Efficacy Of Tenecteplase Research Articles

Tenecteplase Versus Alteplase in Medium Vessel Occlusion Ischemic Stroke: A Secondary Analysis of the Alteplase Compared to Tenecteplase Randomized Trial.

The safety and efficacy of tenecteplase in patients with ischemic stroke due to medium vessel occlusion (MeVO) are not well studied. We aimed to compare tenecteplase with alteplase in stroke due to MeVO. Patients with baseline M2-middle cerebral artery (MCA), M3/M4-MCA, P2/P3/P4-posterior cerebral artery (PCA), A2/A3/A4-anterior cerebral artery (ACA) occlusions from the Alteplase Compared to Tenecteplase (AcT) trial were included. Primary outcome was the proportion of 90-day modified Rankin Scale (mRS) 0-1. Secondary outcomes were 90-day mRS 0-2, ordinal mRS, mortality, quality of life measures (EuroQol 5-Dimension 5-Level, EuroQol visual analog scale), and symptomatic intracerebral hemorrhage (sICH). Initial and final successful reperfusion were reported in patients undergoing endovascular thrombectomy (EVT). Among 1,558 patients with available baseline computed tomography angiography; 455 (29.2%) had MeVO of which 27.5% (125/455) were proximal M2; 16.3% (74/455) were distal M2; 35.2% (160/455) were M3/M4; 7.5% (34/455) were A2/A3/A4; and 13.6% (62/455) were P2/P3/P4 occlusions. EVT was performed in 87/455 (19.1%) patients. mRS 0-1 at 90 days was achieved in 37.9% in the tenecteplase versus 34.7% in the alteplase group (adjusted risk ratio [aRR] 1.07; 95% confidence interval [CI] 0.91-1.25). Rates of 90-day mRS 0-2, sICH, and mortality were similar in both groups. No statistical difference was noted in initial successful reperfusion rates (13.0% vs. 7.5%) among the 87 patients who underwent endovascular thrombectomy. However, final successful reperfusion was higher in the tenecteplase group (71.7% vs. 60.0%, aRR 1.29, 95% CI 1.04-1.61). Intravenous tenecteplase had comparable safety, functional outcomes and quality of life compared to intravenous alteplase among patients with MeVO. Among those treated with EVT, tenecteplase was associated with higher successful reperfusion rates than alteplase.

Efficacy of tenecteplase vs alteplase for the treatment of patients with acute ischemic stroke: A systematic review and meta-analysis

Efficacy of tenecteplase vs alteplase for the treatment of patients with acute ischemic stroke: A systematic review and meta-analysis

Characteristics and predictors of stroke mimics in young patients in the norwegian tenecteplase stroke trial (NOR-TEST)

BackgroundSeveral studies have shown that stroke mimics occur more often among young patients. Our aims were to identify the common mimics in young patients under the age of 60 years who received thrombolysis, to analyze the risk of hemorrhage after treatment with thrombolysis, and to identify risk factors and clinical parameters that might identify mimics in this group.MethodsNorwegian Tenecteplase Stroke Trial was a phase-3 trial investigating safety and efficacy of tenecteplase vs. alteplase in patients with acute ischemic stroke. Patients diagnosed with either acute cerebral ischemia or transient ischemic attack were categorized as stroke group, and patients with any diagnosis other than ischemic stroke or transient ischemic attack as mimics group. Patients were grouped post-hoc into young (< 60 years) and old (≥ 60 years). Logistic regression analyses were performed with mimics vs. stroke as dependent variable to identify predictors of mimics.ResultsOf the 1091 patients included in the trial, 211 patients (19.3%) were under the age of 60 years. Out of the 1091 patients, 434 (39.8%) were female, median age 77 years (18–99 years), and median NIHSS was 4. Sixty-nine patients (32.7%) out of the 211 patients under the age of 60 were diagnosed as mimic. Mimics were significantly more frequent among the young (OR = 3.3, 32.7% vs. 12.8%, p = < 0.001). The most frequent mimics diagnoses among patients under 60 years of age were migraine (11.8%), no definite diagnosis (11.4%) and peripheral vertigo (3.3%). Mimics were independently associated with age < 50 years (OR = 4.97, p = < 0.001), not currently working/studying (OR = 3.38, p = 0.002) and not having aphasia on admission (OR = 2.95, p = 0.025). None of the mimics under the age of 60 years had symptomatic or asymptomatic intracerebral hemorrhage as a complication to thrombolysis.ConclusionWe found significantly more mimics in the young, of which migraine was the most predominant diagnosis. Thrombolysis with alteplase or tenecteplase did not cause ICH in any mimics under 60 years.

