Alteplase For Acute Ischemic Stroke Research Articles

Contemporary Prestroke Dual Antiplatelet Use and Symptomatic Intracerebral Hemorrhage Risk After Thrombolysis

Intravenous alteplase (IV-tPA) can be administered to patients with acute ischemic stroke but is associated with symptomatic intracerebral hemorrhage (sICH). It is unclear if patients taking prestroke dual antiplatelet therapy (DAPT) are at higher risk of sICH. To determine the associated risk of sICH in patients taking prestroke dual antiplatelet therapy receiving alteplase for acute ischemic stroke using propensity score matching analysis. This cohort study used data from the American Heart Association and American Stroke Association Get With The Guidelines-Stroke (GWTG-Stroke) registry between 2013 and 2021. Data were obtained from hospitals in the GWTG-Stroke registry. This study included patients hospitalized with acute ischemic stroke and treated with IV-tPA. Data were analyzed from January 2013 to December 2021. Prestroke DAPT before treatment with IV-tPA for acute ischemic stroke. sICH, In-hospital death, discharge modified Rankin scale score, and other life-threatening systemic hemorrhages. Of 409 673 participants, 321 819 patients (mean [SD] age, 68.6 [15.1] years; 164 587 female [51.1%]) who were hospitalized with acute ischemic stroke and treated with IV-tPA were included in the analysis. The rate of sICH was 2.9% (5200 of 182 344), 3.8% (4457 of 117 670), and 4.1% (893 of 21 805) among patients treated with no antiplatelet therapy, single antiplatelet therapy (SAPT), and DAPT, respectively (P < .001). In adjusted analyses after propensity score subclassification, both SAPT (odds ratio [OR], 1.13; 95% CI, 1.07-1.19) and DAPT (OR, 1.28; 95% CI, 1.14-1.42) were associated with increased risks of sICH. Prestroke antiplatelet medications were associated with lower odds of discharge mRS score of 2 or less compared with no medication (SAPT OR, 0.92; 95% CI, 0.90-0.95; DAPT OR, 0.94; 95% CI, 0.88-0.98). Results of a subgroup analysis of patients taking DAPT exposed to aspirin-clopidogrel vs aspirin-ticagrelor combination therapy were not significant (OR, 1.35; 95% CI, 0.84-1.86). Prestroke DAPT was associated with a significantly elevated risk of sICH among patients with ischemic stroke who were treated with thrombolysis; however, the absolute increase in risk was small. Patients exposed to antiplatelet medications did not have excess sICH compared with landmark trials, which demonstrated overall clinical benefit of thrombolysis therapy for acute ischemic stroke.

AcT: Intravenous Tenecteplase Compared to Alteplase for Acute Ischaemic Stroke in Canada

AcT: Intravenous Tenecteplase Compared to Alteplase for Acute Ischaemic Stroke in Canada In this article, we detail the trial’s design and important clinical findings.

Analysis of Safety and Efficacy of the Early Initiation of Antithrombotic Secondary Prevention in Patients Treated with Intravenous Thrombolysis for Acute Ischemic Stroke.

Background and Objectives: Current guidelines and the alteplase product insert recommend that antithrombotic therapy be avoided within 24 h of intravenous thrombolytic therapy with rt-PA in acute ischemic stroke. Therefore, the rate of stroke recurrence is unclear in terms of early neurological deterioration, which we could prevent with the early administration of antithrombotic therapy. We do not know the effect of early antithrombotic therapy after intravenous thrombolysis with rt-PA in acute stroke on the outcome in patients after 90 days either. Design: Prospective monocentric observational cohort study. Methods: Data were collected from consecutive patients treated with alteplase for acute ischemic stroke between January 2015 and January 2023. We examined functional outcome at 90 days, including the risk of symptomatic intracranial hemorrhage and mortality rate as safety indicators and stroke recurrence events in both early and standard antithrombotic therapy at 24 h after intravenous thrombolysis. Results: A total of 489 patients were included, of which 278 (56.9%) were men. Of these, 407 (83.2%) patients received early antithrombotic therapy. No symptomatic intracranial hemorrhage occurred in any participants. There was a significantly higher number of patients with an excellent outcome (mRS 0-1) in early antithrombotic treatment (211 (53.1%) versus 28 (34.6%) in standard antithrombotic treatment (p = 0.002, OR 0.47, 95% CI: 0.28-0.76). Conclusions: Early antithrombotic treatment after intravenous therapy in patients with acute ischemic stroke revealed no safety concerns compared with standard antithrombotic therapy and resulted in a significantly higher proportion of patients with an excellent functional outcome.

