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BACKGROUND: Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non-wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups. METHODS: Patients with an unknown-onset stroke were evaluated using individual patient-level data of 2 randomized controlled trials (WAKE-UP [Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke], THAWS [Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg]) comparing IVT with placebo or standard treatment from the EOS (Evaluation of Unknown-Onset Stroke Thrombolysis trial) data set. A favorable outcome was prespecified as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. The IVT effect was compared between the treatment groups in the WUS and non-WUS with multivariable logistic regression analysis. RESULTS: Six hundred thirty-four patients from 2 trials were analyzed; 542 had WUS (191 women, 272 receiving alteplase), and 92 had non-WUS (42 women, 43 receiving alteplase). Overall, no significant interaction was noted between the mode of onset and treatment effect (P value for interaction=0.796). In patients with WUS, the frequencies of favorable outcomes were 54.8% and 45.5% in the IVT and control groups, respectively (adjusted odds ratio, 1.47 [95% CI, 1.01-2.16]). Death occurred in 4.0% and 1.9%, respectively (P=0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively (P=0.194). In patients with non-WUS, no significant difference was observed in favorable outcomes relative to the control (37.2% versus 29.2%; adjusted odds ratio, 1.76 [0.58-5.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control. CONCLUSIONS: There was no difference in the effect of IVT between patients with WUS and non-WUS. IVT showed a significant benefit in patients with WUS, while there was insufficient statistical power to detect a substantial benefit in the non-WUS subgroup. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: CRD42020166903.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Femenino , Activador de Tejido Plasminógeno , Fibrinolíticos , Terapia Trombolítica/efectos adversos , Resultado del Tratamiento , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/inducido químicamente , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Hemorragias Intracraneales/etiología , Isquemia Encefálica/tratamiento farmacológicoRESUMEN
BACKGROUND AND PURPOSE: Orolingual angioedema (OA) represents a rare but life-threatening complication among patients with acute ischemic stroke treated with intravenous thrombolysis with alteplase. Novel agents, including icatibant, are recommended in resistant patients with alteplase-induced OA who have failed to respond to first-line therapies including corticosteroids, antihistamines, and/or adrenaline. METHODS: We present a patient with alteplase-induced OA who showed substantial clinical improvement following the administration of icatibant. RESULTS: We describe a 71-year-old woman with known arterial hypertension under treatment with angiotensin-converting enzyme inhibitor, who presented with acute ischemic stroke in the territory of the right middle cerebral artery and received intravenous alteplase. During intravenous thrombolysis, the case was complicated with OA without any response to standard anaphylactic treatment including corticosteroids, dimetindene, and adrenaline. Thirty minutes after symptom onset, icatibant, a synthetic selective bradykinin B2-receptor antagonist, was administered subcutaneously. Substantial symptomatic resolution was observed only following the icatibant administration. CONCLUSIONS: This case highlights the effectiveness of icatibant in the acute management of alteplase-induced OA. In particular, icatibant administration, following first-line therapies including corticosteroids, antihistamines, and/or adrenaline, may avert tracheostomy and intubation in resistant and refractory cases with OA following intravenous thrombolysis for acute ischemic stroke.
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Angioedema , Bradiquinina/análogos & derivados , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Femenino , Humanos , Anciano , Activador de Tejido Plasminógeno/uso terapéutico , Bradiquinina/efectos adversos , Respiración Artificial , Angioedema/inducido químicamente , Angioedema/tratamiento farmacológico , Epinefrina/efectos adversos , Corticoesteroides/uso terapéutico , Antagonistas de los Receptores Histamínicos/efectos adversos , Accidente Cerebrovascular/tratamiento farmacológico , Fibrinolíticos/uso terapéuticoRESUMEN
INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Femenino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Activador de Tejido Plasminógeno/efectos adversos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Imagen de Difusión por Resonancia Magnética , Resultado del Tratamiento , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Fibrinolíticos/efectos adversos , Isquemia Encefálica/tratamiento farmacológicoRESUMEN
BACKGROUND: Tissue plasminogen activator (tPA) is recommended as the preferred thrombolytic therapy for acute myocardial infarction (AMI). This study aimed to explore tPA-related adverse events (AEs) reported in the United States Food and Drug Administration Adverse Event Reporting System (FAERS), assess the potential safety of three preferred tPA therapies for treating AMI, and provide guidance for selecting tPA for prehospital thrombolysis. METHOD: Four algorithms, including ROR, PRR, BCPNN, and MGPS, were used to quantify the signals of Tenecteplase, Reteplase, and Alteplase related AEs and compare the differential degrees of the three tPA-associated AEs in the actual data. RESULT: We detected 18 signals of Tenecteplase-induced AE, 29 signals of Reteplase-induced AE, and 22 signals of Alteplase-induced AE. Among the three drugs, Tenecteplase had the highest signal intensity for intracranial hemorrhage-related AE, followed by Alteplase. Besides, Reteplase had the highest signal intensity for procedure-related AE and Alteplase had the highest signal intensity for arrhythmia-related AE. The time-onset analysis indicates that we should be vigilant for AEs, especially within the first week and the first 1-2 days after medication. CONCLUSION: This study identified and compared the signals of AE related to Tenecteplase, Reteplase, and Alteplase in AMI patients.