Efficacy and Safety of Injection Tenecteplase in 4.5 to 24 hours imaging eligible window patients with Acute Ischemic Stroke (EAST-AIS) (P7-5.016)

<h3>Objective:</h3> To determine the efficacy and safety of injection Tenecteplase along with standard treatment in acute ischemic stroke with or without large vessel occlusion presenting within 4.5 to 24 hours of onset <h3>Background:</h3> Currently in Acute Ischemic stroke (AIS) patients, intravenous thrombolysis is approved for the 0-to-4.5-hour window period and mechanical thrombectomy for large vessel occlusion up to 24 hours of stroke onset in eligible patients. Previous studies have evaluated the safety and efficacy of Tenectplasse in a small number of patients in the period beyond 4.5hours of stroke onset. In the present study, we evaluate the safety and efficacy of injction of Tenectplase in AIS patients (with or without large vessel occlusion) in the time window 4.5 to 24 hours of stroke onset. <h3>Design/Methods:</h3> Patients will be enrolled primarily based on imaging the eligibility criteria with a perfusion lesion-ischemic core mismatch greater than1.8 between the volume of hypoperfusion and the volume of the ischemic core, with the absolute difference in volume being greater than 10 ml, and ischemic-core volume less than 70 ml. Additional inclusion criteria are patients age should be &gt; 18 years, onset period between 4.5 to 24 hours with NIHSS&gt;5, and pre-stroke Mrs value of 2 or less. A total of one hundred patients are planned to be enrolled, 50 each in Tenectlase are (cases-0.25mg/kg; maximum 25mg) and placebo arm (controls) in a ratio of 1:1 administered as a singlr bolus injection. An independent data safety and monitoring board (DSMB) will share responsibility for regular oversight of patient safety during the study. <h3>Results:</h3> This is ongoing randomized control trial. <h3>Conclusions:</h3> The study is an investigator initiated prospective and randomized controlled trial design. The safety endpoints along with efficacy of Tenecteplase using the modified Ranking Scale (mRS) score at 90 days of stroke onset will be determined. <b>Disclosure:</b> Dr. Jatwani has nothing to disclose. Awadh K. Pandit has nothing to disclose. Ms. Tangri has nothing to disclose. Dr. Srivastava has nothing to disclose. Dr. Bhatia has nothing to disclose. Ajay Garg has nothing to disclose. Dr. Vibha has nothing to disclose. Vishnu VY has nothing to disclose. Dr. Das has nothing to disclose. Divya MR has nothing to disclose.

Replacing Alteplase with Tenecteplase: Is the Time Ripe?

Thrombolysis for acute ischemic stroke has predominantly been with alteplase for over a quarter of a century. In recent years, with trials showing evidence of higher rates of successful reperfusion, similar safety profile and efficacy of tenecteplase (TNK) as compared to alteplase, TNK has now emerged as another potential choice for thrombolysis in acute ischemic stroke. In this review, we will focus on these recent advances, aiming: (1) to provide a brief overview of thrombolysis in stroke; (2) to provide comparisons between alteplase and TNK for clinical, imaging, and safety outcomes; (3) to focus on key subgroups of interest to understand if there is an advantage of using TNK over alteplase or vice-versa, to review available evidence on role of TNK in intra-arterial thrombolysis, as bridging therapy and in mobile stroke units; and (4) to summarize what to expect in the near future from recently completed trials and propose areas for future research on this evolving topic. We present compelling data from several trials regarding the safety and efficacy of TNK in acute ischemic stroke along with completed yet unpublished trials that will help provide insight into these unanswered questions.

