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.

Comparación entre tenecteplase y alteplase en la trombolisis intravenosa del ataque cerebrovascular isquémico / Comparison between tenecteplase and alteplase in intravenous thrombolysis for acute ischemic stroke / Comparação entre tenecteplase e alteplase na trombólise intravenosa do acidente vascular cerebral 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.

Femoral Access-Site Complications with Tenecteplase versus Alteplase before Mechanical Thrombectomy for Large-Vessel-Occlusion Stroke.

BACKGROUND AND PURPOSE: IV thrombolysis with alteplase before mechanical thrombectomy for emergent large-vessel-occlusion stroke is associated with access-site bleeding complications. However, the incidence of femoral access-site complications with tenecteplase before mechanical thrombectomy requires exploration. Here, femoral access-site complications with tenecteplase versus alteplase before mechanical thrombectomy for large-vessel-occlusion stroke were compared. MATERIALS AND METHODS: All patients receiving IV thrombolytics before mechanical thrombectomy for large-vessel-occlusion stroke who presented from January 2020 to August 2022 were reviewed. In May 2021, our health care system switched from alteplase to tenecteplase as the primary thrombolytic for all patients with stroke, facilitating the comparison of alteplase-versus-tenecteplase femoral access-site complication rates. Major (requiring surgery) and minor (managed conservatively) access-site complications were assessed. RESULTS: One hundred thirty-nine patients underwent transfemoral mechanical thrombectomy for large-vessel-occlusion stroke, of whom 46/139 (33.1%) received tenecteplase and 93/139 (66.9%) received alteplase. In all cases (n = 139), an 8F sheath was inserted without sonographic guidance, and vascular closure was obtained with an Angio-Seal. Baseline demographics, concomitant antithrombotic medications, and periprocedural coagulation lab findings were similar between groups. The incidence of conservatively managed groin hematomas (2.2% versus 4.3%), delayed access-site oozing requiring manual compression (6.5% versus 2.2%), and arterial occlusion requiring surgery (2.2% versus 1.1%) was similar between the tenecteplase and alteplase groups, respectively (P = not significant). No dissection, arteriovenous fistula, or retroperitoneal hematoma was observed. CONCLUSIONS: Tenecteplase compared with alteplase before mechanical thrombectomy for large-vessel-occlusion stroke is not associated with an alteration in femoral access-site complication rates.

Outcomes with IV tenecteplase and IV alteplase for acute ischemic stroke with or without thrombectomy in real-world settings in the United States.

BACKGROUND AND PURPOSE: Although many stroke centers in United States are using intravenous (IV) tenecteplase (TNK) for acute ischemic stroke patients, there is paucity of comparative data between IV TNK and IV alteplase from real-world settings. MATERIALS AND METHODS: We analyzed the data from 122 healthcare facilities in Cerner Real World Data and included patients admitted between February 2016 to April 2022 to determine the effect of IV TNK (compared with IV alteplase) on occurrence of two outcomes in acute ischemic stroke patients stratified by use of thrombectomy: non-routine discharge or death, and intracranial hemorrhage after adjusting for potential confounders. RESULTS: Among 30,643 acute ischemic stroke patients analyzed, 29,480 (96.2%) and 1,163 (3.8%) patients received IV alteplase and IV TNK, respectively. The proportion of patients who received thrombectomy was significantly higher among patients who received IV TNK compared with those who received IV alteplase (16.7% versus 11.0%, p<0.001). Occurrence of intracranial hemorrhage was more common among patients treated with IV TNK in acute ischemic stroke patients who did not receive thrombectomy (7.9% versus 5.1%, p<0.001) but not in those who received thrombectomy (20.1% versus 16.8%, p = 0.234). In the logistic regression analysis, patients treated with IV TNK who did not receive thrombectomy were at higher risk of intracranial hemorrhage (OR, 1.34, 95% CI 1.05-1.72, p = 0.02) after adjusting for age (age strata), gender, race/ethnicity, hypertension, diabetes mellitus, atrial fibrillation, hyperlipidemia, malignancy, nicotine dependence, previous ischemic stroke, previous transient ischemic attack, previous intracerebral hemorrhage, previous subarachnoid hemorrhage, previous acute myocardial infarction, atherosclerosis of aorta, previous AKI, congestive heart failure, peripheral vascular disease, and hospital type, aphasia, hemiplegia, neglect, somnolence, stupor and coma, dysphagia, and homonymous hemianopsia. There was no difference in the rate of non-routine discharge or death between patients treated with IV TNK and those treated with IV alteplase in the multivariate analyses. CONCLUSIONS: In an analysis of real-world data, IV TNK was associated with higher rates of intracranial hemorrhage compared with IV alteplase in patients with acute ischemic stroke who did not undergo thrombectomy.