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Sistemas de Registro de Reacción Adversa a Medicamentos , Bases de Datos Factuales , Fibrinolíticos , Infarto del Miocardio , Farmacovigilancia , Terapia Trombolítica , Activador de Tejido Plasminógeno , Humanos , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/diagnóstico , Fibrinolíticos/efectos adversos , Resultado del Tratamiento , Estados Unidos , Terapia Trombolítica/efectos adversos , Masculino , Factores de Riesgo , Femenino , Medición de Riesgo , Persona de Mediana Edad , Anciano , Tenecteplasa/efectos adversos , Tenecteplasa/uso terapéutico , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , United States Food and Drug AdministrationRESUMEN
High-risk pulmonary embolism (PE) is a life-threatening disease state with current guidelines recommending reperfusion therapy with systemic thrombolytics in addition to anticoagulation. This was a prospective observational cohort study with a historical control group comparing tenecteplase to alteplase for the treatment of PE or cardiac arrest with suspected PE. The primary outcome was the incidence of institutional protocol deviations defined as incorrect thrombolytic dose administered or the incorrect product compounded. Secondary outcomes included any bleeding event, major bleeding event, all-cause mortality, and for patients with a cardiac arrest, successful return of spontaneous circulation (ROSC). Fifty-four patients were included in the study. Protocol deviations occurred in one patient receiving tenecteplase and one patient receiving alteplase (4.0% vs 3.4%; P = 1.0). There was no difference in all-cause mortality (80% vs 86.2%; P = .72), any bleed (12% vs 13.8%; P = 1.0), major bleed (8.0% vs 6.9%; P = 1.0), or ROSC achievement (22.2% vs 28.6%; P = .73) when comparing tenecteplase to alteplase. Our study demonstrates that tenecteplase may be an alternative thrombolytic to alteplase for treatment of PE or cardiac arrest with suspected PE. Further studies comparing the different systemic thrombolytic agents for PE or cardiac arrest with suspected PE are needed.
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OBJECTIVE: To compare the efficacy of urokinase and alteplase intravenous thrombolysis in the treatment of acute phase cerebral infarction and investigate their impact on serum S-100ß and nerve growth factor (NGF) levels. METHODS: Parameters assessed included NIHSS score reduction, vascular recanalization rates, mRS, Barthel Index, and adverse reactions. Post-treatment blood samples were also collected for further analysis. RESULTS: The clinical treatment effectiveness and Vascular recanalization rate in Group A was higher than in Group B, with p < 0.05. After treatment, the NIHSS score in Group A was lower than in Group B (p < 0.05), and the mRS score was slightly lower, but the difference was not significant (p > 0.05). After treatment, the levels of IL-6, TNF-α, and CRP in Group A were lower than in the control group (p < 0.05). The S-100ß level in Group A was lower than in Group B, and NGF level was higher than in Group B (p < 0.05). Group A had better prognosis. CONCLUSION: The efficacy and safety of both urokinase and alteplase intravenous thrombolysis for acute phase cerebral infarction have been demonstrated, yet disparities exist in neurological function recovery and regulation of biochemical indicators. Alteplase intravenous thrombolysis emerges as the superior option, displaying greater effectiveness and safety, alongside improved regulation of serum S-100ß and NGF levels. Tailoring treatment plans to individual patient characteristics and drug mechanisms is essential. Given these findings, the promotion of alteplase intravenous thrombolysis in the management of acute phase cerebral infarction is justified.
