Comparación entre tenecteplase y alteplase en la trombolisis intravenosa del ataque cerebrovascular isquémico

Introducción: la trombolisis intravenosa es parte fundamental del tratamiento agudo de los pacientes que sufren un ataque cerebrovascular (ACV) isquémico. Existe un interés creciente en la utilización de tenecteplase como alternativa trombolítica a alteplase. El objetivo del presente trabajo es comparar la efectividad clínica de tenecteplase respecto a alteplase en la trombolisis intravenosa del ACV isquémico. Método: estudio de cohorte, bispectivo y unicéntrico, de todos los pacientes ingresados con ACV isquémico y que recibieron trombolíticos intravenosos, desde 2019 a 2022. Se compararon prospectivamente los pacientes tratados con tenecteplase con aquellos tratados con alteplase como control histórico. Se realizó test de chi cuadrado o exacto de Fisher para la asociación de variables categóricas y prueba de Wilcoxon para la comparación de medianas. Se consideró significativo un valor p menor de 0,05. Resultados: se incluyeron 69 pacientes (33 recibieron alteplase y 36 tenecteplase). La mediana de la escala de NIHSS fue de 11 (RIC 8-18) y del tiempo inicio de síntomas-aguja de 160 minutos (RIC 120-208). No se hallaron diferencias estadísticamente significatvas entre los puntajes de las escalas de coma de Glasgow y NIHSS al egreso hospitalario, así como en la escala de Rankin modificada (mRS) 0-2 y mortalidad a los seis meses, entre los dos grupos de pacientes. Tampoco hubo diferencias en las complicaciones hemorrágicas intracraneanas entre ambos grupos (13,9% para tenecteplase y 12,1% para alteplase). Conclusiones: se presenta el primer estudio acerca del tema en nuestro medio. En concordancia con los recientes ensayos internacionales, el presente trabajo no mostró diferencias significativas en los resultados clínicos de los pacientes tratados con tenecteplase o alteplase. El tenecteplase podría ser una alternativa razonable a alteplase como terapia trombolítica en el ACV isquémico, con una buena relación costo-beneficio y forma de implementación más sencilla. Se necesitan estudios aleatorizados y con un mayor número de pacientes.

Introduction: intravenous thrombolysis is a key part of the acute treatment of patients with ischemic stroke. There is a growing interest in the use of tenecteplase as a thrombolytic alternative to alteplase. The aim of this study is to compare the clinical effectiveness of tenecteplase versus alteplase in intravenous thrombolysis for ischemic stroke. Method: a single-center, bispective cohort study of all patients admitted with ischemic stroke who received intravenous thrombolytics from 2019 to 2022. Patients treated with tenecteplase were prospectively compared with those treated with alteplase as a historical control. Chi-square or Fisher's exact test was used for the association of categorical variables, and the Wilcoxon test was used for median comparison A p-value of less than 0.05 was considered significant. Results: a total of 69 patients were included in the study (33 received alteplase and 36 received tenecteplase). The median NIHSS scale score was 11 (IQR 8-18), and the median time from symptom onset to needle was 160 minutes (IQR 120-208). No statistically significant differences were found between Glasgow Coma Scale and NIHSS scores at hospital discharge, as well as in modified Rankin Scale (mRS) 0-2 and mortality at 6 months, between the two groups of patients. There were also no differences in intracranial hemorrhagic complications between both groups (13.9% for tenecteplase and 12.1% for alteplase). Conclusions: This is the first study on the topic in our setting. In line with recent international trials, our study did not show significant differences in clinical outcomes of patients treated with tenecteplase or alteplase. Tenecteplase could be a reasonable alternative to alteplase as thrombolytic therapy in ischemic stroke, with a good cost-benefit ratio and simpler implementation. Randomized studies with a larger number of patients are needed.