Tenecteplase versus alteplase before mechanical thrombectomy: experience from a US healthcare system undergoing a system-wide transition of primary thrombolytic.

BACKGROUND: Tenecteplase (TNK) is a genetically modified variant of alteplase (TPA) and has been established as a non-inferior alternative to TPA in acute ischemic stroke (AIS). Whether TNK exerts distinct benefits in large vessel occlusion (LVO) AIS is still being investigated. OBJECTIVE: To describe our first-year experience after a healthcare system-wide transition from TPA to TNK as the primary thrombolytic. METHODS: Patients with AIS who received intravenous thrombolytics between January 2020 and August 2022 were retrospectively reviewed. All patients with LVO considered for mechanical thrombectomy (MT) were included in this analysis. Spontaneous recanalization (SR) after TNK/TPA was a composite variable of reperfusion >50% of the target vessel territory on cerebral angiography or rapid, significant neurological recovery averting MT. Propensity score matching (PSM) was performed to compare SR rates between TNK and TPA. RESULTS: A total of 148 patients were identified; 51/148 (34.5%) received TNK and 97/148 (65.5%) TPA. The middle cerebral arteries M1 (60.8%) and M2 (29.7%) were the most frequent occlusion sites. Baseline demographics were comparable between TNK and TPA groups. Spontaneous recanalization was significantly more frequently observed in the TNK than in the TPA groups (unmatched: 23.5% vs 10.3%, P=0.032). PSM substantiated the observed SR rates (20% vs 10%). Symptomatic intracranial hemorrhage, 90-day mortality, and functional outcomes were similar. CONCLUSIONS: The preliminary experience from a real-world setting demonstrates the effectiveness and safety of TNK before MT. The higher spontaneous recanalization rates with TNK are striking. Additional studies are required to investigate whether TNK is superior to TPA in LVO AIS.

Comparison of tenecteplase versus alteplase in STEMI patients treated with ticagrelor: A cross-sectional study.

BACKGROUND: The effectiveness and safety of administration of ticagrelor simultaneously with fibrinolytic agents in STEMI patients remain unclear. OBJECTIVE: This study aimed to investigate the effectiveness and safety of tenecteplase against alteplase in patients with STEMI receiving a loading dose of ticagrelor. METHODS: We conducted a cross-sectional study in patients with STEMI who were reperfused with fibrinolytic. The study included 150 patients (ages 18 to 75 years) administered tenecteplase or alteplase and concomitantly given ticagrelor [180 mg loading dose, 90 mg bid (bis in die)]. Patients who had active major bleeding, died, and who were decided to have a CABG surgery as a result of coronary angiography were excluded. Patients who underwent facilitated-PCI with fibrinolysis continued to receive ticagrelor without switching to clopidogrel. The MACE (in-hospital death, TIMI flow grade, major bleeding) rates of the two groups were compared. RESULTS: The study consisted of 150 patients, comprising 99 (66%) men and 51 women (34%) with a mean age of 60,33 ± 13,83 years. Patients were divided into two groups according to the thrombolytic therapy: alteplase (n = 60) and tenecteplase (n = 90). The major adverse cardiac events (MACE) (45% vs 22.2%), bleeding (11.7% vs 2.2%), hypertension (51.7% vs 30%), atrial fibrillation (26.7% vs 12.2%), left ventricular hypertrophy (26.7% vs 10%), CRP (p < 0.001) were significantly higher and the recanalization (66.7% vs 85.4%), hematocrit (p = 0.03) were significantly lower in the alteplase group compared to the tenecteplase group. No significant differences were found between the two groups about in-hospital mortality (p = 0.151). Kaplan Meier analysis was performed in terms of MACE (TIMI flow grade 1, major bleeding, in-hospital mortality) rates during the follow-up period (Log-rank test, p = 0.032). Patients who received tenecteplase treatment had a lower MACE, according to a Kaplan-Meier analysis. CONCLUSIONS: The administration of tenecteplase in STEMI patients who received a loading dose with ticagrelor resulted in a significant reduction in MACE compared to alteplase. Larger multi-center studies are warranted to investigate the effect of tenecteplase treatment on clinical results.