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BACKGROUND: Pulmonary embolism (PE) leads to many emergency department visits annually. Thrombolytic agents, such as alteplase, are currently recommended for massive PE, but genetically modified tenecteplase (TNK) presents advantages. Limited comparative studies exist between TNK and alteplase in PE treatment. OBJECTIVE: The aim of this study was to assess the safety and mortality of TNK compared with alteplase in patients with PE using real-world evidence obtained from a large multicenter registry. Primary outcomes included mortality, intracranial hemorrhage, and blood transfusions. METHODS: This retrospective cohort study used the TriNetX Global Health Research Network. Patients aged 18 years or older with a PE diagnosis (International Classification of Diseases, 10th Revision, Clinical Modification code I26) were included. The following two cohorts were defined: TNK-treated (29 organizations, 266 cases) and alteplase-treated (22,864 cases). Propensity matching controlled for demographic characteristics, anticoagulant use, pre-existing conditions, and vital sign abnormalities associated with PE severity. Patients received TNK or alteplase within 7 days of diagnosis and outcomes were measured at 30 days post thrombolysis. RESULTS: Two hundred eighty-three patients in each cohort were comparable in demographic characteristics and pre-existing conditions. Mortality rates at 30 days post thrombolysis were similar between TNK and alteplase cohorts (19.4% vs 19.8%; risk ratio 0.982; 95% CI 0.704-1.371). Rates of intracerebral hemorrhages and transfusion were too infrequent to analyze. CONCLUSIONS: This study found TNK to exhibit a similar mortality rate to alteplase in the treatment of PE with hemodynamic instability. The results necessitate prospective evaluation. Given the cost-effectiveness and ease of administration of TNK, these findings contribute to the ongoing discussion about its adoption as a primary thrombolytic agent for stroke and PE.
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INTRODUCTION: Previously published data are conflicting regarding the ability of tenecteplase versus alteplase to produce early recanalization of an intracranial large vessel occlusion. We compared the performance of each thrombolytic in a stroke network. METHODS: We queried our prospectively collected code stroke registry for basilar, internal carotid, or proximal middle cerebral artery occlusion patients treated with intravenous thrombolysis from 11/17/2021-9/16/2023. The primary outcome was early recanalization, defined using angiographic or clinical criteria. Secondary and safety outcomes included 90-day functional independence and symptomatic intracranial hemorrhage. A multivariable regression analysis was performed to determine independent associations with the primary outcome. RESULTS: 233 patients, with mean age 66.9 (16.6) years and median National Institutes of Health Stroke Scale score 15 (10-21), were included. One-hundred twenty-four of 233 (53.2 %) patients were treated with alteplase while 109/233 (46.8 %) were treated with tenecteplase. Endovascular thrombectomy was performed in 82 % of subjects. Early recanalization rates were similar between the groups (alteplase 22.6 %, tenecteplase 14.7 %; p = 0.14), as were rates of 90-day independent neurological function, symptomatic intracranial hemorrhage, and mortality. Patients with an internal carotid artery occlusion or with higher presenting stroke severity were less likely to achieve early recanalization. CONCLUSIONS: Tenecteplase and alteplase have similar rates of early recanalization, 90-day functional independence, and safety outcomes in large vessel occlusion patients. Occlusion site and stroke severity predict response to thrombolysis. Future studies may investigate other factors associated with a positive response to thrombolytics as expanded treatment indications are explored.
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INTRODUCTION: Tenecteplase has been compared to alteplase in acute stroke randomized trials, with similar outcomes and safety measures, but higher doses of tenecteplase have been associated with higher hemorrhage rates in some studies. Limited data are available on the safety of tenecteplase outside of clinical trials. METHODS: We examined the safety measures of intracranial hemorrhage, angioedema, and serious extracranial adverse events in a 21-hospital integrated healthcare system that switched from alteplase (0.9 mg/kg, maximum dose 90 mg) to tenecteplase (0.25 mg/kg, maximum dose 25 mg) for acute ischemic stroke. RESULTS: Among 3,689 subjects, no significant differences were seen between tenecteplase and alteplase in the rate of intracranial hemorrhage (ICH), parenchymal hemorrhage, or volume of parenchymal hemorrhage. Symptomatic hemorrhage (sICH) was not different between the two agents: sICH by NINDS criteria was 2.0 % for alteplase vs 2.3 % for tenecteplase (P = 0.57), and sICH by SITS criteria was 0.8 % vs 1.1 % (P = 0.39). Adjusted logistic regression models also showed no differences between tenecteplase and alteplase: the odds ratio for tenecteplase (vs alteplase) modeling sICH by NINDS criteria was 0.9 (95 % CI 0.33 - 2.46, P = 0.83) and the odds ratio for tenecteplase modeling sICH by SITS criteria was 1.12 (95 % CI 0.25 - 5.07, P = 0.89). Rates of angioedema and serious extracranial adverse events were low and did not differ between tenecteplase and alteplase. Elapsed door-to-needle times showed a small improvement after the switch to tenecteplase (51.8 % treated in under 30 min with tenecteplase vs 43.5 % with alteplase, P < 0.001). CONCLUSION: In use outside of clinical trials, complication rates are similar between tenecteplase and alteplase. In the context of a stroke telemedicine program, the rates of hemorrhage observed with either agent were lower than expected based on prior trials and registry data. The more easily prepared tenecteplase was associated with a lower door-to-needle time.
