Although not quite meeting its primary endpoint, a new trial (TESLA) has added to evidence suggesting that patients with large ischemic strokes who have a significant amount of brain tissue damage may still benefit from thrombectomy.
And a new meta-analysis (MAGNA) of previous studies in a similar population has provided more detailed estimates of the treatment benefit of thrombectomy in these patients.
The TESLA trial, which included patients with large core infarcts (ASPECTS score 2-5) within 24 hours of symptom onset, showed encouraging trends towards a benefit with thrombectomy for the primary outcome of 90-day utility-weighted scores on the modified Rankin scale (mRS), but this did not reach the pre-specified Bayesian superiority threshold.
Several secondary efficacy endpoints also showed suggestions of benefits with thrombectomy.
"The interventional group had higher mean or average utility-weighted mRS scores than the control group which means that their functional recovery at 90 days was trending for better outcome and less disability," lead TESLA investigator, Osama Zaidat, MD, Neuroscience & Stroke Director at Mercy St. Vincent Medical Center, Toledo, Ohio, told theheart.org | Medscape Cardiology. "They also showed better neurological improvement and a higher chance of achieving a good outcome (mRS 0-3)."
These patients with large core infarct strokes were not included in the initial trials of endovascular therapy in patients presenting in the late time window, up to 24 hours, as it was thought they would not benefit. However, three recent trials (RESCUE-Japan LIMIT; ANGEL ASPECT; and SELECT 2) have shown that patients with large core infarcts can still benefit from endovascular thrombectomy.
While these three previous trials used sophisticated imaging techniques (MRI or CT perfusion) to select patients, and restricted patients included to those with an ASPECTS score of 3-5, the TESLA study had a more pragmatic design, using just non-contrast CT scan evaluation without advanced imaging to select patients, and extending the inclusion criteria to patients with an ASPECTS score of 2.
"Non-contrast CT scans are available at all stroke centers so this study is more practical, highly generalizable, and more applicable globally," Zaidat commented.
"However, our results suggest that when using non-contrast CT only to select patients, the gain or treatment effect of thrombectomy seems to be smaller than when using sophisticated advanced imaging to make the decision to go for thrombectomy or not as in the other trials," he added.
The TESLA trial results were presented at the recent European Stroke Organisation Conference, held in Munich, Germany.
The study included 300 stroke patients with anterior circulation large‐vessel occlusion (NIHSS of 6 or more) with a large‐core infarction (investigator read ASPECTS Score 2-5), selected on the basis of non-contrast CT scan, who were randomized to undergo intra-arterial thrombectomy or best medical management (control) up to 24 hours from last known well.
The trial had a Bayesian probabilities design, with a primary endpoint of the 90-day utility-weighted mRS (uw-mRS), a relatively new patient-centered outcome used in stroke trials, which includes a quality-of-life measurement. Utilities represent preferences for mRS health states and range from 0 (death) to 1 (perfect health), so in contrast to the traditional mRS scores, a higher uw-mRS score is better.
The 90-day uw-MRS scores were 2.93 in the thrombectomy group vs 2.27 in the control group.
The Bayesian probability of thrombectomy superiority was 0.957, which Zaidat said was "similar" to a P value of .043, but this was less than the prespecified superiority probability of > .975 to declare efficacy.
A separate analysis in a population of patients selected by core-lab read non-contrast CT scan, showed a Bayesian probability of benefit with thrombectomy of 0.98, "similar" to one-sided P value of .02.
In terms of secondary endpoints, there were also some encouraging trends, including a suggestion of benefit in the 90-day mRS ordinal shift (odds ratio 1.40; P = .06).
The number of patients achieving functional independence (mRS 0-2) was 14% in the thrombectomy groups vs 9% in the control group (P = .09); and a good functional outcome (mRS 0-3) was achieved in 30% of thrombectomy patients vs 20% of those in the control group (P = .03).
Major neurological improvement (NIHSS scale of 0-2 or improvement of 8 points or more) occurred in 26% of thrombectomy patients vs 13% of controls (P = .0008).
