients selected on the basis of imaging will derive similar benefits regardless of time to presentation up to 16 hours.
“We certainly don’t want to give the message that it’s okay to delay treatment,” Lansberg said at a press conference. “Time is still critical. What we’re showing, though, is that regardless of where you are along the time spectrum . . . you can still find patients who have salvageable tissue, and if you treat those they’re going to benefit from treatment.”
New-Generation Stent Retriever Performs Well
Osama Zaidat, MD (St. Vincent Medical Center, Toledo, OH), reported results of the ARISE II trial, a single-arm evaluation of a new-generation stent retriever called EmboTrap (Cerenovus), which has not been approved for use in the United States. The trial was designed to obtain 510(k) clearance from the US Food and Drug Administration.
At a press conference, Zaidat noted that currently available stent retrievers are limited in three ways: they fail to achieve successful reperfusion (defined as modified TICI 2b/3 flow) in about 30% of patients, achieve reperfusion using a single pass of the device in only about 25% to 30%, and provide complete or near-complete reperfusion (TICI 2c/3) in only about half of patients.
EmboTrap was designed to overcome some of these limitations and its performance was evaluated in ARISE II, which was conducted at 19 US and European sites. It included 227 patients with large-vessel occlusions in the anterior or posterior circulation who could be treated within 8 hours of symptoms onset.
The primary efficacy outcome was mTICI 2b/3 reperfusion within three passes of the device without use of rescue therapy. This occurred in 80% of patients, with even greater reperfusion (mTICI 2c/3) achieved in 65% within three passes.
A final revascularization outcome of mTICI 2b/3 was seen in 93%, which is comparable to prior thrombectomy trials, Zaidat said. Roughly half of patients (51.5%) achieved mTICI 2b/3 flow in one pass.
Functional outcomes were favorable as well. At 90 days, 67.3% of patients had a modified Rankin Scale (mRS) score of 0 to 2, and 51.6% had a score of 0 to 1. Those rates are among the highest reported in any thrombectomy trials.
For safety, the rate of symptomatic ICH within 24 hours combined with other serious adverse device events was 5.3%. There was no procedure-related mortality, and the 90-day all-cause mortality rate was 9.0%. Both figures are consistent with those seen in prior trials.
A Better Thrombolytic?
The current standard of care for acute ischemic strokes caused by large-vessel occlusions is to give IV thrombolytics to eligible patients before performing mechanical thrombectomy. And there could be room for improvement over the standard alteplase.
Bruce Campbell, MBBS, PhD (University of Melbourne, Parkville, Australia), reported the results of the EXTEND-IA TNK trial, which was conducted at 13 centers in Australia and New Zealand and randomized 204 patients who were scheduled to undergo endovascular therapy and were eligible to receive IV thrombolytics to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase before the procedure.
The primary outcome was the rate of substantial reperfusion (TICI 2b/3 or no retrievable thrombus) at the initial angiogram, and this was higher in patients who received tenecteplase (22% vs 10%), a difference that met criteria for noninferiority (P = 0.002) and superiority (P = 0.02). The number needed to treat with tenecteplase instead of alteplase to avoid one thrombectomy procedure was 9.1.
The distribution of mRS scores at day 90 also favored tenecteplase (common OR 1.7; 95% CI 1.0-2.8), although there was no difference in early neurological recovery by day 3 between trial arms.
There were no safety concerns associated with tenecteplase, and in fact, the mortality rate was nonsignificantly higher with alteplase (18% vs 10%; P = 0.08).
Campbell noted that tenecteplase has greater fibrin specificity and a longer half-life than alteplase, making it suitable for single-bolus administration. That avoids having to transfer patients while they’re receiving an infusion, which is frequently required for patients undergoing mechanical thrombectomy, he said. In addition, tenecteplase typically carries a lower cost.
“Tenecteplase is a very attractive alternative to alteplase prior to thrombectomy,” he said at a press conference.
This story was originally published by TCTMD.com on January 31, 2018.
- Zaidat O. ARISE II clinical trial primary results. Presented at: ISC 2018. January 25, 2018. Los Angeles, CA.
- Lansberg MG. Subgroup analyses of the DEFUSE 3 study. Presented at: ISC 2018. January 25, 2018. Los Angeles, CA.
- Campbell BC. Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): a multicenter, randomized, controlled trial. Presented at: ISC 2018. January 24, 2018. Los Angeles, CA.
- Kamel H, Chung CD, Kone GJ, et al. Medical specialties of clinicians providing mechanical thrombectomy to patients with acute ischemic stroke in the United States. JAMA Neurol. 2018;Epub ahead of print.
- ARISE II was sponsored by Neuravi (now Cerenovus).
- DEFUSE 3 was supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS).
- Zaidat reports serving as a consultant for Neuravi (now Cerenovus).
- Lansberg and Campbell report no relevant conflicts of interest.
- Kamel reports receiving research support from NINDS and the Michael Goldberg Stroke Research Fund