Impact of poly-arginine peptides R18D and R18 on alteplase and tenecteplase thrombolysis in vitro, and neuroprotective stability to proteolysis.

The poly-arginine peptides R18D and R18 represent novel potential neuroprotective treatments for acute ischaemic stroke. Here we examined whether R18D and R18 had any significant effects on the thrombolytic activity of alteplase (tPA) and tenecteplase (TNK) on clots formed from whole blood in an in vitro thrombolysis plate assay. R18D and R18 were examined at concentrations of 0.25, 0.5, 1, 2, 4, 8 and 16 µM during the 1-h thrombolytic assay. We also included the well-characterised neuroprotective NA-1 peptide as a control. R18D, R18 and NA-1 all reduced tPA or TNK percentage clot lysis by 0-9.35%, 0-3.44% and 0-4.8%, respectively. R18D, R18 and NA-1 had a modest and variable effect on the lag time, increasing the time to the commencement of thrombolysis by 0-9.9 min, 0-5.53 min and 0-7.16 min, respectively. Lastly, R18 and NA-1 appeared to increase the maximal activity of the thrombolysis reaction. In addition, the in vitro anti-excitotoxic neuroprotective efficacy of R18D and R18 was not affected by pre-incubation for 1-2 h or overnight with tPA or TNK, whereas only R18D retained high anti-excitotoxic neuroprotective efficacy when pre-incubated in a synthetic trypsin (TrypLE Express). The present in vitro findings suggest that neither R18D or R18 when co-administered with the thrombolytic inducing agents tPA or TNK are likely to have a significant impact when used clinically during clot thrombolysis and confirm the superior proteolytic stability of the R18D peptide.

Clinical outcomes of patients with mitral prosthetic valve obstructive thrombosis treated with streptokinase or tenecteplase.

Agent of choice for thrombolytic therapy (TT) in prosthetic valve thrombosis (PVT) is unknown. 84 mitral obstructive-PVT episodes treated with TT (43: Tenecteplase; 41: Streptokinase) were included in this prospective study. The incidence of primary end-point (CCS: complete clinical success, defined as complete or partial hemodynamic success with no complications or surgery) was 84.5% with recurrent PVT as a sole predictor. Bleeding and embolic manifestations were noted in 8.3% and 4.7% of episodes respectively. Tenecteplase use was associated with lower complication rate and a mitral EOA of <0.74 cm2 at presentation predicts the need for extended thrombolysis (accuracy, 78.6%).

Systematic Analysis of Combined Thrombolysis Using Ultrasound and Different Fibrinolytic Drugs in an in Vitro Clot Model of Intracerebral Hemorrhage.

Adequate removal of blood clots by minimally invasive surgery seems to correlate with a better clinical outcome in patients with intracerebral hemorrhages (ICHs). Moreover, neurotoxic effects of recombinant tissue plasminogen activator have been reported. The aim of this study was to improve fibrinolysis using an intra-clot ultrasound application with tenecteplase and urokinase in our established ICH clot model. One hundred thirty clots were produced from 25 or 50 mL of human blood, incubated for different periods and equipped with drainage, through which an ultrasound catheter was placed in 65 treatment clots for 1 h, randomly allocated into three groups: administration of ultrasound, administration of 60 IU of tenecteplase or administration of 30,000 IU urokinase. Relative end weights were compared. This study found a significant increase in thrombolysis caused by a combination of ultrasound and fibrinolytic drugs, whereas ultrasound and tenecteplase are significantly more effective in the treatment of larger and aged clots.

