Thrombolysis in acute retinal ischemia treated with tenecteplase.

Central retinal artery occlusion (CRAO), a type of acute retinal arterial ischemia, analogous to an ocular stroke, is a medical emergency that warrants immediate diagnosis and treatment. CRAO usually presents with sudden, painless, monocular vision loss. Ipsilateral carotid artery disease is an important associated finding in these patients. The primary limitation to effective treatment of CRAO is that patients are rarely seen in the acute stage. Moreover, there are no guidelines for effective treatment. We report a patient with right CRAO whose treatment with intravenous thrombolysis with tenecteplase and anterior chamber paracentesis with ocular massage resulted in a good clinical outcome.

Functional Outcome and Hemorrhage Rates After Bridging Therapy With Tenecteplase or Alteplase in Patients With Large Ischemic Core.

BACKGROUND AND OBJECTIVES: IV tenecteplase is an alternative to alteplase before mechanical thrombectomy (MT) in patients with large-vessel occlusion (LVO) ischemic stroke. Little data are available on its use in patients with large ischemic core. We aimed to compare the efficacy and safety of both thrombolytics in this population. METHODS: We conducted a retrospective analysis of patients with anterior circulation LVO strokes and diffusion-weighed imaging Alberta Stroke Program Early CT Score (DWI-ASPECTS) ≤5 treated with tenecteplase or alteplase before MT from the TETRIS (tenecteplase) and ETIS (alteplase) French multicenter registries. Primary outcome was reduced disability at 3 months (ordinal analysis of the modified Rankin scale [mRS]). Safety outcomes were 3-month mortality, parenchymal hematoma (PH), and symptomatic intracranial hemorrhage (sICH). We used propensity score overlap weighting to reduce baseline differences between treatment groups. RESULTS: We analyzed 647 patients (tenecteplase: n = 194; alteplase: n = 453; inclusion period 2015-2022). Median (interquartile range) age was 71 (57-81) years, with NIH Stroke Scale score 19 (16-22), DWI-ASPECTS 4 (3-5), and last seen well-to-IV thrombolysis and puncture times 165 minutes (130-226) and 260 minutes (203-349), respectively. After MT, the successful reperfusion rate was 83.1%. After propensity score overlap weighting, all baseline variables were well balanced between both treatment groups. Compared with patients treated with alteplase, patients treated with tenecteplase had better 3-month mRS (common odds ratio [OR] for reduced disability: 1.37, 1.01-1.87, p = 0.046) and lower 3-month mortality (OR 0.52, 0.33-0.81, p < 0.01). There were no significant differences between thrombolytics for PH (OR 0.84, 0.55-1.30, p = 0.44) and sICH incidence (OR 0.70, 0.42-1.18, p = 0.18). DISCUSSION: Our data are encouraging regarding the efficacy and reassuring regarding the safety of tenecteplase compared with that of alteplase in bridging therapy for patients with LVO strokes and a large ischemic core in routine clinical care. These results support its consideration as an alternative to alteplase in bridging therapy for patients with large ischemic cores. TRIALS REGISTRATION INFORMATION: NCT03776877 (ETIS registry) and NCT05534360 (TETRIS registry). CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with anterior circulation LVO stroke and DWI-ASPECTS ≤5 treated with tenecteplase vs alteplase before MT experienced better functional outcomes and lower mortality at 3 months.

[Therapeutic effect of intravenous thrombolysis with tenecteplase on patients with post awakening branch atheromatous disease].