Introdução: A trombólise intravenosa é uma parte essencial do tratamento agudo de pacientes que sofrem um acidente vascular cerebral isquêmico. Há um interesse crescente no uso da tenecteplase como uma alternativa trombolítica à alteplase. O objetivo deste estudo foi comparar a eficácia clínica da tenecteplase com a alteplase na trombólise intravenosa do AVC isquêmico. Métodos: estudo de coorte, bispectivo, em um único centro, de todos os pacientes admitidos com AVC isquêmico que receberam trombolíticos intravenosos de 2019 a 2022. Os pacientes tratados com tenecteplase foram comparados prospectivamente com aqueles tratados com alteplase como um controle histórico. O teste de qui-quadrado ou exato de Fisher foi realizado para a associação de variáveis categóricas e o teste de Wilcoxon para a comparação de medianas. Um valor de p inferior a 0,05 foi considerado significativo. Resultados: Foram incluídos 69 pacientes (33 receberam alteplase e 36 tenecteplase). A mediana do escore da escala NHISS foi de 11 (RIC 8-18) e a mediana do tempo de início dos sintomas foi de 160 minutos (RIC 120-208). Não foram encontradas diferenças estatisticamente significativas entre os escores de coma de Glasgow e NIHSS na alta hospitalar, bem como na Escala de Rankin modificada (MRS) 0-2 e na mortalidade em 6 meses, entre os dois grupos de pacientes. Também não houve diferenças nas complicações hemorrágicas intracranianas entre os dois grupos (13,9% para tenecteplase e 12,1% para alteplase). Conclusões: Este é o primeiro estudo sobre o assunto em nosso meio. De acordo com estudos internacionais recentes, nosso estudo não mostrou diferenças significativas nos resultados clínicos em pacientes tratados com tenecteplase ou alteplase. A tenecteplase poderia ser uma alternativa razoável à alteplase como terapia trombolítica no AVC isquêmico, com uma boa relação custo-benefício e implementação mais fácil. São necessários estudos randomizados com um número maior de pacientes.

Efficacy and safety of tenecteplase in the treatment of acute ischemic stroke：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of intravenous bolus of tenecteplase in the treatment of acute ischemic stroke （AIS）， in order to provide evidence-based support for the clinic’s choice of intravenous thrombolytic drugs. METHODS Randomized controlled trials （RCTs） about the efficacy and safety of tenecteplase versus alteplase （control） in the treatment of AIS were collected from PubMed， Embase， the Cochrane Library， Web of Science， Sinomed， CNKI， Wanfang Data， and VIP during the inception to June 2022. Two evaluators independently screened the literature， extracted data from the literature， assessed the bias risk of included study， and then conduct meta-analysis by using Stata 15 software. RESULTS A total of 8 literature were included， involving 2 129 patients. Meta-analysis results showed that the early improvement rate of neurological function [OR（95%CI）＝2.44（1.09，5.46），P＝0.030] and the good rate of neurological function recovery （modified Rankin scale score 0-2 after 90 days of intravenous thrombolysis treatment） [OR（95%CI）＝1.54（1.00，2.36），P＝0.048] were higher in 0.25 mg/kg tenecteplase group （medium dose） than alteplase group. According to meta-analysis of other outcome indicators （including recanalization rate， percentage of reperfusion lesions， excellent rate of neurological function recovery， the incidence rate of bleeding， the incidence rate of symptomatic intraventricular hemorrhage and all-cause mortality rate within 90 d）， the tenecteplase group had no statistically significant difference with alteplase group （P＞0.05）. CONCLUSIONS Compared with alteplase， medium dose of tenecteplase has some advantages in terms of early neurological function improvement and neurological function recovery， and it does not increase the risk of adverse events.

Eficacia de tenecteplase comparada con alteplase para tratamiento de ictus isquémico agudo. Una revisión narrativa

Introducción: La trombólisis intravenosa con Alteplase (ALT) se recomienda como tratamiento estándar siendo el único agente trombolítico aprobado por la FDA, en infarto cerebral. La Tenecteplase (TNK), un activador tisular del plasminógeno modificado, surge como agente antitrombótico alternativo. Esta revisión narrativa evalúa la evidencia actual y aborda los problemas prácticos sobre la eficacia y seguridad de tenecteplase en comparación con alteplase. Metodología: Se realizó una búsqueda sistemática y analítica de la literatura, y se proporcionó una síntesis cualitativa de metaanálisis y ensayos clínicos concluidos, que compararon la efectividad y seguridad de la tenecteplase con alteplase en el AIS, utilizando artículos indexados en MEDLINE, Cochrane Library y Scopus. Resultados: Los ensayos clínicos aleatorizados en su mayoría coinciden al encontrar que TNK es al menos tan o más efectiva que la ALT para mejoría neurológica después del AIS; mientras los metaanálisis coinciden en que los pacientes que recibieron TNK presentaron una mayor recanalización exitosa, pero difieren en cuanto a los hallazgos de mejoría neurológica temprana, resultado funcional a los 90 días y mortalidad a los 90 días. Conclusión: La tenecteplase es al menos tan eficaz como la Alteplase con respecto a la mejoría neurológica después del tratamiento del accidente cerebrovascular isquémico agudo.

