New Hope for Better Post Thrombectomy With IA Tenecteplase

Administering intra-arterial (IA) tenecteplase (TNK) after successful reperfusion by mechanical thrombectomy is safe and leads to better functional outcomes than standard medical management in patients with an anterior circulationlarge vessel occlusion (LVO) stroke, early results of a new study show.

Adding IA TNK “increases the proportion of these patients who actually do well,” study investigator Xiaochuan Huo, MD, PhD, director of the neurological disease center at Beijing Anzhen Hospital in China, told Medscape Medical News. 

It appears the effects of the clot-busting drug “become additive, over and above thrombectomy. It’s pushing the boundary further in how well thrombectomy could help our patients,” Huo added. 

The findings were presented on February 7 at the International Stroke Conference 2025.

Toward Better Outcomes

Research indicates that patients who experience a stroke due to an LVO often have poor outcomes. Even after successful recanalization with endovascular thrombectomy (EVT), up to half of these patients still face unfavorable prognoses. 

This may be attributed to patient comorbidities, poststroke medical complications, or persistent impairment in the flow of the previously occluded vessel. As Huo noted, endovascular treatment may not effectively restore blood flow in smaller vessels and the microcirculation.

As a result, researchers have pivoted to post-reperfusion therapies in a bid to further improve patient outcomes.

The IIb Chemical Optimization of Cerebral Embolectomy (CHOICE) trial showed patients randomly assigned to IA alteplase after EVT had a higher likelihood of 90-day excellent functional outcomes (modified Rankin Score [mRS], 0-1) than those who received placebo (59% vs 40%; adjusted risk difference, 18.4%; 95% CI, 0.3-36.4%; P = .047 ).

However, the CHOICE trial was terminated early because of lack of placebo supply and the ability to maintain the enrolment rate.

Huo noted that there has never been a direct comparison between IA alteplase and IA TNK in the context of postthrombectomy treatment for stroke patients.

The current phase III study, IA rhTNK-tPA Thrombolysis for Acute LVO After Successful Mechanical Thrombectomy Recanalization (ANGEL-TNK), includes 255 adults with a mean age of approximately 72 years, most of whom had a cardioembolic stroke.

Conducted across 19 centers in China, the study enrolled patients who achieved successful reperfusion — defined as eTICI 2b50 to 3 —and had a National Institutes of Health Stroke Scale score of ≥ 2.

Researchers randomly assigned participants to receive standard medical management, which varied depending on various factors, or to also receive recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) by IA thrombolysis between 4.5 and 24 hours from stroke onset.

Huo noted the study excluded patients who had IV thrombolysis (IVT) on admission as Chinese guidelines on the management of stroke don’t extend the time window of IVT beyond 4.5 hours.

Choosing TNK

Researchers selected TNK over alteplase due to its higher fibrin specificity, favorable safety profile, and superior recanalization rates than alteplase.

Since the optimal dose of TNK for IA thrombolysis remains unknown, experts recommended using half the standard intravenous dose — 0.125 mg/kg, with a maximum dose of 12.5 mg.

The primary efficacy outcome of ANGEL-TNK was achieving an excellent 90-day outcome (mRS, 0-1). A greater proportion of patients in the intervention group achieved this outcome than those receiving standard medical treatment (40.5% vs 26.4%; treatment effect, 1.44; 95% CI, 1.06-1.95; P = .02).

Notably, the incidence of symptomatic intracranial hemorrhage within 48 hours of treatment was not higher in the intervention group. Rates were 5.6% in the IV TNK group and 6.2% in the standard medical management group (P = .92).

Ninety-day mortality was similar between the two groups: 21.4% with IA TNK and 21.7% with medical treatment (P = .39). Huo said his team plans to follow study participants to assess 1-year outcomes. 

Guideline Changes Ahead?

The study findings could potentially lead to changes in treatment guidelines for stroke survivors following successful clot removal, Huo said in an American Heart Association (AHA) press release.

“We still need to conduct a direct analysis of individual participant data from this and other trials — an individual patient-level meta-analysis — to establish a robust, evidence-based recommendation,” he added.

The study had several limitations, including its open-label design and no placebo control. In addition, patients who had received periprocedural heparin, antiplatelets, or intravenous thrombolysis were excluded, which may limit the generalizability of the findings.

Furthermore, the trial was conducted among Chinese patients, a population with a high prevalence of intracranial artery stenosis, which could affect the applicability of the results to other groups.

Huo also noted that the IA TNK dose was based on previous clinical experience, and whether lower doses are as beneficial still needs to be studied

Encouraging Results

Commenting on the research for Medscape Medical News, Koto Ishida, MD, neurologist at NYU Langone and professor of neurology at NYU Grossman School of Medicine, New York, said “it’s always exciting” to have a positive stroke trial, especially one that supports an adjunctive treatment, in this case, IA TNK after endovascular therapy. 

One reason this approach resulted in improved clinical outcomes, without an increase in symptomatic hemorrhage, “is that the additional lytic medication helps recanalize smaller vessels distal to the primary occlusion,” said Ishida, who is also a member of the AHA Stroke Systems of Care Advisory Group.

Any effective treatment during an extended time window, in this case 4.5-24.0 hours from stroke onset, is also “particularly encouraging,” said Ishida. “It allows us to help more people hopefully with treatments that are even more effective.”

The study received funding from China Shijiazhuang Pharmaceutical Company (CSPC) Recomgen Pharmaceutical (Guangzhou) Co Ltd.