Objective: To investigate the efficacy and safety of intravenous thrombolysis with Tenecteplase (TNK) in patients with post-awakening branch atheromatous disease (BAD). Methods: A retrospective collection was conducted on 178 patients with post-awakening BAD admitted to the Stroke Centre of Zhengzhou People's Hospital from January 2017 to June 2023, who had a mismatch in DWI/FLAIR on magnetic resonance imaging. The patients were divided into thrombolysis group (60 patients) and control group (118 patients) according to whether or not they were applied to intravenous thrombolysis by TNK. Propensity score matching (PSM) was used to pair and balance the confounding factors at 1∶1 between the two groups, and the 90-d long-term prognosis of the patients was assessed using the modified Rankin Scale (mRS) and the Barthel Index (BI). The National Institutes of Health Stroke Scale (NIHSS) score was used to compare the early neurological changes between the two groups.The differences in clinical outcomes were compared between the two groups. Results: Fifty-two pairs of patients, 65 males and 39 females, aged (60±9) years, were successfully matched by PSM. The thrombolysis group had lower NIHSS score than that of the control group at 24 h, 7 d, 14 d after treatment or at discharge [3(2, 5) vs 4(3, 7), 3(2, 5) vs 4(3, 5), and 2(1, 4) vs 3(2, 4)], and shorter hospital stay than that of the control group [9(7, 12) d vs 11(9, 13) d], and at the same time, the thrombolysis group was less likely to experience early neurological deterioration (END) [9.6% (5/52) vs 28.9% (15/52)], and the proportion of 90 d mRS≤1, mRS≤2, and BI scores were higher than those in the control group [63.5% (33/52) vs 30.8% (16/52), 82.7% (43/52) vs 59.6% (31/52), and (91±8) points vs (82±8) points ], all differences were statistically significant (P<0.05). The percentage of mRS≥4 points was higher in the control group than that in the thrombolysis group [23.1% (12/52) vs 7.7% (4/52)]. One case of intracranial haemorrhage occurred in the thrombolysis group, and 1 case in the control group died of pulmonary infection within 90 d of follow-up, with a case-fatality rate of 1.9% (1/52). Conclusion: In the patients with post-awakening BAD screened by MRI, TNK intravenous thrombolysis can significantly reduce the risk of END, improving long-term prognosis and has a high safety.

Lack of Interactions Between Alteplase/Tenecteplase and the Adenosine A1R/A3R Agonist AST-004.

BACKGROUND: AST-004, a small molecule agonist of the adenosine A1 and A3 receptors, is a potential cerebroprotectant for patients with acute stroke and is currently in clinical trials. Drug-drug interactions are critically important to assess in the context of acute stroke care. Lytic therapy with tPA (tissue-type plasminogen activator)-induced plasmin formation (alteplase) is the only available pharmacotherapy for acute stroke. Consequently, it is imperative to evaluate potential interactions between AST-004 and tPAs such as alteplase and tenecteplase. METHODS: The interactions between AST-004 and tPAs were evaluated in 3 ways in preparation for AST-004 phase II trials. First, the metabolic stability of AST-004 was determined in the presence of alteplase and plasmin. Second, the potential for AST-004 to influence the thrombolytic efficacy of alteplase and tenecteplase was evaluated with an in vitro assay system utilizing a fluorogenic substrate of plasmin. Finally, the potential for AST-004 to influence the thrombolytic efficacy of alteplase was also determined with an in vitro thrombolysis assay of human blood thrombi. RESULTS: Neither alteplase nor plasmin affected the stability of AST-004 in vitro. In 2 different in vitro systems, AST-004 had no effect on the ability of alteplase or tenecteplase to generate plasmin, and AST-004 had no effect on the thrombolytic efficacy of alteplase to lyse blood clots in human blood. CONCLUSIONS: These studies indicate that there will be no interactions between AST-004 and tPAs such as alteplase or tenecteplase in patients with stroke undergoing thrombolytic therapy.

Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial.

BACKGROUND: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. METHODS: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. FINDINGS: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059). INTERPRETATION: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. FUNDING: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.

Comprehensive Review of Tenecteplase for Thrombolysis in Acute Ischemic Stroke.

Although intravenous thrombolysis with alteplase remains the primary treatment for acute ischemic stroke, tenecteplase has shown potential advantages over alteplase. Animal studies have demonstrated the favorable pharmacokinetics and pharmacodynamics of tenecteplase. Moreover, it is easier to administer. Clinical trials have demonstrated that tenecteplase is not inferior to alteplase and may even be superior in cases of acute ischemic stroke with large vessel occlusion. Current evidence supports the time and cost benefits of tenecteplase, suggesting that it could potentially replace alteplase as the main option for thrombolytic therapy, especially in patients with large vessel occlusion.