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.

Manejo del síndrome coronario agudo durante pandemia por COVID ­ 19 / Management of acute coronary syndrome during COVID ­ 19 pandemic

INTRODUCTION: Acute Myocardial Infarction is a medical emergency, being his early and adequate treatment highly effective mainly in relation to reperfusion therapy. Unfortunately, COVID ­ 19 pandemic, has brought changes in its management due to availability of conditioned hemodynamic rooms, infection risk of the professionals, patient conditions and availability of critical unit beds. A review of the topic was made aimed to give a guide for the management of these patients with the available tools. MATERIALS AND METHOD: A review of the topic was made using the Medline/ Pubmed platform, in English and Spanish. Further, published articles in journals as The journal of the American college of cardiology and Circulation were included. CONCLUSIONS: The reperfusion strategies must be used according to the clinical context of the patient. In the acute myocardial infarction with ST elevation, fibrinolytic treatment may be chosen in low risk and without hemodynamic instability. In patients with hemodynamic instability, not eligible for fibrinolytic treatment or in whom this therapy fails, percutaneous angioplasty is indicated considering the protection of personnel. In the case of acute myocardial infarction without ST elevation, the treatment by urgent percutaneous angioplasty is considered in cases of hemodynamic instability or malignant arrhythmias.

Stabilizing osmolytes' effects on the structure, stability and function of tc-tenecteplase: A one peptide bond digested form of tenecteplase.

Organic osmolytes, as major cellular compounds, cause protein stabilization in the native form. In the present study, the possible chaperone effects of the three naturally occurring osmolytes on the two-chain form of tenecteplase (tc-TNK), a recombinant, genetically engineered mutant tissue plasminogen activator, have been explored by using circular dichroism, steady-state fluorescence, UV-Visible spectroscopy, and in silico experiments. The tc-TNK is derived from the one-chain protein upon disruption of one peptide bond. Thermal denaturation experiments showed a slightly more stabilizing effect of the three co-solvents on the single-chain TNK (sc-TNK) in comparison to that on tc-TNK. Unlike single-chain tenecteplase, the two-chain form undergoes reversible denaturation which is somehow perturbed in some cases as the result of the presence of osmolytes. Very minor changes in the secondary structure and the tertiary structure were observed. The molecular dynamics simulations and comparative structural analysis of catalytic domain of the protein in the single-chain and two-chain forms in pure water, mannitol/water, trehalose/water, and sucrose/water showed that while the stabilizing effect of the three osmolytes on tc-TNK might be induced by preferential accumulation of these molecules around the nonpolar and aromatic residues, that is to say, fewer water-hydrophobic residues' interactions in tc-TNK, sc-TNK is stabilized by preferential exclusion effect.

Regional QT Interval Dispersion as an Early Predictor of Reperfusion in Patients with Acute Myocardial Infarction after Fibrinolytic Therapy / A Dispersão do Intervalo QT Regional como Preditor Precoce de Reperfusão em Pacientes com Infarto Agudo do Miocárdio Pós-terapia Fibrinolítica