Tenecteplase vs. alteplase for treatment of acute ischemic stroke: A systematic review and meta-analysis of randomized trials.

Several randomized controlled trials (RCTs) have compared tenecteplase to alteplase for treatment of acute ischemic stroke (AIS). Yet, there is no meta-analysis that includes the latest published RCTs of 2022. We sought to compare the safety and efficacy of tenecteplase vs. alteplase for the treatment of AIS through a meta-analysis of all published RCTs. A systematic literature review of the English language literature was conducted using PubMed, Web of Science, Scopus, and Embase. We included RCTs that focused on patients with AIS treated with tenecteplase and alteplase. Multiple reviewers screened through potential studies to identify the final papers included in our analysis. Following PRISMA guidelines, multiple authors extracted data to ensure accuracy. Data were pooled using a random-effects model. Nine trials, with 3,706 patients, compared outcomes of patients treated with tenecteplase and alteplase for AIS. Both treatments resulted in comparable rates of modified Rankin Scale (mRS) 0-1 at 90 days (RR = 1.03; 95% CI = 0.97-1.10; P-value = 0.359) and mRS 0-2 at 90 days (RR = 1.03; 95% CI = 0.87-1.22; P-value = 0.749). There was no heterogeneity among included studies regarding mRS 0-1 rates (I2 = 26%; P-value = 0.211); however, there was significant heterogeneity in mRS 0-2 rates (I2 = 71%; P-value = 0.002). Similarly, rates of mortality (RR = 0.97; 95% CI = 0.81-1.16; P-value = 0.746) and symptomatic intracranial hemorrhage (sICH) rates (RR = 1.10; 95% CI = 0.75-1.61; P-value = 0.622) were comparable in both treatment groups. There was no significant heterogeneity among included studies in either mortality (I2 = 30%; P-value = 0.181) or sICH (I2 = 0%; P-value = 0.734) rates. Further analysis comparing dosing of tenecteplase (0.1, 0.25, 0.32, and 0.4 mg/kg) yielded no significant differences for any of the endpoints (mRS 0-1, mRS 0-2, sICH, and mortality) compared to alteplase. Based on available evidence from completed RCTs, tenecteplase has proven similar safety and efficacy to alteplase for treatment of AIS.

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64). In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Comparative safety and efficacy of tenecteplase and streptokinase in prosthetic valve thrombosis: An observation from Eastern India

Prosthetic valve thrombosis (PVT) is a life-threatening emergency. Thrombolytic therapy is emerging as a potential substitute. The objective of this study was to assess the safety and efficacy of Tenecteplase (TNK) in comparison to streptokinase (STK) in patients with PVT. In this prospective study, patients with PVT who were not subjected to the surgery underwent thrombolysis with TNK (TNK arm) or STK (STK arm). Efficacy and safety of both treatment arms were judged from clinical, echocardiographic (ECHO), and Cinefluoroscopic parameters. Treatment outcomes and complications were compared between the two arms.Between December 2017 and December 2019, a total of 41 cases of PVT were enrolled to receive either TNK (n=23) or STK (n=18). After thrombolysis, complete recovery was significant in the TNK arm (82.6% [19/23] vs. 44.4% [8/18], respectively; p=0.007) irrespective of the valve position. This trend was observed in both mitral PVT (85.7% vs. 46.6%, respectively; p=0.03) and aortic PVT (77.8% vs. 33.3%, respectively; p=0.151). No failure was seen in the TNK arm but failure was observed in 1/3cases in the STK arm. No major bleeding was observed with either treatment. Minor bleeding and systemic embolization were non-significant (P=0.514). There were no deaths in the TNK arm but two patients (11%) from the STK arm died.To our knowledge, this is the largest published comparative evidence indicating superior efficacy and equal safety of tenecteplase compared to streptokinase for the treatment of prosthetic valve thrombosis irrespective of valve position and NYHA class.

