The following is a summary of “Tenecteplase, 0.4 mg/kg, in Moderate and Severe Acute Ischemic Stroke: A Pooled Analysis of NOR‐TEST and NOR‐TEST 2A,” published in the October 2023 issue of Cardiology by Novotny et al.

The most effective dosage of tenecteplase for acute ischemic stroke remains uncertain. The researchers pooled analysis of the NOR‐TEST trials (Norwegian Tenecteplase Stroke Trials), which aimed to evaluate the efficacy and safety of tenecteplase at 0.4 mg/kg.

This retrospective study encompassed a review of the NOR‐TEST and NOR‐TEST 2A PROBE (Prospective Randomized Open, Blinded End‐point) trials. Patients were randomly assigned to receive either tenecteplase at 0.4 mg/kg or alteplase at 0.9 mg/kg. The primary goal was to assess favorable functional outcomes at 3 months, defined as a modified Rankin Scale score of 0–1 or a return to baseline if the pre-stroke modified Rankin Scale score was 2. Secondary outcomes included favorable functional and clinical outcomes as well as safety data. The pooled analysis incorporated patients with a National Institutes of Health Stroke Scale score ≥6 from both trials. A post hoc analysis included patients with a National Institutes of Health Stroke Scale score ≤5 from NOR‐TEST. In the per‐protocol analysis of 483 patients (235 receiving tenecteplase and 248 receiving alteplase), better functional outcomes were observed in the alteplase group at the cutoff modified Rankin Scale score of 2 (odds ratio [OR], 0.52 [95% CI, 0.33–0.80]; P=0.003) and indicated by ordinal shift analysis (OR, 1.64 [95% CI, 1.17–2.28]; P=0.004). However, 3‐month mortality was higher in the tenecteplase group (OR, 2.48 [95% CI, 1.20–5.10]; P=0.01). Notably, mortality and intracranial hemorrhage rates were elevated in severe stroke patients receiving tenecteplase, whereas these rates remained similar between alteplase and tenecteplase in moderate and mild strokes.

In conclusion, the 0.4 mg/kg dosage of tenecteplase presents safety concerns in moderate and severe strokes, with an apparent increased risk of death and intracranial hemorrhage, particularly in more severe strokes. Future trials should explore lower doses of tenecteplase to establish safer and more effective treatment approaches.

Source: ahajournals.org/doi/10.1161/JAHA.123.030320