Quality of life, measured by the EuroQol 5 Dimension 5 Level survey, also showed a trend towards improvement in the thrombectomy group with mean scores of 53 vs 46 (P = .058).
In terms of safety, all-cause mortality was similar in the two groups (35% thrombectomy and 33% control) and symptomatic ICH occurred in 3.97% of thrombectomy vs 1.34% of control patients (relative risk 2.96).
"Cost effective analysis and additional subgroup studies will provide more insight about the training needs to read the CT scan and if there is any value to treat patients with an ASPECTS score of 2," Zaidat concluded.
"Larger pooled analysis will also be very useful in understanding the threshold of brain volume with irreversible damage beyond which thrombectomy wouldn't be helpful," he added.
Meta-Analysis of Previous Studies: MAGNA
Another presentation at the ESOC meeting reported an individual patient data meta-analysis (MAGNA) of the three previous trials suggesting benefit of thrombectomy in patients with large core ischemic strokes of the anterior circulation up to 24 hours of last known well.
The RESCUE Japan Limit trial was conducted in Japan; the SELECT-2 trial in North America, Europe, Australia, and New Zealand; and the ANGEL ASPECT trial in China.
In total, the meta-analysis included 1009 patients, half of whom received thrombectomy and half received medical management only.
Results showed that in the whole population in the three trials, the use of thrombectomy improved functional outcomes, with an adjusted odds ratio (aOR) of 1.78 (P < .001).
Functional independence (mRS 0-2) was also increased (23% vs 9%; adjusted risk ratio [aRR] 2.62; P < .001); as was independent ambulation (mRS 0-3; 41% vs 24%; aRR 1.76; P < .001).
But early neurological worsening was more frequent with thrombectomy (aRR 1.42, 1.09-1.84, P = .010).
No difference in mortality was identified between thrombectomy (27%) and medical management (28%) or in rates of symptomatic ICH (1.8% thrombectomy vs 1.6% medical management).
“The results from the previously published large core trials and from this pooled dataset provide unequivocal evidence on the efficacy and safety of endovascular thrombectomy in patients with large core infarcts," lead author of the MAGNA meta-analysis, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center, affiliate of Case Western Reserve University in Cleveland, Ohio, concluded.
"The benefit persists across the spectrum of age, clinical severity, and time, with clear benefit up to an estimated ischemic core volume of 150 mL," he added. "We have great hopes that these results will lead to more patients being treated and achieving improved functional outcomes."
On how the TESLA results fit in with the previous three trials, Sarraj pointed out to theheart.org | Medscape Cardiology that the TESLA trial was conducted in the US and enrolled patients based on ASPECTS 2-5 on non-contrast CT.
"The primary outcome for intention-to-treat analysis did not reach the pre-specified threshold for efficacy, but the results were largely in the same direction as shown in SELECT2, ANGEL ASPECT, and RESCUE Japan Limit," he said. "These findings further emphasize the efficacy and safety of thrombectomy in patients with large ischemic core, at the same time reinforcing the need to provide results from pooled data from all large core trials."
He noted that results from two further trials of thrombectomy in large core strokes, TENSION and LASTE — both of which have now been stopped early because of the positive findings from the previous studies — are expected soon, and the MAGNA meta-analysis will be updated to include data from all six trials.
"This will increase the accuracy of the estimation of the treatment effect and will give even more power to look further into the details related to subgroups and selection imaging modalities," Sarraj added.
The research team hopes that this joint effort will eventually set the pathway for selection algorithms and treatment boundaries in patients with large vessel occlusion.
TESLA was an investigator-initiated study funded by unrestricted grants from Cerenovus, Penumbra, Medtronic, Stryker, and Genentech. Zaidat is a consultant for Stryker, Cerenovus, Penumbra, and Medtronic.
European Stroke Organisation Conference 2023. Presented May 26, 2023.
Lead image: Puwadol Jaturawutthichai/Dreamstime
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Cite this: More Support for Thrombectomy in Large Core Strokes: TESLA, MAGNA - Medscape - Jun 07, 2023.