Comparative Analysis of Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Multicentric Observational Study from Eastern India.

Tenecteplase is used as an alternative to alteplase and is considered noninferior for thrombolysis in acute ischemic stroke. To compare the effectiveness and adverse effects of tenecteplase and alteplase in the real-world management of acute ischemic stroke. In this retrospective observational study, we collected data from acute ischemic stroke patients admitted in six hospitals in West Bengal, India, and were thrombolysed with tenecteplase or alteplase between July 2021 and June 2022. Demographic data, baseline parameters, hospital course, and 3-month follow-up data were collected. The percentage of patients achieving a score of 0-2 in the modified Ranking scale at 3 months, rate of symptomatic intracranial hemorrhage, and all-cause mortality within 3 months were the main parameters of comparison between the two thrombolytic agents. A total of 162 patients were initially included in this study. Eight patients were excluded due to unavailability of follow-up data. Among the remaining patients, 71 patients received tenecteplase and 83 patients received alteplase. There was no statistically significant difference between tenecteplase and alteplase with respect to the percentage of patients achieving functional independence (modified Rankin scale score 0-2) at 3 months (53.5% vs. 60.2%, P = 0.706), rate of symptomatic intracranial hemorrhage (5.6% vs. 10.8%, P = 0.246), and all-cause mortality at 3 months (11.3% vs. 15.7%, P = 0.628). The effectiveness of tenecteplase is comparable to alteplase in the real-world management of acute ischemic stroke. Symptomatic intracranial hemorrhage and all-cause mortality rates are also similar in real-world practice.

A Systematic Review of the Efficacy and Safety of Tenecteplase Versus Alteplase in Acute Ischemic Stroke: A Time to Pass the Torch

Alteplase, a biosynthetic form of human tissue‐type plasminogen activator, is Food and Drug Administration‐approved for the treatment of acute ischemic stroke and currently the standard of care for thrombolytic therapy. Tenecteplase, a modified form of alteplase using recombinant technology, has several pharmacological advantages over alteplase, including longer half‐life, higher fibrin specificity, and greater resistance to plasminogen activator inhibitor‐1. Additionally, tenecteplase is given as a single bolus administration compared to the bolus plus 1‐hour continuous infusion of alteplase. Given these pharmacologic and logistical differences along with studies demonstrating noninferiority compared with alteplase, tenecteplase has become an alternative thrombolytic for the management of acute ischemic stroke. There is a growing body of evidence that suggests tenecteplase is a safe and effective alternative to alteplase. This systematic review evaluates the available literature for the use of tenecteplase in acute ischemic stroke and provides relevant discussion regarding role in therapy, therapeutic strategies, and areas requiring further research.

Effectiveness of Tenecteplase Versus Alteplase in Acute Ischemic Stroke Selected Subgroups of a Real-world Data Set (P2-5.005)

Effectiveness of Tenecteplase Versus Alteplase in Acute Ischemic Stroke Selected Subgroups of a Real-world Data Set (P2-5.005)

Tenecteplase versus alteplase for acute ischemic stroke: a systematic review and meta-analysis of randomized and non-randomized studies.

Alteplase is the current standard of care for acute ischemic stroke. Tenecteplase is a newer fibrinolytic agent with preferable administration and lower costs; however, its comparative effectiveness to alteplase remains uncertain. We set out to perform a systematic review and meta-analysis to establish the benefits and harms of tenecteplase versus alteplase for acute ischemic stroke. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to April 2023 for randomized and non-randomized studies that compared tenecteplase versus alteplase for acute ischemic stroke. Paired reviewers independently assessed risk of bias and extracted data. We performed both conventional meta-analyses and Bayesian network meta-analyses (NMA) with random-effects models and used the GRADE approach to evaluate the certainty of evidence. Our primary efficacy outcome was excellent functional outcome at 3months, defined as a score of 0-1 on the modified Rankin Scale. Our primary safety outcomes were symptomatic intracranial hemorrhage and all-cause mortality. Thirty-six studies were eligible for review, including 12 randomized (n = 5533) and 24 non-randomized studies (n = 44,956). Moderate certainty evidence showed that there was no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3months (odds ratio [OR], 1.10; 95% CI 0.98-1.23; risk difference [RD] 2.4%, 95% CI - 0.5 to 5.2), while moderate certainty evidence from NMA suggested that 0.25mg/kg tenecteplase significantly improved excellent functional outcome at 3months (OR, 1.16; 95% credible interval 1.02-1.32). Moderate certainty evidence showed that, compared to alteplase, tenecteplase may make little to no difference in the prevalence of symptomatic intracranial hemorrhage (OR, 1.12; 95% CI 0.79-1.59; RD 0.3%, 95% CI - 0.5 to 1.4), and probably reduces all-cause mortality (adjusted odds ratio [aOR], 0.44; 95% CI 0.30-0.64; RD - 4.6%; 95% CI - 5.8 to - 2.9). Moderate certainty evidence suggested that there was little to no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3months and the risk of symptomatic intracranial hemorrhage, while compared to alteplase, tenecteplase probably reduce all-cause mortality. Administration of 0.25mg/kg tenecteplase after acute ischemic stroke is suggestive of increasing the proportion of patients that achieve excellent functional outcome at 3months.