Introduction: Intravenous thrombolysis with alteplase (ALT) is recommended as standard treatment, being the only thrombolytic agent approved by the FDA. Tenecteplase (TNK), a modified tissue plasminogen activator, is emerging as an alternative antithrombotic agent. This narrative review assesses the current evidence and addresses practical issues regarding the efficacy and safety of tenecteplase compared to alteplase. Methodology: A systematic and analytical search of the literature was performed, providing a qualitative synthesis of meta-analyses and completed clinical trials comparing the effectiveness and safety of tenecteplase with alteplase in AIS, using articles indexed in MEDLINE, the Cochrane Library, and Scopus. Results: Randomized clinical trials mostly agree in finding TNK to be at least as or more effective than ALT for neurological improvement after AIS; while the meta-analyses agree that patients who received TNK had more successful recanalization, they differ in terms of the findings of early neurological improvement, functional outcome at 90 days, and mortality at 90 days. Conclusion: Tenecteplase is at least as effective as alteplase with regard to neurological improvement after treatment of acute ischemic stroke.

Trombolisis endovenosa con tenecteplase en ventana extendida tras selección por CT y AngioCT: Caso clínico / Thrombolysis with Tenecteplase in a stroke with a long time window after onset of symptoms. Report of one case

We report a 78-year-old man with a basal Rankin score of 2 points, last seen 10 hours before in good conditions, who arrived at the emergency department with left hemiparesis, hypoesthesia, and spacial neglect. Neuroimaging was compatible with stroke in the territory of the right middle cerebral artery. Due to the evolution time of the stroke, usual thrombolysis was contraindicated. Therefore, a thrombolysis with Tenecteplase was used with reversal of symptoms without symptomatic bleeding and with recovery of baseline functionality.

Systemic thrombolysis with tenecteplase in stent thrombosis patients as a life saving measure in odd situations: an observational study from tertiary care hospital

Background: Coronary artery stent thrombosis specifically acute stent thrombosis is always a nightmare for interventionist. Stent thrombosis is one of a severe and catastrophic complication of percutaneous coronary intervention (PCI). Repeat PCI is commonly considered the preferred strategy to manage patients with stent thrombosis. Thrombolytic therapy is considered only partially effective.Methods: This was a single centre largest ever observational study on this topic comprising of total 110 patients with history of previous stent implantation and now presented with an acute ST segment elevation myocardial infarction due to a probable stent thrombosis successfully treated with systemic thrombolysis with tenecteplase were studied over the period of 2 years (April 2017 to March 2019).Results: On analyzing data clinical success was reported in 92 (83.6%) patients, electrocardiographic success is seen in 102 (92.7%) patients while angiographic success was reported in 80(72.7%) patients. Cerebrovascular accident were reported in 2 (1.8%) patients which died later on.Conclusions: This study which is the first ever largest observational study on this topic demonstrates that, in patients with probable stent thrombosis and a short time to reperfusion in some specific extraordinary situations where timely percutaneous coronary intervention is not possible, systemic thrombolysis by fibrin specific Tenecteplase can be done as a life saving procedure which is associated with good immediate results.

