Since they didn't talk about 100% recovery it was obviously a failure as survivors would consider it. We can't let our stroke medical 'professionals' continue using the tyranny of low expectations to justify THEIR COMPLETE FAILURE TO GET SURVIVORS RECOVERED!
Intra-Arterial Lytics Find Redemption as Adjuncts to Endovascular Stroke Therapy
IA tenecteplase, alteplase make new inroads after a period of stalled progress
LOS ANGELES -- For patients with large vessel occlusion (LVO) strokes, researchers found ways to make adjunctive intra-arterial (IA) thrombolytics work to improve outcomes after successful endovascular therapy (EVT), according to trials presented here at the International Stroke Conference (ISC).
Going the IA tenecteplase route was the ANGEL-TNK trial, which showed that after successful mechanical thrombectomy within 24 hours of acute ischemic stroke onset, people who went on to receive the thrombolytic drug were more likely to achieve excellent functional outcomes(For survivors the only excellent outcome is 100% recovery! Did this accomplish that?) at 90 days. More good news: this did not come at the cost of excess symptomatic intracranial hemorrhage (sICH) or mortality, reported Xiaochuan Huo, MD, PhD, of Beijing Anzhen Hospital.
That trial came out positive testing an IA tenecteplase dose of 0.125 mg/kg for 15 minutes (maximum 12.5 mg), even though DATE, another study presented at the same session at ISC, identified the lower 0.03125 mg/kg and 0.0625 mg/kg tenecteplase doses as optimal following successful EVT in patients with LVO stroke and small ischemic cores, as reported by Xianhua Hou, MD, of Southwest Hospital of Army Medical University in Chongqing, China.
Separately, in the PEARL trial, researchers revived the concept of IA alteplase after mechanical thrombectomy and saw it also improves patients' likelihood of an excellent outcome at 90 days, according to Raul Nogueira, MD, of University of Pittsburgh, and Yamei Tang, MD, of Sun Yat-sen Memorial Hospital in Guangzhou, China.
The impetus for the three randomized trials presented here is the known inconsistency of clinical outcomes of LVO stroke patients even if they manage successful recanalization with EVT.
Previous attempts to use IA thrombolytics as a strategy to boost outcomes have had mixed results. The CHOICE trial, terminated early but suggestive of benefit from IA alteplase for stroke patients with near-complete or complete reperfusion, was followed by the disappointing and more recent POST-TNK and POST-UK trials, in which adjunctive IA tenecteplase and urokinase, respectively, fell short for helping patients achieve longer survival without disability after EVT.
IA Tenecteplase in ANGEL-TNK
ANGEL-TNK investigators confirmed that a certain kind of EVT patient did benefit from IA tenecteplase after all.
Based on their stroke cohort, excellent modified Rankin Scale (mRS) scores of 0-1 at 90 days were significantly more likely among those randomized to IA tenecteplase over EVT alone (40.5% vs 26.4%, P=0.02). The frequency of brain bleeds in the 2 days after treatment was comparable between groups (5.6% vs 6.2%, P=0.92), as was the number of deaths within 90 days (21.4% vs 21.7%, P=0.39).
ANGEL-TNK had 256 people randomized to adjunctive tenecteplase or EVT alone at 19 centers in China. Participants were all stroke patients who had LVOs in the anterior circulation and were treated from 4.5 hours to 24 hours since they were last seen well -- the median time from stroke onset to randomization being roughly 10-11 hours.
Huo and colleagues had opted for a CHOICE-like study population of people who achieved majority-complete reperfusion (eTICI 2b50-3) after EVT. There were no early IV antiplatelets allowed for the study. Unlike CHOICE, however, ANGEL-TNK uniquely used perfusion imaging and did not allow IV thrombolysis.
The study dose of 0.125 mg/kg was also stronger than POST-TNK's tenecteplase dose of 0.0625 mg/kg.