Tenecteplase for Thrombolysis in Acute Ischemic Stroke and Its Outcome—An Indian Experience

Background: Stroke has been a growing concern with increasing morbidity and mortality worldwide. Tenecteplase has been approved in India as a newer thrombolytic, in acute ischemic stroke, since 2016. Very few studies have been reported to know the efficacy of Tenecteplase in AIS compared to alteplase. Aim: This study was done to understand the efficacy and related complications of Tenecteplase in AIS. Methods: In this prospective study, we took 112 people with AIS who received Tenecteplase, admitted between August 2018 and August 2020. After obtaining ethical approval, we tabulated patients’ data and did the statistical analysis using an unpaired t test, Analysis of Variance, and chi-square test. A P value of &lt;.05 using a 2-tailed test was considered significant for all statistical analyses. Results: Out of 112 patients, 67.9% were male and 32.1% were female, with a mean age of 60.7 years. We classified stroke by using the TOAST classification. About 62.5% are classified as large atherosclerotic type, 14.3% cardioembolic, and 17.0% lacunar strokes. A total of 82.1% had a middle cerebral artery region stroke. The mean door to needle time was 76.7 min with a standard deviation of 33.3. The primary outcome was met in 47.3%, and the secondary result was achieved in 59.8%. Intracerebral hematoma was the most commonly observed complication. Mortality accounted for 9.8% of the total population. Conclusions: Tenecteplase is the newer thrombolytic agent with good efficacy. More studies are needed globally to understand regional differences and effectiveness.

Abstract 44: Safety Of Tenecteplase And Alteplase In Tandem Lesion Stroke: A Pooled Analysis Of The Extend-IA TNK Trials

Introduction: The efficacy of tenecteplase (TNK) in patients with tandem lesions (TL) in the anterior circulation is unknown. The longer half-life of TNK could potentially lead to increased hemorrhage, especially in patients who require stenting of the extracranial internal carotid artery (eICA) and subsequent antiplatelet therapy. We assessed the efficacy and safety of TNK in a pooled analysis of the EXTEND-IA TNK trials. Methods: We compared the treatment effect of TNK (pooled analysis of 0.25 and 0.40mg/kg dosing) with alteplase (tPA), stratifying for TL presence. A TL was defined as a combination of eICA pathology (ipsilateral stenosis &gt;70% or occlusion) and intracranial LVO. Outcomes evaluated include 90-day mRS, intracranial reperfusion at initial angiographic assessment, mortality, ICH (symptomatic [sICH] and parenchymal hematoma [PH]). Treatment effect was adjusted for baseline NIHSS, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models. Results: Of 483 patients with an anterior circulation occlusion, 71/483 (15%) patients had a TL and 43/71 (61%) patients required eICA stenting. In TL patients, reperfusion at initial angiographic assessment was observed in 11/56 (20%) of patients treated with TNK vs. 1/15 (7%) patients treated with tPA (aOR:3.71; 95% CI:0.42-32.75). sICH was observed in 4/71(6%) TL vs 7/412 (2%) nonTL patients (p=0.04). Among TL patients, sICH occurred in 4/56 (7%) patients treated with TNK vs 0/15 (0%) tPA treated patients (p=0.57); sICH occurred in 2/40 (5%) of the 0.25mg/kg TNK group and 2/16 (12.5%) of the 0.40mg/kg TNK group. PH was observed in 6/56 (11%) patients treated with TNK vs 0/15 (0%) tPA treated patients (p=0.33). 90-day mRS (TNK median 2 vs. tPA median 4, acOR:1.21; 95% CI:0.42-3.48), mortality (TNK: 5 [9%] vs. tPA: 3 [20%], aOR:0.45; 95% CI:0.08-2.50), and eICA stenting (TNK: 35 [64%] vs. tPA: 8 [57%], p=0.65) rates did not differ between the two treatment groups. Conclusions: Although patients with TL in the anterior circulation were at higher risk of hemorrhagic complications, these did not significantly differ between the TNK and tPA groups. A numeric increase in bleeding with TNK was not accompanied by an increase in mortality or worse functional outcome.