New-onset unprovoked seizures in a cohort of children in South India: Application of the new ILAE 2014 definition of epilepsy

@#The Indian data comparing the efficacy and safety outcomes of tenecteplase and alteplase in acute ischemic stroke is scarce. We aimed to compare the outcomes of two agents in an Indian population. Methods: TENVALT study was a single centre, retrospective study. Patients aged 18 years or older with acute ischemic stroke were included in this study if they presented within 3 hours of symptom onset and had a deficit with National Institute of Health Stroke Scale (NIHSS) score > 4, had a modified Rankin score (mRS) of 2 or less before the stroke onset and had no evidence of hemorrhage on non-contrast computed tomography of brain. A good functional recovery (mRS score of 0-2) at the end of three months was defined as the primary efficacy outcome. The development of symptomatic intracerebral hemorrhage was considered as the primary safety outcome. Results: A total of 120 patients (alteplase, n=65; tenecteplase, n=55) underwent stroke thrombolysis during this study. The mean age of the presentation in tenecteplase group was 66.6 years and in alteplase group was 62.5 years. Most of the study subjects were males in both the groups (tenecteplase, 78.2%; alteplase, 61.5%). Hypertension was the most common comorbidity in both the groups (tenecteplase, 67.3%; alteplase, 76.9%). Median mRS score at 3 months of follow up was 2 in tenecteplase and 1 in alteplase group; however, the difference between the total number of patients having good functional recovery (mRS 0-2) in the two groups was not statistically significant (tenecteplase 74.5 vs alteplase 87.7%, P=0.09). The total number of patients who had symptomatic intracranial hemorrhage was comparable between the two groups (tenecteplase, 5.5%; alteplase, 6.2%).

Tenecteplase versus streptokinase thrombolytic therapy in patients with mitral prosthetic valve thrombosis

Objective Prosthetic valve thrombosis (PVT) is a dreadful complication of mechanical prosthetic valves. Thrombolytic therapy (TT) for PVT is an alternative to surgery and currently making a leading role. This study compares TT with tenecteplase (TNK) and streptokinase (SK) head to head in patients with mitral PVT. Methods In this single center, observational study, patients with mitral PVT diagnosed by clinical data, transthoracic echocardiography, transesophageal echocardiography, and fluoroscopy were included. After excluding patients with contraindications for thrombolysis, they were randomly assigned to receive either SK or TNK regimen. Patients were monitored for success or failure of TT and for any complications. Results Among 52 episodes (47 patients with 5 recurrences) of mechanical mitral PVT, 40 patients were thrombolyzed with SK and 12 patients were thrombolyzed with TNK. Baseline characteristics including demographic profile, clinical and echocardiographic features, and valve types were not statistically significant between the groups. Complete success rate was 77.5% in SK group and 75% in TNK group (p = 0.88). Partial success rate, failure rate, and major complications were not statistically significant between the two groups. Within 12 h of therapy, TNK showed complete success in 33.3% of patients compared to 15% in SK group (p-value <0.02). Minor bleeding was more common in TNK group. Conclusion Slow infusion of TNK is equally efficacious but more effective than SK in the management of mitral mechanical PVT. 75% to 77.5% of PVT patients completely recovered from TT and it should be the first line therapy where the immediate surgical options were remote.

Intracoronary tenecteplase in STEMI with massive thrombus

Primary percutaneous coronary intervention is the current standard of care in ST elevation myocardial infarction (STEMI). However, large thrombus is an independent predictor for stent thrombosis and major adverse cardiac events in patients undergoing primary angioplasty for STEMI. Here we report a series of STEMI patients with large thrombus burden treated successfully with low dose intracoronary thrombolysis. There was prompt and early ST resolution. There was improvement in thrombolysis in myocardial infarction (TIMI) flow and myocardial blush grade postlysis in all patients. Majority had recanalised infarct related coronary artery thus obviating the need for stenting. There was no inhospital or 1 month mortality or bleeding events. Hence intracoronary thrombolysis is an option in patients with large thrombus burden.