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Angioedema , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Activador de Tejido Plasminógeno/efectos adversos , Tenecteplasa/efectos adversos , Fibrinolíticos/efectos adversos , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/inducido químicamente , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/inducido químicamente , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/tratamiento farmacológico , Angioedema/inducido químicamente , Resultado del Tratamiento , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/inducido químicamenteRESUMEN
OBJECTIVES: Tenecteplase (TNK) is a promising alternative to alteplase (ALT) as the thrombolytic agent for acute ischemic stroke (AIS). However, its clinical outcomes in certain populations remain unclear. This study aimed to compare the efficacy and safety among different doses of TNK in AIS patients. METHODS: We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Embase for studies comparing at least one dose of TNK to another dose of TNK or ALT 0.90 mg/kg. We conducted Bayesian network meta-analyses to estimate the relative risks (RRs) and 95% credible intervals (CrIs) for all outcomes using ALT 0.90 mg/kg as the reference. The treatments were ranked according to their surface under the cumulative ranking (SUCRA) values. RESULTS: We included 11 trials from 16 publications comprising 5423 participants. There were no significant differences between any doses of TNK and ALT for reperfusion, 3-month modified Rankin Score (mRS) 0-1 (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.68), mRS 0-2 (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.86), mortality (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.82), intracranial hemorrhage (ICH) (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.88), symptomatic ICH (sICH) (rank 1st: TNK 0.10 mg/kg; SUCRA = 0.70), and parenchymal hematoma (rank 1st: TNK 0.10 mg/kg; SUCRA = 0.68). TNK 0.40 mg/kg had a significantly higher sICH rate compared to TNK 0.25 mg/kg (RR = 2.39, 95% CrI = 1.00-7.92). Among elderly patients, TNK 0.25 mg/kg had a significantly lower rate of sICH than ALT 0.9 mg/kg (RR = 3.0 × 10-13, 95% CrI = 3.4 × 10-40-0.07). CONCLUSIONS: TNK has efficacy and safety outcomes comparable to those of ALT. TNK 0.25 mg/kg may be the optimal dose of TNK for patients with AIS.
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Fibrinolíticos , Accidente Cerebrovascular Isquémico , Metaanálisis en Red , Tenecteplasa , Humanos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/diagnóstico , Tenecteplasa/administración & dosificación , Tenecteplasa/efectos adversos , Resultado del Tratamiento , Anciano , Masculino , Femenino , Persona de Mediana Edad , Terapia Trombolítica/efectos adversos , Factores de Riesgo , Anciano de 80 o más Años , Factores de Tiempo , Recuperación de la Función , Evaluación de la Discapacidad , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/efectos adversosRESUMEN
BACKGROUND: Tenecteplase (TNK) is considered a promising option for the treatment of acute ischemic stroke (AIS) with the potential to decrease door-to-needle times (DTN). This study investigates DTN metrics and trends after transition to tenecteplase. METHODS: The Lone Star Stroke (LSS) Research Consortium TNK registry incorporated data from three Texas hospitals that transitioned to TNK. Subject data mapped to Get-With-the-Guidelines stroke variables from October 1, 2019 to March 31, 2023 were limited to patients who received either alteplase (ALT) or TNK within the 90 min DTN times. The dataset was stratified into ALT and TNK cohorts with univariate tables for each measured variable and further analyzed using descriptive statistics. Logistic regression models were constructed for both ALT and TNK to investigate trends in DTN times. RESULTS: In the overall cohort, the TNK cohort (n = 151) and ALT cohort (n = 161) exhibited comparable population demographics, differing only in a higher prevalence of White individuals in the TNK cohort. Both cohorts demonstrated similar clinical parameters, including mean NIHSS, blood glucose levels, and systolic blood pressure at admission. In the univariate analysis, no difference was observed in median DTN time within the 90 min time window compared to the ALT cohort [40 min (30-53) vs 45 min (35-55); P = .057]. In multivariable models, DTN times by thrombolytic did not significantly differ when adjusting for NIHSS, age (P = .133), or race and ethnicity (P = .092). Regression models for the overall cohort indicate no significant DTN temporal trends for TNK (P = .84) after transition; nonetheless, when stratified by hospital, a single subgroup demonstrated a significant DTN upward trend (P = 0.002). CONCLUSION: In the overall cohort, TNK and ALT exhibited comparable temporal trends and at least stable DTN times. This indicates that the shift to TNK did not have an adverse impact on the DTN stroke metrics. This seamless transition is likely attributed to the similarity of inclusion and exclusion criteria, as well as the administration processes for both medications. When stratified by hospital, the three subgroups demonstrated variable DTN time trends which highlight the potential for either fatigue or unpreparedness when switching to TNK. Because our study included a multi-ethnic cohort from multiple large Texas cities, the stable DTN times after transition to TNK is likely applicable to other healthcare systems.