Safety and Efficacy of Tenecteplase in Older Patients With Large Vessel Occlusion: A Pooled Analysis of the EXTEND-IA TNK Trials.

Detailed study of tenecteplase (TNK) in patients older than 80 years is limited. The objective of our study was to assess the safety and efficacy of TNK at 0.25 and 0.40 mg/kg doses in patients older than 80 years with large vessel occlusion. We performed a pooled analysis of the EXTEND-IA TNK randomized controlled trials (n = 502). Patients were adults presenting with ischemic stroke due to occlusion of the intracranial internal carotid, middle cerebral, or basilar artery presenting within 4.5 hours of symptom onset. We compared the treatment effect of TNK 0.25 mg/kg, TNK 0.40 mg/kg, and alteplase 0.90 mg/kg, stratifying for patient age (>80 years). Outcomes evaluated include 90-day modified Rankin Scale (mRS) score, all-cause mortality, and symptomatic ICH. Treatment effect was adjusted for baseline NIH Stroke Score, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models. In patients >80 years (n = 137), TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, adjusted common odds ratio (acOR) 2.70, 95% CI 1.23-5.94) and reduced mortality (acOR 0.34, 95% CI 0.13-0.91) vs 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, acOR 2.28, 95% CI 1.03-5.05) vs alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40 mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40 mg/kg, 1 patient treated with alteplase, and 0 patients treated with TNK 0.25 mg/kg. In patients ≤80 years, no differences in 90-day mRS, mortality, or symptomatic ICH were observed among TNK 0.25 mg/kg, alteplase, and TNK 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS and lower mortality in patients older than 80 years. No differences among the doses were observed in younger patients. NCT02388061, NCT03340493. This study provides Class II evidence that tenecteplase 0.25 mg/kg given before endovascular therapy in patients >80 years old with large vessel occlusion stroke is associated with better functional outcomes at 90 days and reduced mortality when compared to tenecteplase 0.40 mg/kg or alteplase 0.90 mg/kg.

Editors' Note: Multimodal CT or MRI for IV Thrombolysis in Ischemic Stroke With Unknown Time of Onset

In their retrospective analysis of 184 patients treated with intravenous thrombolysis for an unknown time of stroke onset, Macha et al. compared treatment times and outcomes based on assessment using multimodal computed tomography (CT) or magnetic resonance imaging (MRI). Unsurprisingly, patients selected for thrombolysis based on CT were treated more quickly than those who underwent brain MRI (mean difference 28 minutes); however, there were no significant differences in the rate of symptomatic intracranial hemorrhage or favorable outcome at 90 days between the imaging groups. Kumar and Singh comment that MRI has other advantages, such as the detection of microhemorrhages, higher spatial resolution for brain injury, lack of intravenous contrast requirement, and more rapid imaging acquisition with recent technological advancements. The investigators agree that MRI offers unique advantages over CT; however, these advantages are outweighed by the more expedient delivery of acute stroke care with CT, as has been confirmed in the recent EXTEND trial. Both the investigators and the commenters share optimism about the use of tenecteplase over alteplase as a means of shortening treatment delays; however, the safety and efficacy of tenecteplase beyond 4.5 hours (or in the unknown time window) have not yet been established. In their retrospective analysis of 184 patients treated with intravenous thrombolysis for an unknown time of stroke onset, Macha et al. compared treatment times and outcomes based on assessment using multimodal computed tomography (CT) or magnetic resonance imaging (MRI). Unsurprisingly, patients selected for thrombolysis based on CT were treated more quickly than those who underwent brain MRI (mean difference 28 minutes); however, there were no significant differences in the rate of symptomatic intracranial hemorrhage or favorable outcome at 90 days between the imaging groups. Kumar and Singh comment that MRI has other advantages, such as the detection of microhemorrhages, higher spatial resolution for brain injury, lack of intravenous contrast requirement, and more rapid imaging acquisition with recent technological advancements. The investigators agree that MRI offers unique advantages over CT; however, these advantages are outweighed by the more expedient delivery of acute stroke care with CT, as has been confirmed in the recent EXTEND trial. Both the investigators and the commenters share optimism about the use of tenecteplase over alteplase as a means of shortening treatment delays; however, the safety and efficacy of tenecteplase beyond 4.5 hours (or in the unknown time window) have not yet been established.