Tenecteplase versus Alteplase before thrombectomy: A comprehensive evaluation of clinical and angiographic impact: Insights from the ETIS registry.

INTRODUCTION: Data on prior use of Tenecteplase versus Alteplase in acute stroke management by mechanical thrombectomy are controversial. Our primary objective was to make a comprehensive comparative assessment of clinical and angiographic efficacy and safety outcomes in a large prospective observational study. METHODS: We included stroke patients who were eligible for intravenous thrombolysis and endovascular thrombectomy between 2019 and 2021, from an ongoing registry in twenty comprehensive stroke centers in France. We divided patients into two groups based on the thrombolytic agent used (Alteplase vs Tenecteplase). We then compared their treatment times, and their angiographic (TICI scale), clinical (mRS at three months and sICH) and safety outcomes after controlling for potential confounders using propensity score methods. RESULTS: We evaluated 1131 patients having undergone thrombectomy for the final analysis, 250 received Tenecteplase and 881 Alteplase. Both groups were of the same median age (75 vs 74 respectively), and had the same baseline NIHSS score (16) and ASPECTS (8). There was no significant difference for First Pass Effect (OR 0.93, 95 % CI 0.76-1.14, p = 0.75), time required for reperfusion (OR 0.03, 95 % CI 0.09-0.16, p = 0.49), or for final reperfusion status. Clinically, functional independence at 90 days was similar in both groups (OR 0.82, 95 % CI 0.61-1.10, p = 0.18) with the same risk of sICH (OR 1.36, 95 % CI 0.77-2.41, p = 0.28). However, Tenecteplase patients had shorter imaging-to-groin puncture times (99 vs 142 min, p < 0.05). CONCLUSIONS: Tenecteplase showed no better clinical or angiographic impact on thrombectomy compared to Alteplase. Nevertheless, it appeared associated with a shorter thrombolysis-to-groin puncture time.

Association of Time to Thrombolysis With Early Reperfusion After Alteplase and Tenecteplase in Patients With Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: Early treatment with intravenous alteplase increases the probability of lytic-induced reperfusion in large vessel occlusion (LVO) patients. The relationship of tenecteplase-induced reperfusion and the timing of thrombolytic administration has not been explored. In this study, we performed a comparative analysis of tenecteplase and alteplase reperfusion rates and assessed their relationship to the time of thrombolytic administration. METHODS: Patients who were initially treated with a thrombolytic within 4.5 hours of symptom onset were pooled from the Royal Melbourne Stroke Registry, EXTEND-IA, EXTEND-IA TNK, and EXTEND-IA TNK part 2 trials. The primary outcome, thrombolytic-induced reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion at initial angiographic assessment (or repeat CT perfusion/angiography). We compared the treatment effect of tenecteplase and alteplase through fixed-effects Poisson regression modelling. RESULTS: Among 846 patients included in the primary analysis, early reperfusion was observed in 173 (20%) patients (tenecteplase: 98/470 [21%], onset-to-thrombolytic time: 132 minutes [interquartile range (IQR): 99-170], and thrombolytic-to-assessment time: 61 minutes [IQR: 39-96]; alteplase: 75/376 [19%], onset-to-thrombolytic time: 143 minutes [IQR: 105-180], thrombolytic-to-assessment time: 92 minutes [IQR: 63-144]). Earlier onset-to-thrombolytic administration times were associated with an increased probability of thrombolytic-induced reperfusion in patients treated with either tenecteplase (adjusted risk ratio [aRR] 1.05 per 15 minutes [95% confidence interval (CI) 1.00-1.12] or alteplase (aRR 1.06 per 15 minutes [95% CI 1.00-1.13]). Tenecteplase remained associated with higher rates of reperfusion vs alteplase after adjustment for onset-to-thrombolytic time, occlusion site, thrombolytic-to-assessment time, and study as a fixed effect, (adjusted incidence rate ratio: 1.41 [95% CI 1.02-1.93]). No significant treatment-by-time interaction was observed (p = 0.87). DISCUSSION: In patients with LVO presenting within 4.5 hours of symptom onset, earlier thrombolytic administration increased successful reperfusion rates. Compared with alteplase, tenecteplase was associated with a higher probability of lytic-induced reperfusion, independent of onset-to-lytic administration times. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifiers: NCT02388061, NCT03340493. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with LVO receiving a thrombolytic, reperfusion was more likely with tenecteplase than alteplase.