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Fibrinolíticos , Accidente Cerebrovascular Isquémico , Sistema de Registros , Tenecteplasa , Terapia Trombolítica , Tiempo de Tratamiento , Humanos , Texas/epidemiología , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Masculino , Femenino , Factores de Tiempo , Anciano , Tiempo de Tratamiento/tendencias , Tenecteplasa/uso terapéutico , Tenecteplasa/administración & dosificación , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/diagnóstico , Terapia Trombolítica/tendencias , Terapia Trombolítica/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/efectos adversosRESUMEN
BACKGROUND AND PURPOSE: Post thrombolytic intracerebral hemorrhage (ICH) is associated with higher rate of death or disability in acute ischemic stroke patients. We investigated the relationship between post thrombolytic ICH volume and change in volume and death or disability at 90 days in acute ischemic stroke patients. METHODS: We analyzed 110 patents recruited in the Safety Evaluation of 3K3A-APC in Ischemic Stroke (RHAPSODY) trial who received intravenous tissue plasminogen activator (tPA) followed by mechanical thrombectomy (if indicated) and 3K3A-APC or placebo. ICH volume was measured at Day 2 and Day 7 using susceptibility weighted sequence (SWI) on magnetic resonance imaging (MRI). We also calculated the post thrombolytic ICH volume change between Day 2 and Day 7. Outcomes were determined by using utility weighted modified Rankin scale (UW-mRs) at 90-days, Outcomes were determined by using utility weighted modified Rankin scale (UW-mRS) at 90 days. To minimize interpretation bias, outcome assessors were blinded to the treatment allocation and clinical data.We adjusted for age, gender, National Institutes of Health Stroke Scale (NIHSS) score (<10,10-19 and ≥20), location of hemorrhage (single basal ganglia hemorrhage, single lobar, single cerebellum, and multiple sites) in multivariate regression analysis. RESULTS: A total of 88 (80%) of 110 patients had post thrombolytic ICH (mean volume 28.3 ml ± SD 62 ml). The strata of ICH volume were not associated with UW-mRs at 90 days: <20 cc (regression coefficient (RC)-0.05, p= 0.58), 20-39 cc (RC-0.22, p=0.17), or ≥40 cc (RC-0.34, p= 0.083) compared with no ICH after adjusting for potential confounders. Change in ICH mean volume 26.78 ml ±59.68, 52 had increase in volume) between Day 2 and day 7 was not associated with UW-mRS at 90 days (RC -67.71, p= 0.06). CONCLUSIONS: We did not observe any independent effect of post thrombolytic ICH volume on death or disability in acute ischemic stroke patients. Although further studies must be done, our data suggest that strategies to prevent ICH expansion such as antifibrinolytic medications and reduction in ICH volume such as surgical evacuation may not reduce death or disability in acute ischemic stroke patients with post thrombolytic ICH.
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BACKGROUND: Tenecteplase (TNK) is gaining recognition as a novel therapy for acute ischemic stroke (AIS). Despite TNK offering a longer half-life, time and cost saving benefits and comparable treatment and safety profiles to Alteplase (ALT), the adoption of TNK as a treatment for AIS presents challenges for hospital systems. OBJECTIVE: Identify barriers and facilitators of TNK implementation at acute care hospitals in Texas. METHODS: This prospective survey used open-ended questions and Likert statements generated from content experts and informed by qualitative research. Stroke clinicians and nurses working at 40 different hospitals in Texas were surveyed using a virtual platform. RESULTS: The 40 hospitals had a median of 34 (IQR 24.5-49) emergency department beds and 42.5 (IQR 23.5-64.5) inpatient stroke beds with 506.5 (IQR 350-797.5) annual stroke admissions. Fifty percent of the hospitals were Comprehensive Stroke Centers, and 18 (45 %) were solely using ALT for treatment of eligible AIS patients. Primary facilitators to TNK transition were team buy-in and a willingness of stroke physicians, nurses, and pharmacists to adopt TNK. Leading barriers were lack of clinical evidence supporting TNK safety profile inadequate evidence supporting TNK use and a lack of American Heart Association guidelines support for TNK administration in all AIS cases. CONCLUSION: Understanding common barriers and facilitators to TNK adoption can assist acute care hospitals deciding to implement TNK as a treatment for AIS. These findings will be used to design a TNK adoption Toolkit, utilizing implementation science techniques, to address identified obstacles and to leverage facilitators.
