Literature
Clinical Pearls & Morning Reports
Published February 21, 2024
Did tenecteplase administered 4.5 to 24 hours after stroke onset improve clinical outcomes as compared with placebo in this trial?
Albers et al. conducted a double-blind, randomized, placebo-controlled trial that assessed the effectiveness of tenecteplase administered 4.5 to 24 hours after stroke onset in patients with occlusions of the internal carotid artery or middle cerebral artery and imaging evidence of salvageable ischemic brain tissue. Read the NEJM Original Article here.
Clinical Pearls
Q: What is tenecteplase?
A: Intravenous thrombolytic therapy with alteplase has generally been the standard care for eligible patients within 4.5 hours after the onset of ischemic stroke. Tenecteplase is a modified form of human tissue plasminogen activator that was approved in 2000 to reduce mortality among patients with acute myocardial infarction. Several trials have shown the noninferiority of tenecteplase to alteplase when treatment is begun within 4.5 hours after stroke onset, and the most recent American Heart Association–American Stroke Association guidelines for acute ischemic stroke indicate that tenecteplase is a reasonable alternative to alteplase in specific patient populations.
Q: What is known about the feasibility of treatment with tenecteplase more than 4.5 hours after stroke onset?
A: Data regarding the use of tenecteplase beyond 4.5 hours after symptom onset are limited. A trial of tenecteplase in patients who had stroke symptoms when they awoke, but who were not selected on the basis of CT perfusion imaging or perfusion–diffusion MRI, showed that tenecteplase therapy was not associated with better functional outcomes than placebo; however, safety results were similar to those of thrombolytic therapy given within 4.5 hours after onset. A proof-of-concept trial showed the feasibility of treatment with tenecteplase administered no more than 24 hours after stroke onset in patients with evidence of salvageable tissue on CT perfusion imaging.
Morning Report Questions
Q: Did tenecteplase administered 4.5 to 24 hours after stroke onset improve clinical outcomes as compared with placebo in this trial?
A: The primary outcome was the ordinal score on the modified Rankin scale at day 90. The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death). In this trial, the authors found no benefit in functional outcome with tenecteplase as compared with placebo administered 4.5 to 24 hours after symptom onset in patients with ischemic stroke who had been selected on the basis of a favorable perfusion-imaging profile, most of whom subsequently underwent endovascular therapy. The median modified Rankin scale score was 3 in each group. The adjusted common odds ratio of the modified Rankin scale at 90 days was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45).
Q: Was tenecteplase associated with an increase in symptomatic intracerebral hemorrhage in the trial?
A: Mortality at 90 days did not differ appreciably between the two trial groups (19.7% in the tenecteplase group and 18.2% in the placebo group). The incidence of symptomatic intracerebral hemorrhage was similar in the two groups (in 7 patients [3.2%] in the tenecteplase group and in 5 [2.3%] in the placebo group), as was the incidence of parenchymal hematoma type 2 or any intracranial hemorrhage. The incidence of adverse events, serious adverse events, and withdrawal from the trial due to adverse events did not differ appreciably between the groups.