Efficacy and safety outcomes of Tenecteplase versus Alteplase for thrombolysis of acute ischemic stroke: A meta-analysis of 9 randomized controlled trials.

BACKGROUND: In recent years, Tenecteplase (TNK), a genetically modified variant of alteplase, has been verified as a potential substitute for alteplase in the reperfusion therapy of acute ischemic stroke (AIS). Given the emergence of new randomized controlled trials (RCTs) of this subject, a meta-analysis was conducted to evaluate the present comparative evidence regarding the efficacy and safety outcomes of TNK and alteplase in thrombolysis for AIS. METHODS: Following predefined inclusion criteria, we searched the databases of PubMed, Web of Science, and Cochrane Library. RCTs satisfying our inclusion criteria were selected for meta-analysis. Outcome indicators were categorized into efficacy outcomes (early vessel recanalization, excellent recovery, good recovery and early neurological improvement) and safety outcomes (poor recovery, symptomatic intracerebral hemorrhage, parenchymal hemorrhage type 2(PH2) post thrombolysis, and mortality). We extracted data on efficacy outcomes and safety outcomes for patients with AIS in the TNK group at a dose of 0.25 mg/kg and the alteplase group at a dose of 0.9 mg/kg, and expressed the relative risks between the 2 groups as odds ratios (ORs) and 95% confidence intervals (CIs) using the Mantel-Haenszel method. For further insight, we performed a network meta-analysis using a Bayesian framework to compare different doses of TNK (0.1, 0.25, 0.32, and 0.4 mg/kg) with alteplase (0.9 mg/kg). RESULTS: A total of 2994 patients in 9 RCTs comparing efficacy and safety outcomes in patients with AIS treated with TNK and alteplase were included. In a pairwise analysis of TNK 0.25 mg/kg and alteplase 0.9 mg/kg, regarding efficacy outcomes, the aggregated results show that TNK 0.25 mg/kg statistically significant increased early vessel recanalization (N = 368, TNK vs. alteplase, OR: 2.07,95%CI: [1.19,3.59], I2 = 0%) and excellent recovery (N = 3548, TNK vs. alteplase, OR: 1.15,95%CI: [1.01,1.32], I2 = 0%). There was no significant difference in good recovery (N = 3486, TNK vs. alteplase, OR: 1.38,95%CI: [0.89,2.15], I2 = 84%) or early neurological improvement (N = 1686, TNK vs. alteplase, OR: 1.06,95%CI: [0.87,1.28], I2 = 24%) between the TNK 0.25 mg/kg group and the alteplase 0.9 mg/kg group. In the safety outcomes, pooled results showed no significant difference in poor recovery (N = 3548, TNK vs. alteplase, OR: 0.94,95%CI: [0.81,1.10], I2 = 0%) and symptomatic intracerebral hemorrhage (N = 3567, TNK vs. alteplase, OR: 1.06,95%CI: [0.70,1.60], I2 = 0%) and PH2(N = 3103, TNK vs. alteplase, OR: 1.26,95%CI:[0.39,4.07], I2 = 56%)and mortality (N = 3447, TNK vs. alteplase, OR: 0.99,95%CI: [0.80,1.23], I2 = 33%) between the TNK group and the alteplase group. In a network meta-analysis, competing treatments were not significantly different from one another (TNK 0.1 mg/kg, TNK 0.25 mg/kg, TNK 0.32 mg/kg, TNK 0.4 mg/kg, alteplase 0.9 mg/kg) in either efficacy outcomes or safety outcomes. CONCLUSION: In this analysis of 9 RCTs in patients with AIS, TNK 0.25 mg/kg was comparable to alteplase 0.9 mg/kg from the perspective of efficacy outcomes and safety outcomes after thrombolysis within 4.5 h of AIS occurrence.