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Accidente Cerebrovascular Isquémico , Tenecteplasa , Humanos , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Estudios Prospectivos , Tenecteplasa/uso terapéutico , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: Data on prior use of Tenecteplase versus Alteplase in acute stroke management by mechanical thrombectomy are controversial. Our primary objective was to make a comprehensive comparative assessment of clinical and angiographic efficacy and safety outcomes in a large prospective observational study. METHODS: We included stroke patients who were eligible for intravenous thrombolysis and endovascular thrombectomy between 2019 and 2021, from an ongoing registry in twenty comprehensive stroke centers in France. We divided patients into two groups based on the thrombolytic agent used (Alteplase vs Tenecteplase). We then compared their treatment times, and their angiographic (TICI scale), clinical (mRS at three months and sICH) and safety outcomes after controlling for potential confounders using propensity score methods. RESULTS: We evaluated 1131 patients having undergone thrombectomy for the final analysis, 250 received Tenecteplase and 881 Alteplase. Both groups were of the same median age (75 vs 74 respectively), and had the same baseline NIHSS score (16) and ASPECTS (8). There was no significant difference for First Pass Effect (OR 0.93, 95 % CI 0.76-1.14, p = 0.75), time required for reperfusion (OR 0.03, 95 % CI 0.09-0.16, p = 0.49), or for final reperfusion status. Clinically, functional independence at 90 days was similar in both groups (OR 0.82, 95 % CI 0.61-1.10, p = 0.18) with the same risk of sICH (OR 1.36, 95 % CI 0.77-2.41, p = 0.28). However, Tenecteplase patients had shorter imaging-to-groin puncture times (99 vs 142 min, p < 0.05). CONCLUSIONS: Tenecteplase showed no better clinical or angiographic impact on thrombectomy compared to Alteplase. Nevertheless, it appeared associated with a shorter thrombolysis-to-groin puncture time.
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Fibrinolíticos , Sistema de Registros , Tenecteplasa , Trombectomía , Activador de Tejido Plasminógeno , Humanos , Tenecteplasa/uso terapéutico , Masculino , Femenino , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Fibrinolíticos/uso terapéutico , Trombectomía/métodos , Estudios Prospectivos , Resultado del Tratamiento , Angiografía Cerebral , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Francia , Persona de Mediana Edad , Anciano de 80 o más Años , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/cirugíaRESUMEN
OBJECTIVE: To improve the results of treatment of deep vein thrombosis of the upper extremities sing endovascular technologies. MATERIAL AND METHODS: We analyzed safety and effectiveness of treatment in 24 patients with deep vein thrombosis of the upper extremities. All ones were divided into 2 homogeneous groups by 12 people each. In the first group, conventional anticoagulation was performed. In the second group, we used additional regional catheter thrombolysis with alteplase and, if necessary, venous stenting or balloon angioplasty for residual stenosis. Patients received apixaban at baseline and throughout 6 postoperative months. After 12 months, we performed ultrasound and clinical examination to identify deep vein patency and venous outflow disorders. Vein recanalization was evaluated as follows: <50% - minimal, 50-99% - partial, 100% - complete. The quality of life of patients was studied using the SF-36 questionnaire. RESULTS: In the first group, we observed complete vein recanalization in 25% of cases, partial - in 33%, minimal - in 41% of cases; in the second group - 83.3% and 16.7% of patients, respectively. In the first group, clinical manifestations of venous outflow disorders were absent in 25% of patients, mild disorders - 25%, moderate - 8.3%, severe - 41.7% of patients. In the second group, venous outflow was not impaired in 83.7% of patients, mild violations occurred in 16.7% of patients. In the first group, physical health was equal to 44.2±1.7 scores, psychological health - 49.3±2.3 scores; in the second group - 69.3±5.7 and 71.3±5.4 scores, respectively. CONCLUSION: Endovascular treatment improved postoperative outcomes.
