Tenecteplase Versus Alteplase for Acute Stroke: Mortality and Bleeding Complications

Study objective: Intravenous thrombolysis with alteplase has been the foundation of initial treatment of acute ischemic stroke for several decades. Tenecteplase is a thrombolytic agent that offers logistical advantages in cost and administration relative to alteplase. There is evidence that tenecteplase has at least similar efficacy and safety outcomes compared with alteplase for stroke. In this study, we compared tenecteplase versus alteplase for acute stroke in a large retrospective US database (TriNetX) regarding the following 3 outcomes: (1) mortality, (2) intracranial hemorrhage, and (3) the need for acute blood transfusions. Methods: In this retrospective study using the US cohort of 54 academic medical centers/health care organizations in the TriNetX database, we identified 3,432 patients treated with tenecteplase and 55,894 patients treated with alteplase for stroke after January 1, 2012. Propensity score matching was performed on basic demographic information and 7 previous clinical diagnostic groups, resulting in a total of 6,864 patients with acute stroke evenly matched between groups. Mortality rates, the frequency of intracranial hemorrhage, and blood transfusions (as a marker of significant blood loss) were recorded for each group over the ensuing 7- and 30-day periods. Secondary subgroup analyses were conducted on a cohort treated from 2021 to 2022 in an attempt to determine whether temporal differences in acute ischemic stroke treatment would alter the results. Results: Patients treated with tenecteplase had a significantly lower mortality rate (8.2% versus 9.8%; risk ratio [RR], 0.832) and lower risk of major bleeding as measured by the frequency of blood transfusions (0.3% versus 1.4%; RR, 0.207) than alteplase at 30 days after thrombolysis for stroke. In the larger 10-year data set of patients with stroke treated after January 1, 2012, patients receiving tenecteplase were not found to have a statistically different incidence of intracranial hemorrhage (3.5% versus 3.0%; RR, 1.185) at 30 days after the administration of the thrombolytic agents in patients. However, a subgroup analysis of 2,216 evenly matched patients with stroke treated from 2021 to 2022 demonstrated notably better survival and statistically lower rates of intracranial hemorrhage than the alteplase group. Conclusion: In our large retrospective multicenter study using real-world evidence from large health care organizations, tenecteplase for the treatment of acute stroke demonstrated a lower mortality rate, decreased intracranial hemorrhage, and less significant blood loss. The favorable mortality and safety profiles observed in this large study, taken together with previous randomized controlled trial data and operational advantages in rapid dosing and cost-effectiveness, all support the preferential use of tenecteplase in patients with ischemic stroke.