Penumbral Imaging-Based Thrombolysis with Tenecteplase Is Feasible up to 24 Hours after Symptom Onset / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Thrombolysis >4.5 hours after ischemic stroke onset is unproven. We assessed the feasibility of tenecteplase (TNK) treatment in patients with evidence of an ischemic penumbra 4.5 to 24 hours after onset. METHODS: Acute ischemic stroke patients underwent perfusion computed tomography (CT)/magnetic resonance imaging. Patients with cerebral blood volume (CBV) or diffusion weighted imaging Alberta Stroke Program Early CT Scores (ASPECTS) >6 and mismatch score >2 (defined as >2 ASPECTS regions with delay on mean transit time maps and normal CBV) were eligible for treatment with TNK (0.25 mg/kg). Patients with mismatch patterns enrolled in non-endovascular/non-thrombolysis trials and those without mismatch patterns served as comparators. RESULTS: The median (interquartile range) baseline National Institutes of Health Stroke Scale (NIHSS) in TNK treated patients (n=16) was 12 (range, 8 to 15). In the untreated mismatch (n=18) and nonmismatch (n=23) groups, the baseline NIHSS was 12 (range, 7 to 12) and 16 (range, 8 to 20; P=0.09) respectively. There was one symptomatic hemorrhage each in the TNK group (parenchymal hematoma [PH] 2) and non-mismatch group (PH 2). Penumbral salvage volumes were higher in TNK treated patients (48.3 mL [range, 24.9 to 80.4]) than the non-mismatch (–90.8 mL [range, –197 to –20]; P < 0.0001) patients. CONCLUSIONS: This prospective, non-randomized study supports the feasibility of TNK therapy in patients with evidence of ischemic penumbra 4 to 24 hours after onset.

Intravenous thrombolysis for acute ischemic stroke: New evidence and focus / 第二军医大学学报

Acute ischemic stroke (AIS) has the characteristics of high morbidity, disability and mortality. Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) for AIS in time window is an effective treatment recommended by domestic and overseas guidelines. However, intravenous thrombolysis has shortcomings, such as short time window, low recanalization rate and high risk of bleeding. Therefore, in recent years, studies on prolonging the time window, using low-dose rt-PA or a new generation of thrombolytic agent, and thrombolysis combined with anti-thrombotic therapy have been carried out worldwide. Based on the studies on intravenous thrombolysis, this paper discusses several issues, including extending time window, low-dose rt-PA thrombolysis, and new generation of thrombolytic agent.

Thrombolysis for stroke in a tertiary care center from Hyderabad

Background: Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) within 4.5 hours of symptom onset is currently approved for treatment of acute ischemic stroke. It improves the rate of favourable outcomes despite the risk of hemorrhagic transformation. Aim: To study the outcomes of IV thrombolysis. Materials and methods: All patients who came to the emergency with in window period with signs and symptoms suggestive of acute ischmeic stoke were included in the study. CT brain plain was done to rule out ICH. Base line glucose and BP was recorded. NIHSS was calculated. Patients whose score was between 5-25 were given IV thrombolysis with rTPA or tenecteplase. Drug was given according to availability and it was free of cost Results: Total of 41 patients was given thrombolysis. 28 were given alteplase and 13 were given tenecteplase. Improvement in NIHSS was 3.34 points at the time of discharge. Almost 40% improved significantly improved in follow up mRS scores Conclusion: Our study concluded that thrombolysis for ischemic stroke provides early functional ability and decreased morbidity without any significant risk of bleeding

Management of Acute Submacular Hemorrhage with Intravitreal Injection of Tenecteplase, Anti-vascular Endothelial Growth Factor and Gas

PURPOSE: To evaluate the visual and anatomical outcomes for neovascular age-related macular degeneration with submacular hemorrhage after intravitreal injections of tenecteplase (TNK), anti-vascular endothelial growth factor (VEGF) and expansile gas. METHODS: This study was a retrospective clinical case series following 25 eyes of 25 patients. All patients received a triple injection using 0.05 mL TNK (50 µg), 0.05 mL anti-VEGF and 0.3 mL of perfluoropropane gas. Retreatment with anti-VEGF was performed as needed. Preoperative and postoperative best-corrected visual acuity and central retinal thickness were analyzed. RESULTS: The mean logarithm of the minimum angle of resolution of best-corrected visual acuity improved significantly from 1.09 ± 0.77 at baseline to 0.52 ± 0.60 at 12 months (p < 0.001). The mean central retinal thickness also improved significantly from 545 ± 156 at baseline to 266 ± 107 at 12 months (p < 0.001). A visual improvement of 0.3 logarithm of the minimum angle of resolution unit or more was achieved in 15 eyes (60%). During the 12 postoperative months, an average of 4.04 intravitreal anti-VEGF injections was applied. CONCLUSIONS: A triple injection of TNK, anti-VEGF, and a gas appears to be safe and effective for the treatment of submacular hemorrhage secondary to neovascular age-related macular degeneration.