Asunto(s)
Trombosis de la Vena , Humanos , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/etiología , Trombosis de la Vena/terapia , Calidad de Vida , Venas , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Stents , Extremidad Superior , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
BACKGROUND: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known; however, the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase. METHODS: Patients included were from AcT, a pragmatic, registry-linked, phase 3 randomized controlled trial comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4.5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin Scale score 0 to 1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage and 90-day mortality rates. Mixed-effects logistic regression was used to assess the following: (a) the association of stroke symptom onset to needle time; (b) door (hospital arrival) to needle time with outcomes; and (c) if these associations were modified by type of thrombolytic administered (tenecteplase versus alteplase), after adjusting for age, sex, baseline stroke severity, and site of intracranial occlusion. RESULTS: Of the 1538 patients included in this analysis, 1146 (74.5%; 591 tenecteplase and 555 alteplase) presented within 3 hours versus 392 (25.5%; 196: TNK and 196 alteplase) who presented within 3 to 4.5 hours of symptom onset. Baseline patient characteristics in the 0 to 3 hours versus 3- to 4.5-hour time window were similar, except patients in the 3- to 4.5-hour window had lower median baseline National Institutes of Health Stroke Severity Scale (10 versus 7, respectively) and lower proportion of patients with large vessel occlusion on baseline CT angiography (26.9% versus 18.7%, respectively). Type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time (Pinteraction=0.161) or door-to-needle time (Pinteraction=0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase while every 10 minutes reduction in door-to-needle time was associated with a 0.2% increase in the probability of achieving 90-day modified Rankin Scale score 0 to 1, respectively. CONCLUSIONS: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes. REGISTRATION: URL: https://classic. CLINICALTRIALS: gov; Unique identifier: NCT03889249.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adolescente , Humanos , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/inducido químicamente , Fibrinolíticos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Tenecteplasa/efectos adversos , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno , Resultado del TratamientoRESUMEN
Tenecteplase is replacing alteplase as the fibrinolytic agent of choice for the acute management of ischemic stroke in many adult stroke centers due to practical and pharmacokinetic advantages in the setting of similar outcomes. Although thrombolytic use is increasing for acute childhood stroke, there is very limited experience with tenecteplase in children for any indication, and importantly, there are no data on safety, dosing, or efficacy of tenecteplase for childhood stroke. Changes in fibrinolytic capacity over childhood, pediatric pharmacological considerations such as age-specific differences in drug clearance and volume of distribution, and practical aspects of drug delivery such as availability in children's hospitals may impact decisions about transitioning from alteplase to tenecteplase for acute pediatric stroke treatment. Pediatric and adult neurologists should prepare institution-specific guidelines and organize prospective data collection.
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Isquemia Encefálica , Accidente Cerebrovascular , Adulto , Niño , Humanos , Tenecteplasa/uso terapéutico , Activador de Tejido Plasminógeno , Isquemia Encefálica/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: White matter hyperintensities of presumed vascular origin (WMH) are the most prominent imaging feature of cerebral small vessel disease (cSVD). Previous studies suggest a link between cSVD burden and intracerebral hemorrhage and worse functional outcome after thrombolysis in acute ischemic stroke. We aimed to determine the impact of WMH burden on efficacy and safety of thrombolysis in the MRI-based randomized controlled WAKE-UP trial of intravenous alteplase in unknown onset stroke. METHODS: The design of this post hoc study was an observational cohort design of a secondary analysis of a randomized trial. WMH volume was quantified on baseline fluid-attenuated inversion recovery images of patients randomized to either alteplase or placebo in the WAKE-UP trial. Excellent outcome was defined as score of 0-1 on the modified Rankin Scale after 90 days. Hemorrhagic transformation was assessed on follow-up imaging 24-36 hours after randomization. Treatment effect and safety were analyzed by fitting multivariable logistic regression models. RESULTS: Quality of scans was sufficient in 441 of 503 randomized patients to delineate WMH. Median age was 68 years, 151 patients were female, and 222 patients were assigned to receive alteplase. Median WMH volume was 11.4 mL. Independent from treatment, WMH burden was statistically significantly associated with worse functional outcome (odds ratio, 0.72 [95% CI, 0.57-0.92]), but not with higher chances of any hemorrhagic transformation (odds ratio, 0.78 [95% CI, 0.60-1.01]). There was no interaction of WMH burden and treatment group for the likelihood of excellent outcome (P=0.443) or any hemorrhagic transformation (P=0.151). In a subgroup of 166 patients with severe WMH, intravenous thrombolysis was associated with higher odds of excellent outcome (odds ratio, 2.40 [95% CI, 1.19-4.84]) with no significant increase in the rate of hemorrhagic transformation (odds ratio, 1.96 [95% CI, 0.80-4.81]). CONCLUSIONS: Although WMH burden is associated with worse functional outcome, there is no association with treatment effect or safety of intravenous thrombolysis in patients with ischemic stroke of unknown onset. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01525290.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Sustancia Blanca , Humanos , Femenino , Anciano , Masculino , Activador de Tejido Plasminógeno , Fibrinolíticos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/etiología , Terapia Trombolítica/métodos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Sustancia Blanca/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Intravenous thrombolysis (IVT) with alteplase or tenecteplase before mechanical thrombectomy is the recommended treatment for large-vessel occlusion acute ischemic stroke. There are divergent data on whether these agents differ in terms of early recanalization (ER) rates before mechanical thrombectomy, and little data on their potential differences stratified by ER predictors such as IVT to ER evaluation (IVT-to-EReval) time, occlusion site and thrombus length. METHODS: We retrospectively compared the likelihood of ER after IVT with tenecteplase or alteplase in anterior circulation large-vessel occlusion acute ischemic stroke patients from the PREDICT-RECANAL (alteplase) and Tenecteplase Treatment in Ischemic Stroke (tenecteplase) French multicenter registries. ER was defined as a modified Thrombolysis in Cerebral Infarction score 2b-3 on the first angiographic run, or noninvasive vascular imaging in patients with early neurological improvement. Analyses were based on propensity score overlap weighting (leading to exact balance in patient history, stroke characteristics, and initial management between groups) and confirmed with adjusted logistic regression (sensitivity analysis). A stratified analysis based on pre-established ER predictors (IVT-to-EReval time, occlusion site, and thrombus length) was conducted. RESULTS: Overall, 1865 patients were included. ER occurred in 156/787 (19.8%) and 199/1078 (18.5%) patients treated with tenecteplase or alteplase, respectively (odds ratio, 1.09 [95% CI, 0.83-1.44]; P=0.52). A differential effect of tenecteplase versus alteplase on the probability of ER according to thrombus length was observed (Pinteraction=0.003), with tenecteplase being associated with higher odds of ER in thrombi >10 mm (odds ratio, 2.43 [95% CI, 1.02-5.81]; P=0.04). There was no differential effect of tenecteplase versus alteplase on the likelihood of ER according to the IVT-to-EReval time (Pinteraction=0.40) or occlusion site (Pinteraction=0.80). CONCLUSIONS: Both thrombolytics achieved ER in one-fifth of patients with large-vessel occlusion acute ischemic stroke without significant interaction with IVT-to-EReval time and occlusion site. Compared with alteplase, tenecteplase was associated with a 2-fold higher likelihood of ER in larger thrombi.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Trombosis , Humanos , Activador de Tejido Plasminógeno/uso terapéutico , Tenecteplasa/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Estudios Retrospectivos , Trombectomía/métodos , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/inducido químicamente , Trombosis/tratamiento farmacológico , Resultado del Tratamiento , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/inducido químicamenteRESUMEN
INTRODUCTION: The Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) showed that a low-dose alteplase was safe but not clearly non-inferior to standard-dose alteplase in acute ischemic stroke (AIS). Given the significant cost of this medicine, we undertook a cost-effectiveness analysis to determine the probability that low-dose is cost-effective relative to standard-dose alteplase in China. METHODS: For ENCHANTED participants in China with available health cost data, cost-effectiveness and cost-utility analyses were undertaken in which death or disability (modified Rankin scale scores 2-6) at 90 days and quality-adjusted life-years (QALYs) were used as outcome measures, respectively. There was adherence to standard guidelines for health economic evaluations alongside non-inferiority trials and according to a health-care payer's perspective. The equivalence margin for cost and effectiveness was set at USD 691 and -0.025 QALYs, respectively, for the base-case analysis. Probabilistic sensitivity analyses were used to evaluate the probability of low-dose alteplase being non-inferior. RESULTS: While the mean cost of alteplase was lower in the low-dose group (USD 1,569 vs. USD 2,154 in the standard-dose group), the total cost was USD 56 (95% confidence interval [CI]: -1,000-1,113) higher compared to the standard-dose group due to higher hospitalization costs in the low-dose group. There were 462 (95% CI: 415-509) and 410 (95% CI: 363-457) patients with death or disability per 1,000 patients in the low-dose and standard-dose groups, respectively. The low-dose group had marginally lower (0.008, 95% CI: -0.016-0.001) QALYs compared to their standard-dose counterparts. The low-dose group was found to have an 88% probability of being non-inferior based on cost-effectiveness versus the standard-dose group. CONCLUSIONS: This health economic evaluation alongside the ENCHANTED indicates that the use of low-dose alteplase does not save overall healthcare costs nor lead to a gain in QALYs in the management of Chinese patients with AIS compared to the use of standard dose. There is little justification on economic grounds to shift from standard-of-care thrombolysis in AIS.