Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke
Authors: Warach Steven J. , Ranta Anna , Kim Joosup , Song Shlee S. , Wallace Adam , Beharry James , Gibson Daniel , Cadilhac Dominique A. , Bladin Christopher F. , Kleinig Timothy J. , Harvey Jackson , Palanikumar Logesh , Doss Vinodh T. , Marescalco Ruth , Fink John N. , Tyson Alicia , Schlick Konrad H. , Noh Lydia , Wilson Duncan , Figueroa Sonia , Pech Marco A. , Paletz Laurie B. , Lewis Maya K. , Castro Marissa , Sahlein Daniel H. , Lafranchise E. Frank , Sandall Justin , Asif Kaiz S. , Geraghty Scott R. , Cullis Paul A. , Malisch Tim , Neill Terry A. , LaMonte Marian P. , Campbell Bruce C. V. , Wu Teddy Y. 
Published: May 2023

Importance

Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy. Many stroke centers have adopted 0.25-mg/kg tenecteplase instead of alteplase for stroke thrombolysis based on evidence from randomized comparisons to alteplase as well as for its practical advantages. There have been no significant differences in symptomatic intracranial hemorrhage (sICH) reported from randomized clinical trials or published case series for the 0.25-mg/Kg dose.

Objective

To assess the risk of sICH following ischemic stroke in patients treated with tenecteplase compared to those treated with alteplase.

Design, Setting, and Participants

This was a retrospective observational study using data from the large multicenter international Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) collaboration comprising deidentified data on patients with ischemic stroke treated with intravenous thrombolysis. Data from more than 100 hospitals in New Zealand, Australia, and the US that used alteplase or tenecteplase for patients treated between July 1, 2018, and June 30, 2021, were included for analysis. Participating centers included a mix of nonthrombectomy- and thrombectomy-capacity comprehensive stroke centers. Standardized data were abstracted and harmonized from local or regional clinical registries. Consecutive patients with acute ischemic stroke who were considered eligible and received thrombolysis at the participating stroke registries during the study period were included. All 9238 patients who received thrombolysis were included in this retrospective analysis.

Main Outcomes and Measures

sICH was defined as clinical worsening of at least 4 points on the National Institutes of Health Stroke Scale (NIHSS), attributed to parenchymal hematoma, subarachnoid, or intraventricular hemorrhage. Differences between tenecteplase and alteplase in the risk of sICH were assessed using logistic regression, adjusted for age, sex, NIHSS score, and thrombectomy.

Results

Of the 9238 patients included in the analysis, the median (IQR) age was 71 (59-80) years, and 4449 patients (48%) were female. Tenecteplase was administered to 1925 patients. The tenecteplase group was older (median [IQR], 73 [61-81] years vs 70 [58-80] years; P &amp;lt; .001), more likely to be male (1034 of 7313 [54%] vs 3755 of 1925 [51%]; P &amp;lt; .01), had higher NIHSS scores (median [IQR], 9 [5-17] vs 7 [4-14]; P &amp;lt; .001), and more frequently underwent endovascular thrombectomy (38% vs 20%; P &amp;lt; .001). The proportion of patients with sICH was 1.8% for tenecteplase and 3.6% for alteplase (P &amp;lt; .001), with an adjusted odds ratio (aOR) of 0.42 (95% CI, 0.30-0.58; P &amp;lt; .01). Similar results were observed in both thrombectomy and nonthrombectomy subgroups.

Conclusions and Relevance

In this large study, ischemic stroke treatment with 0.25-mg/kg tenecteplase was associated with lower odds of sICH than treatment with alteplase. The results provide evidence supporting the safety of tenecteplase for stroke thrombolysis in real-world clinical practice.