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

A bibliometric analysis of tenecteplase research utilizing a commonly used citation index.

BACKGROUND AND PURPOSE: Tenecteplase is increasingly being used as a first-line treatment for acute ischemic stroke after several randomized studies demonstrated its safety and efficacy, resulting in a massive increase in the number of published studies on this topic. Our aim was to investigate the most impactful authors and relevant journals that have been instrumental in validating this treatment, in hopes of identifying objective research trends that may assist scientists, health organizations, and funding agencies to collaborate and plan future avenues of research. METHODS: Using the search terms "Tenecteplase" and "Tenecteplase" AND "Stroke," 2683 and 1150 references were queried, respectively, using the abstract and citation database, Scopus. Scopus Citation Analysis was used to categorize the countries and authors who produced the most research. Metadata was retrieved and transferred to bibliographic visualization software, VOSviewer, for co-authorship and co-occurrence analyses to identify trends in tenecteplase research. RESULTS: Data visualization software identified three tenecteplase research clusters - myocardial infarction, pulmonary embolism, and acute ischemic stroke. Our bibliographic analysis graphically identified that ischemic stroke currently leads both myocardial infarction and pulmonary embolism in annual publications pertaining to tenecteplase therapy, and further pinpointed perfusion imaging and wake-up strokes as the most relevant areas of study. The United States led all countries in tenecteplase publications, including exclusively stroke studies. The European Heart Journal led all journals in overall publications, while Stroke led all journals in stroke-related studies. CONCLUSIONS: Through the use of bibliographic analysis and data visualization, we identified major articles and journals that reflected and shaped the current landscape of tenecteplase; recognized authors who engaged in tenecteplase research as it progressed from cardiopulmonary disease to stroke; and postulated future avenues of research.

Early tirofiban administration after intravenous thrombolysis in acute ischemic stroke (ADVENT): Study protocol of a multicenter, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Nearly half of patients with acute ischemic stroke who undergo intravenous thrombolysis (IVT) fail to achieve excellent functional outcomes. Early administration of tirofiban after IVT may improve patient outcomes. OBJECTIVE: To evaluate the efficacy and safety of early tirofiban administration after intravenous tenecteplase in patients with acute ischemic stroke. METHODS AND DESIGN: The ADVENT trial is a multicenter, randomized, parallel-controlled, double-blind clinical trial. A total of 1084 patients undergoing IVT without subsequent endovascular treatment will be recruited from multiple hospitals in China. Subjects will be randomized in a 1:1 ratio to receive tirofiban or placebo, which will be infused within 6 h after IVT until 24 h after IVT, at 0.4 µg/kg/min for 30 min and then at 0.1 µg/kg/min. The primary efficacy outcome is the proportion of patients with excellent functional outcomes (modified Rankin Scale (mRS) ⩽ 1) at 90 days. Secondary outcomes include the proportion of patients with favorable functional outcomes (mRS ⩽ 2) at 90 days and neurological functional assessments evaluated during hospitalization. Symptomatic intracranial hemorrhage will be the primary safety outcome. Mortality and other adverse events will be recorded. DISCUSSION: This pivotal trial will provide important data on the early administration of antiplatelet therapy after IVT and may promote progress in treatment standards. TRIAL REGISTRY: ClinicalTrials.gov (NCT06045156).

Comparison of pharmacokinetic properties of alteplase and tenecteplase. The future of thrombolysis in acute ischemic stroke.

