Tenecteplase In Ischemic Stroke Research Articles

Treatment times, functional outcome, and hemorrhage rates after switching to tenecteplase for stroke thrombolysis: Insights from the TETRIS registry.

The encouraging efficacy and safety data on intravenous thrombolysis with tenecteplase in ischemic stroke and its practical advantages motivated our centers to switch from alteplase to tenecteplase. We report its impact on treatment times and clinical outcomes. We retrospectively analyzed clinical and procedural data of patients treated with alteplase or tenecteplase in a comprehensive (CSC) and a primary stroke center (PSC), which transitioned respectively in 2019 and 2018. Tenecteplase enabled in-imaging thrombolysis in the CSC. The main outcomes were the imaging-to-thrombolysis and thrombolysis-to-puncture times. We assessed the association of tenecteplase with 3-month functional independence and parenchymal hemorrhage (PH) with multivariable logistic models. We included 795 patients, 387 (48.7%) received alteplase and 408 (51.3%) tenecteplase. Both groups (tenecteplase vs alteplase) were similar in terms of age (75 vs 76 years), baseline NIHSS score (7 vs 7.5) and proportion of patients treated with mechanical thrombectomy (24.1% vs 27.5%). Tenecteplase patients had shorter imaging-to-thrombolysis times (27 vs 36 min, p < 0.0001) mainly driven by patients treated in the CSC (22 vs 38 min, p < 0.001). In the PSC, tenecteplase patients had shorter thrombolysis-to-puncture times (84 vs 95 min, p = 0.02), reflecting faster interhospital transfer for MT. 3-month functional independence rate was higher in the tenecteplase group (62.8% vs 53.4%, p < 0.01). In the multivariable analysis, tenecteplase was significantly associated with functional independence (ORa 1.68, 95% CI 1.15-2.48, p < 0.01), but not with PH (ORa 0.68, 95% CI 0.41-1.12, p = 0.13). Switch from alteplase to tenecteplase reduced process times and may improve functional outcome, with similar safety profile.

Tenecteplase in Ischemic Stroke: Challenge and Opportunity.

Purpose of ReviewIntravenous thrombolysis is the first-line therapy for ischemic stroke, and alteplase has been used as an intravenous thrombolysis drug for over 20 years. However, considering its low rate of recanalization and risk of intracerebral hemorrhage, alteplase may not be the optimal thrombolytic drug of choice for ischemic stroke. Tenecteplase (TNK) is a genetically engineered, mutant, tissue plasminogen activator that is a potential substitute to alteplase in ischemic stroke. The pharmacokinetic advantages of TNK include greater fibrin selectivity than alteplase and prolonged half-life time. In this review, we have summarized the clinical trials of TNK in ischemic stroke.Recent FindingsClinical trials showed a higher recanalization rate of TNK over alteplase without increasing the rate of intracerebral hemorrhage. However, not all clinical trials showed superiority of TNK over alteplase in functional outcomes and early neurological improvement. TNK was superior to alteplase in terms of recanalization in patients who fulfilled the imaging mismatch criteria and in those planning to undergo mechanical thrombectomy.SummaryTNK has the potential to substitute alteplase for ischemic stroke therapy. Future TNK clinical trials that target functional outcomes are warranted.

Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials.

We pooled 2 clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of tenecteplase and the other that showed no difference between the treatments in patient clinical outcomes. We tested the hypotheses that reperfusion therapy with tenecteplase would be superior to alteplase in improving functional outcomes in the group of patients with target mismatch as identified with advanced imaging. We investigated whether tenecteplase-treated patients had a different 24-hour reduction in the National Institutes of Health Stroke Scale and a favorable odds ratio of a modified Rankin scale score of 0 to 1 versus 2 to 6 compared with alteplase-treated patients using linear regression to generate odds ratios. Imaging outcomes included rates of vessel recanalization and infarct growth at 24 hours and occurrence of large parenchymal hematoma. Baseline computed tomography perfusion was analyzed to assess whether patients met the target mismatch criteria (absolute mismatch volume >15 mL, mismatch ratio >1.8, baseline ischemic core <70 mL, and volume of severely hypoperfused tissue <100 mL). Patients meeting target mismatch criteria were analyzed as a subgroup to identify whether they had different treatment responses from the pooled group. Of 146 pooled patients, 71 received alteplase and 75 received tenecteplase. Tenecteplase-treated patients had greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 7; alteplase, 2; P=0.018) and less parenchymal hematoma (2 of 75 versus 10 of 71; P=0.02). The pooled group did not show improved patient outcomes when treated with tenecteplase (modified Rankin scale score 0-1: odds ratio, 1.77; 95% confidence interval, 0.89-3.51; P=0.102) compared with alteplase therapy. However, in patients with target mismatch (33 tenecteplase, 35 alteplase), treatment with tenecteplase was associated with greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 6; alteplase, 1; P<0.001) and better late independent recovery (modified Rankin scale score 0-1: odds ratio, 2.33; 95% confidence interval, 1.13-5.94; P=0.032) than those treated with alteplase. Tenecteplase may offer an improved efficacy and safety profile compared with alteplase, benefits possibly exaggerated in patients with baseline computed tomography perfusion-defined target mismatch. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472926. URL: https://www.anzctr.org.au. Unique identifier: ACTRN12608000466347.

Intravenous tenecteplase in acute ischemic stroke: an updated review

Tenecteplase in a genetically engineered variant of alteplase. Although the two have the same mechanism of action, tenecteplase has properties that makes it a seemingly more advantageous thrombolytic. Because of its rapid single-bolus administration, its use is favored over alteplase in the treatment of acute myocardial infarction. Over the past few years, several clinical studies have been conducted to assess the safety, feasibility, and efficacy of tenecteplase in ischemic stroke. In spite of the mixed results of these studies, experimentation with tenecteplase continues in from of clinical trials. In this article, the utility of tenecteplase in ischemic stroke will be discussed.