Real-world comparative safety and efficacy of tenecteplase versus alteplase in acute ischemic stroke patients with large vessel occlusion.

Background and aims:Tenecteplase has recently emerged as an alternative thrombolytic agent in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO), possibly superior in achieving early reperfusion compared with alteplase. We aimed to compare the safety and efficacy of intravenous tenecteplase with intravenous alteplase for AIS patients with LVO in everyday clinical practice settings.Methods:We prospectively evaluated patients with AIS due to LVO, treated with intravenous thrombolysis (IVT) with or without mechanical thrombectomy in two tertiary stroke centers. Patients were treated with standard-dose alteplase (0.9 mg/kg) or 0.25 mg/kg tenecteplase. Safety outcomes included prevalence of symptomatic intracranial hemorrhage (sICH) and mortality. Efficacy outcomes included averted thrombectomy, major neurological improvement at 24 h (defined as decrease in baseline NIHSS score of 8 points or greater) and functional status on discharge and on 3 months assessed by modified Rankin Scale (mRS).Results:Nineteen AIS patients with LVO received tenecteplase and 39 received alteplase. We observed a non-significant higher rate of averted thrombectomies (32% versus 18%, p = 0.243) and a non-significant higher rate of sICH (16% versus 5%, p = 0.201) in the tenecteplase group. The rate of 24 h major neurological improvement was higher in the tenecteplase group (64% versus 33%, p = 0.046) but this was marginally attenuated in multivariable analyses (adjusted OR 10.22, 95% CI: 0.73–142.98; p = 0.084). Discharge mRS, 3-months mRS, and 3-month functional independence (mRS scores of 0–2) did not differ (p > 0.2) between the two groups. The rates of 3-month mortality (11% versus 18%, p = 0.703) were similar in the two groups. No independent association between thrombolytic agent and safety or efficacy outcomes emerged in multivariable regression analyses.Conclusion:The present pilot observational study highlights that AIS patients with LVO treated with 0.25 mg/kg bolus administration of tenecteplase had increased likelihood to achieve early neurological improvement compared with AIS patients treated with alteplase, but this association was attenuated after adjustment for potential confounders. There were no significant differences in 3-month functional or safety outcomes between the two groups. This preliminary real-world observation requires independent confirmation in larger, multicenter studies.

Tenecteplase for Acute Ischemic Stroke: Current Evidence and Practical Considerations

Tenecteplase offers pharmacological advantages over alteplase, and growing evidence supports its consideration for the treatment of patients with acute ischemic stroke. Its ease of administration as a single bolus makes it a preferable agent for patients who need to be urgently transported to a comprehensive stroke center for endovascular therapy (drip and ship) and for patients first evaluated at comprehensive stroke centers who are eligible for endovascular intervention (combined intravenous and endovascular approach). Recent randomized controlled trials indicated that the efficacy of tenecteplase may be similar to that of alteplase in patients with mild strokes and that it is superior to alteplase for patients with more severe strokes from a large vessel occlusion. Cumulative evidence currently favors the use of the 0.25mg/kg dose. While tenecteplase has not been approved by regulatory agencies in the USA or the EU for the treatment of acute ischemic stroke, ongoing trials and additional clinical experience from countries where it is already being used in practice will likely clarify the role of tenecteplase for the acute management of ischemic stroke in the near future.

