SOURCES: Bala F, Singh N, Buck B, et al. Safety and efficacy of tenecteplase compared with alteplase in patients with large vessel occlusion stroke: A prespecified secondary analysis of the ACT randomized clinical trial. JAMA Neurology 2023;80:824-832.
Warach SJ, Ranta A, Kim J, et al. 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. JAMA Neurology 2023;80:732-738.
Since 1996, when the U.S. Food and Drug Administration approved the use of intravenous alteplase for the treatment of acute ischemic stroke, there has been a steady increase in the adoption of both intravenous thrombolysis as well as endovascular thrombolysis and mechanical thrombectomy for the treatment of patients with acute ischemic stroke and large vessel occlusion. There now is extensive experience with the use of tenecteplase for the treatment of acute ischemic stroke. It has been shown to be equally efficacious, with a similar risk profile as alteplase.
Tenecteplase is a genetically modified version of alteplase that has much higher specificity for fibrin, has an increased resistance to plasminogen activator inhibitor, has a longer half-life that allows for rapid bolus administration, and has been used extensively as the standard treatment for ST-elevation acute myocardial infarction. In Western Europe and much of Asia, it has been adopted as the standard of care for the treatment of acute ischemic stroke. Because of its rapid bolus administration, it has shortened the time of arrival for patients to thrombectomy-ready centers and has sped up treatment for patients who were treated in mobile stroke unit ambulances.
However, the use of thrombolytics prior to the initiation of endovascular thrombectomy has remained controversial, and the value of tenecteplase vs. alteplase in these clinical situations has been debated.
Bala et al performed a prespecified analysis of the data that came out of the ACT randomized clinical trial that enrolled 1,600 patients at 22 different primary and comprehensive stroke centers across Canada from 2019 until 2022. Patients who presented within 4.5 hours of symptom onset were randomly assigned to receive either intravenous tenecteplase or alteplase and were analyzed for baseline large vessel occlusion (LVO) of either the internal carotid artery, M1-middle cerebral artery (MCA), M2-MCA, or basilar occlusions. Randomized patients were treated with intravenous tenecteplase 0.25 mg/kg or intravenous alteplase 0.9 mg/kg. The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90 days. Secondary outcomes were an mRS of 0-2, mortality, and symptomatic intracerebral hemorrhage. Angiographic outcomes were assessed for successful reperfusion on the first angiogram and the final angiogram. Multivariate analyses were performed to adjust outcomes for age, sex, National Institutes of Health Stroke Scale (NIHSS) score, symptom onset to needle time, and location of occlusion.
A total of 1,577 patients completed the study, with 33% having an LVO. The average age was 74 years, 54% were women, and, of the patients with LVO, 26% had an internal carotid artery occlusion, 46% had an M1-MCA occlusion, 23% had an M2-MCA occlusion, and 6% had basilar artery occlusion. The primary outcome, mRS score of 0-1, was achieved in 33% in the tenecteplase group vs. 30% in the alteplase group.
There was no significant difference in achieving mRS 0-2 (49% vs. 51%), symptomatic intracerebral hemorrhage (6.1% vs. 4.3%), and mortality (20% vs. 18%). No difference was noted in successful reperfusion rates at the time of the first angiogram (9.2% vs. 10.5%) and the final angiogram after thrombectomy (84.5% vs. 88.9%). Bala et al concluded that, for patients referred for endovascular thrombectomy, treating them initially with intravenous tenecteplase or alteplase resulted in the same degree of reperfusion, safety profile, and clinical functional outcomes at 90 days.
In a related study, Warach et al looked at the rates of symptomatic intracranial hemorrhage in a large trial (CERTAIN) that compared tenecteplase and alteplase in the treatment of acute ischemic stroke in more than 100 hospitals throughout New Zealand, Australia, and the United States from 2018 until 2021. This was a retrospective observational study using data collected in the assessment of patient outcomes. The primary outcome of this study was the frequency of symptomatic intracerebral hemorrhage, defined as clinical worsening by at least four points on the NIHSS attributed to a parenchymal, subarachnoid, or intraventricular hemorrhage. Differences between the frequency of hemorrhage in patients treated with tenecteplase and alteplase were assessed and adjusted for age, sex, NIHSS score, and thrombectomy. A total of 9,238 patients who received thrombolysis all were included in this retrospective study.
The median age was 71 years and 48% of the patients were female. Tenecteplase was given to 1,925 patients. The tenecteplase group had an older median age of 73 years vs. 70 years, and were more likely to be male (54% vs. 51%). Tenecteplase patients had a higher NIHSS score and more frequently underwent endovascular thrombectomy. The proportion of patients who had symptomatic intracerebral hemorrhage was 1.8% for tenecteplase and 3.6% for alteplase (P < 0.001). The adjusted odds ratio for hemorrhage with tenecteplase was 0.42 (P < 0.01). The results were the same in both the thrombectomy and the non-thrombectomy subgroups.
The investigators concluded that treating patients who are undergoing thrombectomy with 0.25 mg/kg of tenecteplase was associated with a lower risk of developing symptomatic intracerebral hemorrhage than if they were treated with alteplase. This also applied to those patients who did not undergo thrombectomy and supports the real-world practice of using tenecteplase as a first-line thrombolytic medication for patients with acute ischemic stroke.