Abstract Background: Patients with ST-elevation acute myocardial infarction attending primary care centers, treated with pharmaco-invasive strategy, are submitted to coronary angiography within 2-24 hours of fibrinolytic treatment. In this context, the knowledge about biomarkers of reperfusion, such as 50% ST-segment resolution is crucial. Objective: To evaluate the performance of QT interval dispersion in addition to other classical criteria, as an early marker of reperfusion after thrombolytic therapy. Methods: Observational study including 104 patients treated with tenecteplase (TNK), referred for a tertiary hospital. Electrocardiographic analysis consisted of measurements of the QT interval and QT dispersion in the 12 leads or in the ST-segment elevation area prior to and 60 minutes after TNK administration. All patients underwent angiography, with determination of TIMI flow and Blush grade in the culprit artery. P-values < 0.05 were considered statistically significant. Results: We found an increase in regional dispersion of the QT interval, corrected for heart rate (regional QTcD) 60 minutes after thrombolysis (p = 0.06) in anterior wall infarction in patients with TIMI flow 3 and Blush grade 3 [T3B3(+)]. When regional QTcD was added to the electrocardiographic criteria for reperfusion (i.e., > 50% ST-segment resolution), the area under the curve increased to 0.87 [(0.78-0.96). 95% IC. p < 0.001] in patients with coronary flow of T3B3(+). In patients with ST-segment resolution >50% and regional QTcD > 13 ms, we found a 93% sensitivity and 71% specificity for reperfusion in T3B3(+), and 6% of patients with successful reperfusion were reclassified. Conclusion: Our data suggest that regional QTcD is a promising non-invasive instrument for detection of reperfusion in the culprit artery 60 minutes after thrombolysis.

Resumo Fundamento: Pacientes com infarto do miocárdico com elevação do segmento-ST atendidos em centros de atendimento primário e tratados de acordo com a estratégia fármaco-invasiva são submetidos à fibrinólise seguida de coronariografia em período de 2-24h. Neste cenário, o conhecimento de marcadores de reperfusão como a redução em 50% do segmento-ST é fundamental. Objetivo: Analisar o desempenho da dispersão do intervalo QT em adição aos critérios clássicos, como marcador precoce de reperfusão pós-terapia trombolítica. Métodos: Estudo observacional com a inclusão de 104 pacientes tratados com tenecteplase (TNKase) e referenciados a hospital de atendimento terciário. A análise dos eletrocardiogramas (ECG) consistiu em mensuração do intervalo QT e sua dispersão nas 12 derivações, e também apenas na região com supradesnivelamento-ST antes e 60min pós-TNKase. A angiografia foi realizada em todos os pacientes com obtenção do fluxo TIMI e Blush da artéria culpada. Foram considerados significantes valores de p < 0,05. Resultados: Observamos aumento da dispersão do intervalo QT, corrigido pela frequência cardíaca, regional (dQTcR) 60min pós-lise (p = 0,006) em infartos de parede anterior nos casos com fluxo TIMI 3 e Blush 3 [T3B3(+)]. Adicionando a dQTcR ao critério ECG (redução do ST > 50%) de reperfusão, a área sob a curva aumentou para 0,87 [(0,78-0,96), IC95%, p < 0,001] em pacientes com fluxo coronário T3B3(+). Nos pacientes com critério de ECG para reperfusão e dQTcR > 13 ms a sensibilidade e especificidade foram 93% e 71%, respectivamente, para reperfusão em T3B3(+), possibilitando reclassificar 6% dos pacientes com sucesso de reperfusão. Conclusão: Os dados sugerem a dQTcR como instrumento promissor na identificação não invasiva de reperfusão na artéria coronária culpada, 60min pós-trombólise.

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 12h 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.

Treatment of Prosthetic Valve Thrombosis with Bolus Dose Tenecteplase: An Experience from a Developing Country.

BACKGROUND AND AIM OF THE STUDY: Prosthetic valve thrombosis (PVT) in metallic prosthetic cardiac valves is not an uncommon condition, and has high mortality and morbidity. Although surgery is the traditional choice for PVT therapy, thrombolysis with newer agents has achieved good success rates. Many studies described in the western literature have used tissue plasminogen activators, while studies from developing countries have been largely based on the use of streptokinase and urokinase. Data regarding the use of newer agents such as tenecteplase are scant. Hence, the study aim was to evaluate the safety and efficacy of tenecteplase in left-sided PVT. METHODS AND RESULTS: Between 2013 and 2016, a total of 18 patients with PVT was treated with a 40 mg bolus dose of tenecteplase. Significantly, one patient was a pregnant lady in whom a lower dose (25 mg) was successfully and safely used. Thrombolysis was followed by enoxaparin and oral anticoagulation in patients, all of whom had complete lysis of thrombus and clinical improvement. CONCLUSIONS: Tenecteplase is an effective and excellent therapeutic agent for PVT, with a good safety margin. Its safe use in pregnancy points to a possible optional therapy, but this requires confirmation.