Safety and predictors of stroke mimics in The Norwegian Tenecteplase Stroke Trial (NOR-TEST)

Stroke mimics are frequently treated with thrombolysis in clinical practice and thrombolytic trials. Although alteplase in stroke mimics has proven to be safe, safety of tenecteplase in stroke mimics has not been assessed in an ischemic stroke study setting. We aimed to assess clinical characteristics and safety of stroke mimics treated with thrombolysis in the Norwegian Tenecteplase Stroke Trial. We also aimed to identify possible predictors of stroke mimics as compared to patients with acute cerebral ischemia. Norwegian Tenecteplase Stroke Trial was a phase-3 trial investigating safety and efficacy of tenecteplase vs. alteplase in patients with suspected acute cerebral ischemia. Two groups were defined based on diagnose at discharge: patients with a different diagnose than ischemic stroke or transient ischemic attack (stroke mimics group) and patients diagnosed with ischemic stroke or transient ischemic attack (acute cerebral ischemia group). Logistic regression analyses were performed with stroke mimics vs. acute cerebral ischemia as dependent variable to identify predictors of stroke mimics. Of 1091 randomized patients, 181 (16.6%) were stroke mimics. Migraine (22.2%) and peripheral vertigo (11.4%) were the two most frequent stroke mimic-diagnoses. There was no symptomatic intracerebral hemorrhage in the stroke mimics group. Stroke mimics were independently associated with age ≤60 years (OR 2.75, p < 0.001), female sex (OR 1.48, p = 0.026), no history of myocardial infarction (OR 2.03, p = 0.045), systolic BP ≤ 150 mmHg (OR 2.33, p < 0.001), NIHSS ≤ 6 points (OR 1.83, p = 0.011), sensory loss (OR 1.55, p = 0.015), and no facial paresis (OR 2.41, p < 0.001) on admission. Thrombolysis with tenecteplase seems to be as safe as with alteplase in stroke mimics. Predictors were identified for stroke mimics which may contribute to differentiate stroke mimics from acute cerebral ischemia in future stroke trials.

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.

An unusual presentation of massive pulmonary embolism mimicking septal acute myocardial infarction treated with tenecteplase

A 31-year-old man (175 cm, 82 kg) was referred to the emergency department 2 h after the sudden onset of acute dyspnea. Immediate ECG showed sinus tachycardia with ST elevations from V1 through V2 and a diagnosis of septal acute myocardial infarction was made. ECG on admission to the cardiology department showed the same results plus the S1-Q3-T3 pattern. Echocardiogram revealed a normally contracting left ventricle, a distended right ventricle with free wall hypokinesia and displacement of the interventricular septum towards the left ventricle. Thrombolytic therapy with tenecteplase 8000 IU and heparin 5000 IU was administered 5-10 min after hospitalisation and the patient was haemodynamically stable 30 min later. Echocardiogram performed 12 h after thrombolysis showed a normal left ventricle and a less distended right ventricle. Lung spiral computed tomography (CT) and lower abdominal CT on the fourth day showed large emboli in the inferior pulmonary arteries of the right and left lung. Rarely, massive pulmonary embolism may mimic anteroseptal acute myocardial infarction on ECG and this case demonstrates the utility of echocardiography for a differential diagnosis, as well as the efficacy of tenecteplase for thrombolytic therapy.