Abstract 24: Differences in Door to Needle and Door In Door Out Times for Tenecteplase vs Alteplase in Acute Ischemic Stroke: Findings From Get With the Guidelines Stroke

Introduction: Tenecteplase (TNK) has arisen as an alternative to alteplase (ALT) for emergent treatment of acute ischemic stroke. Shorter times to prepare and administer TNK raises the possibility that TNK use leads to faster treatment and transfer times. Hypothesis: We hypothesized that treatment with TNK is associated with shorter door-to-needle (DTN) and door-in-door-out (DIDO) times. Methods: Using the US Get With The Guidelines-Stroke registry, we performed a retrospective, observational cohort study of consecutive patients treated with either TNK or ALT between July 1, 2020 and June 30, 2022. The exposure was treatment with TNK vs ALT. The primary endpoints were DTN and DIDO. We fit generalized linear mixed models to determine the association between TNK (vs ALT) and endpoints after adjustment for key demographic, clinical, and hospital-level variables. A secondary analysis compared changes in DTN among hospitals that switched to TNK in 2021 with at least 10 cases per year pre and post switch. Results: From 2092 sites, 133,228 patients received intravenous thrombolysis. Among the 13,988 (10%) treated with TNK, median age was 70 yrs, median NIHSS 7, 47% female, 21% received endovascular thrombectomy (EVT), and 9% were transferred from the hospital emergency department after receiving lytic. Among 119,240 (90%) treated with ALT, median age was 69 yrs, median NIHSS 7, 48% female; 17% received EVT, and 12% were transferred after lytic. In the primary DTN analysis, time to treatment was shorter with TNK, with mean 47.0 vs 52.7 minutes and DTN ≤60 mins in 77.5% vs 70.7% (TABLE). In the primary DIDO analysis, time to departure was shorter with TNK, 108.3 vs 114.1 minutes. In centers that changed from ALT to TNK during this period DTN times were significantly lower after switching. Conclusions: In this largest study of TNK vs ALT workflow time intervals in ischemic stroke using population-based data, TNK use was associated with more favorable DTN and DIDO times relative to ALT use.

Reteplase versus alteplase for acute ischaemic stroke within 4.5 hours (RAISE): rationale and design of a multicentre, prospective, randomised, open-label, blinded-endpoint, controlled phase 3 non-inferiority trial

Background and purposeReteplase is the third generation of alternative thrombolytic agent. We hypothesis that reteplase will be non-inferior to alteplase in achieving excellent functional outcome at 90 days among eligible...

External Validation and Updating of Published Models for Predicting 7-day Risk of Symptomatic Intracranial Hemorrhage after Receiving Alteplase for Acute Ischemic Stroke: A Retrospective Cohort Study.

Prediction scores for symptomatic intracranial hemorrhage (sICH) in acute ischemic stroke patients receiving thrombolytic therapy have been widely developed, but the external validation of these scores, especially in the Thai population, is lacking. This study aims to externally validate existing models and update the selected model to enhance its performance in our specific context. This cohort study retrospectively collected data from medical records between 2013 and 2022. Acute ischemic stroke patients who received thrombolysis were included. All predictors were gathered at admission. External validation was performed on eight published prediction models; in addition, the observed and expected probabilities of sICH were compared. The most effective model for discrimination was then chosen for further updating using multivariable logistic regression and was bootstrapped for internal validation. Finally, a points-based system for clinical practice was developed from the optimism-corrected model. Fifty patients (10% of the 502 included cohort members) experienced sICH after undergoing thrombolysis. The SICH score outperformed the other seven models in terms of discrimination (area under the receiver operating characteristic [AuROC] curve = 0.74 [95% confidence interval {CI} 0.67 to 0.81]), but it still overstated risk (expected-to-observed outcomes [E/O] ratio = 1.7). Once updated, the optimism-corrected revised SICH model showed somewhat better calibration (E/O = 1 and calibration-in-the-large = 0), slightly worse underprediction in the moderate-to-high risk group (calibration slope = 1.152), and marginally better discrimination (AuROC = 0.78). The points-based system also demonstrated substantial agreement (88.1%) with the risk groups predicted by the logistic regression model (kappa statistic = 0.78). Since the SICH score outperformed seven models in terms of discrimination, it was then modified to the Revised-SICH score, which predicted that patients with at least 5.5 points were at high risk of having sICH.