Thrombolysis: A Useful Tool in the Primary PCI Cupboard.

A 44-year-old woman presented to the emergency department with central crushing chest pain and dynamic anterior ST elevation on a background of a known left bundle-branch block on her electrocardiogram. Past medical history included insulin-dependent diabetes, asthma, fibromyalgia, and a gradually failing kidney transplant. This case demonstrates the rarely utilized niche role for intracoronary thrombolysis in STEMI treatment in the modern angioplasty era.

The Impact of CT Perfusion Threshold on Predicted Viable and Nonviable Tissue Volumes in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Perfusion imaging is used for patient selection in clinical practice and trials. Postprocessing and definitions of tissue viability are nevertheless not standardized. We compared the lesion volumes generated with two well-recognized perfusion tissue definitions in a single-center phase 2 thrombolysis study. METHODS: We analyzed perfusion imaging data from the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study using two popular tissue viability thresholds (ischemic core definition: (1) cerebral blood volume < 2.0 mL/100 g-1 or (2) relative cerebral blood flow < 40% that of the contralesional hemisphere and relative delay time >2 seconds; penumbra definitions: (1) mean transit time > 145% of contralesional hemisphere or (2) relative delay time < 2 seconds). We compared volumes of core and penumbra, mismatch ratio, percentage, and volume of penumbra salvaged at 24 hours. RESULTS: We included 73 (tenecteplase = 36, alteplase = 37) patients who had analyzable perfusion lesions at baseline. Significant differences were found in core volumes using the two thresholds (33 ± 37 mL vs. 26 ± 32 mL, P < .001), as was mismatch ratio (2.5 ± .9 vs. 4.2 ± 3.7, P < 0.001). The volume of penumbra salvaged at 24 hours (30 ± 19 mL vs. 35 ± 26 mL, P = .043) differed significantly, although the percentages of penumbra salvaged did not (P = .2). No difference was found between the two thrombolytic agents in the percentages of penumbra salvaged using either threshold. CONCLUSION: Two commonly used tissue definitions generated significantly different lesion volumes and mismatch ratios. Threshold selection may have significant impact on patient selection for trials or reperfusion therapies.

Microbubble-Based Sonothrombolysis Using a Planar Rectangular Ultrasonic Transducer.

BACKGROUND: The aim of the proposed study was to evaluate in an in vitro flow model the ability of small planar rectangular (2 × 10 mm2) ultrasonic transducer to enhance thrombolysis induced by the thrombolytic agent tenecteplase (TNK-tPA). METHODS: To provide a more realistic clinical environment of stroke, the study was conducted under realistic flow conditions and TNK-tPA concentrations. Fully retracted porcine blood clots were used to determine the thrombolytic efficacy of ultrasound (US) waves as an adjunct to TNK-tPA or in combination with microbubbles (MBs). Two ultrasonic flat rectangular transducers were used in the experiments, operating at 3.7 and 5.2 MHz respectively. A pulsed US protocol that maintained temperature elevation at the target of 1°C was applied. Thrombolysis efficacy was measured in milligrams of mass clot removed. RESULTS: The effect of experimental parameters, such as power, frequency, and MBs administration, on thrombolysis efficacy was explored. CONCLUSIONS: The results revealed that thrombolysis efficacy decreases at higher frequency, and therefore, the possibility of using lower frequency to improve efficacy should be further investigated. Additionally, study findings demonstrated that the combination of 3.7 MHz with MBs as an adjunct to TNK-tPA strongly enhanced thrombolysis efficacy, because with 30 minutes of treatment, 700 mg of clot was removed through nonthermal mechanisms. As a final point, this study has shown that MBs dose influences thrombolysis enhancement, because higher thrombolytic efficacy was observed with higher doses of MBs.