Treatment of ST Elevation Myocardial Infarction from Fibrinolysis to Primary PCI: In Terms of Risks and Benefits.

The treatment of ST elevation myocardial infarction (STEMI) has undergone significant advances over the past three decades. Current practice guidelines raise the importance of promptly restoring normal coronary blood flow and myocardial perfusion in the infarct zone after the onset of chest pain, through either pharmacologic or mechanical reperfusion strategies. Fibrinolytic therapy remains the most widely used reperfusion strategy worldwide. With the development of newer fibrinolytic agents and adjuvant potent anti-platelets therapies, this approach carries an increased risk of bleeding complications. The current research present up-date review of the use of reperfusion strategies for the treatment of STEMI, using data through the search of MEDLINE, PubMed, EMBASE, as well as related extracts from the annual report of the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. We summarized data from the available studies conducted over the past last 30 years in relation to pharmacologic reperfusion therapy in regards to risks and benefits. Conclusion: Fibrinolytic therapy remains the main reperfusion strategy used for the treatment of STMI worldwide. In the current era, there is a lack of fibrinolytic therapy trials, mainly because of increased focus in mechanical reperfusion therapies’ studies in the developed world. Clinical trials on the use of the fibrinolytics with newer platelet agents are urgently needed.

Efficacy and safety of single-bolus tenecteplase compared with front-loaded alteplase in Chinese patients with acute myocardial infarction / 老年心脏病学杂志（英文版）

Background and Objective Previous study showed tenecteplase and alteplaxe were equovalent for 30-day mortality in the treatment of acute myocardial infarction. The purpose of this open-label, randomized, multi-center, angiographic trial was to assess the efficacy and safety of tenecteplase compared with alteplase in Chinese patients with acute myocardial infarction. Methods We recruited patients with acute ST-elevation myocardial infarction presenting within 6 hours of symptom onset from October, 2002 to March,2004, in 5 hospitals in Beijing. After giving informed consent, patients were randomly assigned a single-bolus injection of tenecteplase (30-50 mg according to body weight) or front loaded alteplase (100 mg), and underwent coronary angiography at 90 min after starting the study drug. All patients received aspirin and heparin (target activated partial thromboplastin time 50-70 s). The primary efficacy end point was the rate of TIMI grade 3 flow at 90 minutes. Other efficacy end points included TIMI grade 2/3 flow at 90 minutes. Safety end points included all stroke, intracranial hemorrhage (ICH), moderate/severe hemorrhage (except for ICH), all-cause mortality at 30-days, and major non-fatal cardiac events at 30 days. Results Overall 110 patients were eligible for statistical analysis, with 58 patients assigned to receive tenecteplase and 52 patients to alteplase. Tenecteplase produced a rate of TIMI grade 3 flow at 90 minutes after the start of thrombolysis(68.4%) similar to that of alteplase (66.7%, P=1.0); the rates of TIMI grade 2 or 3 were similar for patients treated with tenecteplase versus alteplase (89.5% versus 80.4%, respectively, P=0.278). At 30 days, rates for all strokes were similar for the two groups (5.17% for tenecteplase and 1.92% for alteplase, P=0.62); rates of ICH were 3.45% and 1.92% (tenecteplase and rt-PA,P=1.00) respectively. The rate of moderate/severe hemorrhage was 8.62% with tenecteplase and 5.77% with alteplase (P=0.72); total mortality was almost identical in the two groups (13.8% versus 9.6%, respectively, P=0.565) while the rates of non-fatal cardiac complications were 10.35% and 11.54% (tenecteplase and alteplase, P=1.0). Conclusions The efficacy of a single-bolus, weightadjusted tenecteplase fibrinolytic regimen is equivalent to front-loaded alteplase in terms of the rates of TIMI grade 3 flow, and TIMI 2 or 3 flow, but the 30-day mortality and ICH in both groups was so high that the use of tenecteplase is not permitted in China. These negative safety results might be due to the high rate of percutaneous coronary intervention (PCI) and high dose of bolus heparin and suboptimal concomitant medical therapy during hospitalization, so further studies are needed to confirm the safety for tenecteplase in Chinese patients.