Comparative effectiveness of TNK and ALT in acute stroke

25 Feb 2022

In the 2022 International Stroke Conference, Dr. Steven Warach from the University of Texas, Austin, the United States, presented the study conducted by himself and his team on the effectiveness of tenecteplase (TNK) compared with alteplase (ALT) on symptomatic intracranial hemorrhage (sICH) in the setting of acute stroke.1

TNK was developed with a goal to improve the effectiveness and safety of thrombolytic therapy due to its greater fibrin specificity and lower fibrinogen consumption.1 The ASSENT-2 STEMI trial was the largest trial to compare TNK with ALT, and demonstrated fewer non-central nervous system (CNS) bleeds and equal rates of intracranial hemorrhage (ICH) with TNK treatment.1 Other randomized controlled trials comparing these thrombolytic agents in stroke showed superiority in early recanalization of large vessel occlusion (LVO), and a meta-analysis supported a non-inferiority disability-free outcome.1 As a result, the use of TNK becomes more common in clinical practice at various stroke centers.1

In previous trials, the expected ALT sICH rate was 3.7%.1 A total of 6 trials across all TNK doses with a total of 1,005 patients showed a nonsignificant sICH rate of 2.6% with ALT and 2.9% with TNK.1 Moreover, in the subset of patients receiving the most commonly used TNK dose of 0.25mg/kg, the sICH rate was also nonsignificant (ALT 3% vs. TNK 1.9%).1

The study data came from 3 countries, including 25 regions and more than 100 hospitals.1 The sample consisted of consecutive IV thrombolytic cases over a 3-year period (July 2018- June 2021), with most of them receiving TNK at a dose of 0.25mg/kg.1 The primary outcome of sICH was defined as clinical worsening of at least 4 points on the National Institutes of Health Stroke Scale (NIHSS), attributing to parenchymal hematoma, subarachnoid or intraventricular hemorrhage within 36 hours of treatment.1

A total of 7,313 patients were included in the ALT group and 1,925 patients in the TNK group.1 Patients on TNK had a significantly higher age and NIHSS score, a longer onset to needle time, and were more likely to have LVO. All of which increased the risk of sICH.1 The rate of sICH was found to be significantly higher in the ALT arm than in the TNK arm (3.6% vs. 1.8%; p<0.001).1 Additionally, patients in the TNK group who did not undergo mechanical thrombectomy were older with a higher rate of LVO, and showed a significantly lower sICH rate compared with ALT (1.4% vs. 3%, p<0.003).1 Similarly, patients in the TNK who received mechanical thrombectomy were older with a higher NIHSS score and LVO, and demonstrated a significantly lower sICH rate compared with patients in the ALT group (2.4% vs. 5.9%; p<0.001).1

Some limitations of the study included the lack of randomization and blinding, as well as the variability in definition and recording of the registry source data.1 However, it was a multinational, multicenter trial involving a large sample of patients and achieving sICH rates similar to those from the randomized trials.1

In conclusion, sICH was less likely to occur in stroke patients treated with TNK than in patients treated with ALT.1 The differences observed were statistically significant, but have not been previously observed in smaller samples.1 As a result, these data supported the safe use of TNK as an alternative to ALT in clinical practice.1

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