Novel Thrombolytic Drugs

Treatment of acute ischaemic stroke aims to recanalize the occluded artery, salvage the at-risk brain tissue and thus minimize neurological sequelae. Efforts a decade ago have led to the only currently approved medical treatment for acute ischaemic stroke, i.e. intravenous alteplase given within 3 hours of stroke onset. Recanalization occurs in only one-half of the patients receiving alteplase, and only approximately 5% of all ischaemic stroke patients in industrialized countries receive this treatment. Studies are currently being carried out to determine whether intravenous alteplase would be safe and effective for up to 4.5 hours after ischaemic stroke onset, and whether it should be followed by an intra-arterial approach. Two novel thrombolytic drugs being studied for acute ischaemic stroke are desmoteplase and tenecteplase. Although the first trials were promising, the most recent evidence suggests that desmoteplase is not superior to placebo, even in carefully selected patients, in the 3- to 9-hour time window after stroke onset. Tenecteplase has only been studied for acute ischaemic stroke in a single noncontrolled, dose-finding trial in the 3-hour time window after stroke onset, which suggested a similar efficacy to that demonstrated in the historical data from the alteplase trials. A trial to compare the safety and efficacy of tenecteplase versus alteplase is ongoing. Safer and more effective thrombolytic drugs for the treatment of ischaemic stroke are thus being sought. Such agents will be welcome, but they are not here yet. While waiting we are likely to see the emergence of additive therapies, including ultrasound insonation, neuroprotective/regenerative agents and invasive intra-arterial techniques. Novel thrombolytic drugs, or other novel therapies, possess great potential to make a difference in the future, but the most urgent priority now is in the organization of stroke treatment in such a way that more patients receive the currently available optimal treatments.

Efficacy of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: one-year follow-up results of the assessment of the safety of a new thrombolytic-3 (ASSENT-3) randomized trial in acute myocardial infarction

Background In the ASsessment of the Safety of a New Thrombolytic 3 (ASSENT-3) study, full-dose tenecteplase plus enoxaparin or half-dose tenecteplase plus abciximab reduced the frequency of ischemic complications of acute myocardial infarction, when compared to full-dose tenecteplase plus unfractionated heparin. The aim of the present study was to determine the effect of these fibrinolytic regimens on 1-year mortality. Methods and results Vital status at 1 year was available for 5942 patients (97.5%) of the 6095 initially enrolled in the study. At 1 year, 515 patients (8.7%) had died. Elderly or female patients and patients with low body weight, previous myocardial infarction, anterior wall myocardial infarction, and diabetes were at increased risk for death at 1 year. Mortality at 1 year was 7.9 % (n = 161) in the heparin group, 8.1% (n = 166) in the enoxaparin group, and 9.3% (n = 188) in the abciximab group ( P = .226). Overall, pairwise comparisons did not show a significant difference among treatment regimens: relative risk 1.03 (95% CI 0.82–1.30) for enoxaparin versus heparin ( P = .794) and relative risk 1.18 (95% CI 0.95–1.47) for abciximab versus heparin ( P = .144). However, 1-year outcome tended to be worse with abciximab in diabetic patients. Conclusion Mortality at 1 year after acute myocardial infarction remains high. Despite a reduction in ischemic complications after acute myocardial infarction with the use of full-dose tenecteplase plus enoxaparin or half-dose tenecteplase plus abciximab, mortality at 1 year was similar in these treatment groups.

Safety and efficacy of tenecteplase in acute myocardial infarction

The use of intravenous thrombolytic agents has revolutionised the treatment of acute myocardial infarction. However, the improved mortality achieved with these drugs is tempered by the risk of serious bleeding complications, especially intracranial haemorrhage (ICH). Tenecteplase (TNKase™, Genetech Inc.) is an engineered variant of alteplase (Activase®, Genentech Inc.) designed to have increased fibrin specificity, greater efficacy and a longer half-life. The longer half-life of tenecteplase compared to alteplase allows for convenient single bolus administration of the drug. In addition, tenecteplase dosing is based on actual or estimated patient weight, which enhances both the safety and efficacy outcomes. Large clinical trials have demonstrated equivalence in mortality and ICH between tenecteplase and alteplase. Compared to alteplase, tenecteplase use leads to lower rates of bleeding complications and a decreased risk of ICH among low weight, elderly women.