INTRODUCTION: The drug most frequently used for thrombolysis in cases of acute ischemic stroke (AIS) is alteplase. However, there is moderate-to-high-quality evidence that tenecteplase has similar or higher efficacy and safety. With improved pharmacokinetic properties over alteplase, tenecteplase could be a significant advantage in treating AIS. AREAS COVERED: After conducting an extensive search on Scopus and PubMed, this manuscript reviews and compares the pharmacokinetic properties of alteplase and tenecteplase. Additionally, it provides information on pharmacodynamics, clinical efficacy, safety, tolerability, and drug-drug interactions. EXPERT OPINION: The pharmacokinetic profile of alteplase and tenecteplase is derived from studies in patients with acute myocardial infarction. Thanks to its pharmacokinetic properties, tenecteplase is the drug closest to being the ideal fibrinolytic for AIS. Its longer half-life enables a single-bolus administration, which is particularly useful in emergencies. Tenecteplase has proven to have a good efficacy and safety profile in randomized clinical trials. Although we are awaiting the results of the ongoing phase 3 randomized clinical trials, we believe that tenecteplase has the potential to revolutionize the treatment of AIS through thrombolysis.

Multicenter exploration of tenecteplase transition factors: A quantitative analysis.

BACKGROUND: Tenecteplase (TNK) is gaining recognition as a novel therapy for acute ischemic stroke (AIS). Despite TNK offering a longer half-life, time and cost saving benefits and comparable treatment and safety profiles to Alteplase (ALT), the adoption of TNK as a treatment for AIS presents challenges for hospital systems. OBJECTIVE: Identify barriers and facilitators of TNK implementation at acute care hospitals in Texas. METHODS: This prospective survey used open-ended questions and Likert statements generated from content experts and informed by qualitative research. Stroke clinicians and nurses working at 40 different hospitals in Texas were surveyed using a virtual platform. RESULTS: The 40 hospitals had a median of 34 (IQR 24.5-49) emergency department beds and 42.5 (IQR 23.5-64.5) inpatient stroke beds with 506.5 (IQR 350-797.5) annual stroke admissions. Fifty percent of the hospitals were Comprehensive Stroke Centers, and 18 (45 %) were solely using ALT for treatment of eligible AIS patients. Primary facilitators to TNK transition were team buy-in and a willingness of stroke physicians, nurses, and pharmacists to adopt TNK. Leading barriers were lack of clinical evidence supporting TNK safety profile inadequate evidence supporting TNK use and a lack of American Heart Association guidelines support for TNK administration in all AIS cases. CONCLUSION: Understanding common barriers and facilitators to TNK adoption can assist acute care hospitals deciding to implement TNK as a treatment for AIS. These findings will be used to design a TNK adoption Toolkit, utilizing implementation science techniques, to address identified obstacles and to leverage facilitators.

Tenecteplase-associated orolingual angioedema: A case report and literature review.

PURPOSE: Orolingual angioedema (OA) secondary to administration of thrombolytic therapy is a rare, but serious, known adverse effect. Despite the lack of robust evidence for their use, C1 esterase inhibitors are recommended by guidelines for the treatment of refractory thrombolytic-associated OA. This report highlights the use of a C1 esterase inhibitor in a patient with tenecteplase-associated OA unresolved by antihistamine and corticosteroid therapy. SUMMARY: A 67-year-old white male with a history of hypertension managed with lisinopril presented to the emergency department with acute onset of slurred speech and left-sided hemiparesis. Following workup, an outside hospital's neurology stroke team suspected an acute infarct and determined the patient to be a candidate for tenecteplase. Approximately 1 hour after tenecteplase administration, the patient began complaining of dyspnea and mild oral angioedema. Immediate interventions for OA management included intravenous therapy with dexamethasone 10 mg, diphenhydramine 25 mg, and famotidine 20 mg. After an additional 30 minutes, the patient's OA symptoms continued to progress and a C1 esterase inhibitor (Berinert) was administered. Shortly after administration of the C1 esterase inhibitor, the patient's symptoms continued to worsen, ultimately leading to endotracheal intubation. Following intubation, symptom improvement was noted, and the patient was safely extubated after 30 hours. CONCLUSION: Although rare, OA is a potentially life-threatening complication of tenecteplase therapy and requires prompt pharmacological intervention to optimize patient outcomes. Currently, no single agent or treatment algorithm exists that has shown significant efficacy or safety in the setting of thrombolytic-associated OA. Until data are available for C1 esterase inhibitors in this application, these inhibitors should only be considered if there is continued symptom progression after intravenous administration of corticosteroids and antihistamines.