Trial participants had a median age just over 71 years, with about 55% men. Strokes were typed as cardioembolic in nearly 70% of cases. The patients had a median NIH Stroke Scale score of 15-16 at admission. Occlusion sites were in the M1 segment of the middle cerebral artery nearly half the time, and were less frequently in the internal carotid artery and in middle cerebral artery M2. ASPECTS was a median 7 in both the tenecteplase and control groups. About 80% of people had evidence of some partial collateral filling.
On subgroup analysis, it appeared that people driving the good results with tenecteplase may be those with serum glucose at least 100 mg/dL at admission and those with eTICI 2b instead of 2c/3.
Limitations of ANGEL-TNK include its open-label design and lack of placebo control. There may also be limited generalizability outside the study's Chinese population, known to trend toward more intracranial artery stenosis, and the types of people excluded from the study (e.g., people who got IV thrombolysis or had periprocedural heparin and antiplatelets during their EVT, and people who were disabled before their stroke).
IA Alteplase in PEARL
PEARL marks another attempt to find benefit in IA alteplase after mechanical thrombectomy, almost replicating the dose tested in CHOICE (0.225 mg/kg, maximum 20 mg instead of CHOICE's maximum 22.5 mg).
The results indicated significant benefit in terms of more people enjoying excellent functional outcomes (90-day mRS 0-1 scores of 44.8% with alteplase vs 30.2% with control, P=0.01). However, alteplase's results fell short for showing a significantly better distribution of mRS scores across the cohort as a whole, Tang told the audience here.
As for safety, risks were about the same between study groups when researchers looked at symptomatic ICH at 36 hours (4.3% alteplase vs 5.0%, P=0.67) and all-cause mortality within 90 days (17.1% vs 11.3%, P=0.12).
Results were consistent across subgroups, including by receipt of IV thrombolysis and by eTICI score.
The PEARL trial had been conducted at several dozen Chinese centers around the same time as ANGEL-TNK. Included were 324 people randomized to intra-arterial alteplase or regular medical treatment with mechanical thrombectomy.
Like ANGEL-TNK, the PEARL group sought LVO stroke patients with occlusions in the internal carotid artery and M1 or M2 segments of the middle cerebral artery (MCA), post-EVT reperfusion reaching eTICI 2b50-3, and who were still in the 24-hour window since symptom onset. Similarities end with PEARL's inclusion of people who got IV thrombolysis.
The researchers ended up with a cohort averaging 65.8 years, with 69.4% men. Nearly 42% had had IV thrombolysis before mechanical thrombectomy. Baseline NIH Stroke Scale score was a median 15 and ASPECTS a median 9. People most commonly had cardioembolic strokes, and the occlusion was in the M1 segment of the MCA in 72% of cases. Participants had been randomized roughly 7 hours after stroke onset.
The positive results of PEARL put IA alteplase back on the map after attention had shifted to tenecteplase for its higher fibrin specificity, lower bleeding risk, and longer half-life.
![author['full_name']](https://clf1.medpagetoday.com/media/images/author/nicoleLou_188.jpg)
Disclosures
ANGEL-TNK was funded by grants from CSPC Recomgen Pharmaceutical.
PEARL was funded by grants from Tang's institution and Genesis MedTech.
Huo, Hou, and Tang had no disclosures.
Nogueira disclosed consulting to Stryker, Cerenovus, Medtronic, Microvention, Imperative Care, Route 92, Perfuze, and Phenox; and holding stakes in Viz.AI, Brainomix, Euphrates, Rapid Pulse, and Vesalio.
Primary Source
International Stroke Conference
Source Reference: Huo X, Miao Z "ANGEL-TNK: intra-arterial tenecteplase thrombolysis after successful endovascular therapy" ISC 2025.
Secondary Source
International Stroke Conference
Source Reference: Hou X, et al "The optimal dosage of adjunctive intra-arterial tenecteplase following successful endovascular thrombectomy in patients with large vessel occlusion acute ischemic stroke (DATE) trial" ISC 2025.
Additional Source
International Stroke Conference
Source Reference: Tang Y, et al "Intra-arterial alteplase for acute ischemic stroke after mechanical thrombectomy (PEARL): a multicenter randomized trial" ISC 2025.
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