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Observational Study
. 2023 Jul 1;80(7):732-738.
doi: 10.1001/jamaneurol.2023.1449.

Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration

Steven J Warach  1   2 , Anna Ranta  3   4 , Joosup Kim  5 , Shlee S Song  6   7   8 , Adam Wallace  9 , James Beharry  10   11 , Daniel Gibson  9 , Dominique A Cadilhac  5 , Christopher F Bladin  12   13 , Timothy J Kleinig  14 , Jackson Harvey  14 , Logesh Palanikumar  14 , Vinodh T Doss  15 , Ruth Marescalco  15 , John N Fink  11 , Alicia Tyson  4 , Konrad H Schlick  6 , Lydia Noh  6 , Duncan Wilson  11 , Sonia Figueroa  6 , Marco A Pech Jr  7 , Laurie B Paletz  6 , Maya K Lewis  8 , Marissa Castro  6   8 , Daniel H Sahlein  16   17 , E Frank Lafranchise  18 , Justin Sandall  19 , Kaiz S Asif  20 , Scott R Geraghty  20 , Paul A Cullis  21 , Tim Malisch  20 , Terry A Neill Jr  22 , Marian P LaMonte  23 , Bruce C V Campbell  10 , Teddy Y Wu  11
Affiliations
Observational Study

Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration

Steven J Warach et al. JAMA Neurol. .

Abstract

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 < .001), more likely to be male (1034 of 7313 [54%] vs 3755 of 1925 [51%]; P < .01), had higher NIHSS scores (median [IQR], 9 [5-17] vs 7 [4-14]; P < .001), and more frequently underwent endovascular thrombectomy (38% vs 20%; P < .001). The proportion of patients with sICH was 1.8% for tenecteplase and 3.6% for alteplase (P < .001), with an adjusted odds ratio (aOR) of 0.42 (95% CI, 0.30-0.58; P < .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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Warach reported consulting fees from Genentech and BrainsGate outside the submitted work. Dr Ranta reported grants from Te Whatu Ora - Health NZ supporting the national stroke register, one of the data sources for this study, and from Health Research Council funding unrelated research outside the submitted work. Dr Song reported grants from Genentech for serving as site principal investigator for the TIMELESS clinical trial during the conduct of the study and grants from Genentech and speaker fees from the Clinical Neurological Society of America outside the submitted work. Dr Wallace reported personal fees from Robins Kaplan and Feldman Shephard outside the submitted work. Dr Gibson reported personal fees from Siemens Healthineers and iSchemaView outside the submitted work. Dr Cadilhac reported grants from Boehringer Ingelheim paid to institution, Bristol Myers Squibb paid to institution, and Amgen paid to institution outside the submitted work. Dr Kleinig reported accommodation and travel provided from Boehringer Ingelheim outside the submitted work. Dr Sahlein reported speaker fees from Medtronic, grants from Microvention, and other from Siemens, Tellybelly, and Scientia outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Rates of Intracranial Hemorrhage
See this image and copyright information in PMC

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