Tenecteplase versus alteplase for patients with acute ischemic stroke: a meta-analysis of randomized controlled trials.

Tenecteplase (TNK), a newer fibrinolytic agent with greater fibrin specificity and longer half-life than alteplase, may has practical advantages over alteplase in acute ischemic stroke (AIS) thrombolysis. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare different doses of TNK (0.1, 0.25, 0.4 mg/kg) and alteplase in acute ischemic stroke patients. We systematically searched PubMed, Embase and https://clinicaltrials.gov/ for RCTs comparing TNK with alteplase in this population eligible for thrombolysis. The Cochrane Risk of Bias Tool was used to assess study quality. Random-effects or fixed-effects meta-analysis models were used for evaluating all outcomes. Total 10 RCTs with 5097 patients were included. Compared with alteplase, TNK at doses of 0.25 mg/kg may associated with the greatest odds to achieve 90-day excellent independence (mRS score ≤1), but there were no significant differences between other doses of TNK (0.1 mg/kg and 0.4 mg/kg) and alteplase. Among secondary outcomes, no significant differences were found in functional outcome (mRS score ≤2) and mortality at 90 days between any dose of TNK and alteplase. Compared with alteplase, TNK was effective at doses of 0.1 mg/kg and 0.25 mg/kg without increased risk of symptomatic intracerebral hemorrhage (sICH), but patients treated with TNK 0.4 mg/kg showed increased odds of sICH. In conclusion, compared with alteplase, intravenous thrombolysis with TNK at dose of 0.25 mg/kg has a better efficacy and similar safety profile and is a reasonable option for patients with AIS.

Risk of Bleeding Following Non–Vitamin K Antagonist Oral Anticoagulant Use in Patients With Acute Ischemic Stroke Treated With Alteplase

Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral anticoagulants (NOACs). To evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs. This nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan's National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO. NOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment. The primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model. Of the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, -4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, -2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, -4.95% [95% CI, -10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score-matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis. In this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.

Predictive role of admission serum glucose, baseline NIHSS score, and fibrinogen on hemorrhagic transformation after intravenous thrombolysis with alteplase in acute ischemic stroke.

This study aimed to investigate the predictive role of admission serum glucose, baseline NIHSS score, and fibrinogen on hemorrhagic transformation after intravenous thrombolysis with alteplase in acute ischemic stroke. A total of 254 patients admitted with acute ischemic stroke who received intravenous thrombolysis with alteplase from January 2016 to December 2017 were selected to collect clinical data. Patients were divided into a hemorrhagic transformation group (n=70) and a no-hemorrhagic transformation group (n=184) based on repeat CT/magnetic resonance imaging (MRI) findings during the acute period. The demographic data, past medical history and laboratory examination indexes of the two groups were compared. Multivariate Logistic regression analysis was used to explore the influencing factors of hemorrhage transformation after intravenous thrombolysis in patients with acute ischemic stroke. ROC curve was used to plot the ability of blood glucose at admission, baseline NIHSS score and fibrinogen alone to predict bleeding transformation after intravenous thrombolysis of alteplase, and then the combined model of the three was constructed and the predictive ability of this model to bleeding transformation was evaluated. Among 254 patients, 70% (27.55%) had hemorrhage transformation. Except for DNT, red blood cell count, platelet count, fibrinogen, smoking, atrial fibrillation, baseline NIHSS score and admission serum glucose, there were statistically significant differences between the hemorrhagic transformation group and the non-hemorrhagic transformation group (p<0.05), and there were no statistically significant differences in other indicators between the two groups (p>0.05). The combined model was better than the three models alone in predicting the risk of bleeding conversion (p<0.05). Compared with the group without hemorrhagic transformation, the 90d prognosis was worse in the hemorrhage transformation group (p<0.05). Admission blood glucose, NIHSS score, and fibrinogen are independent risk factors for hemorrhage transformation after intravenous thrombolysis of alteplase in patients with acute ischemic stroke, and the combined model established by them has high predictive efficacy for hemorrhage transformation risk after intravenous thrombolysis of alteplase.

Evaluation of Glycemic Variability and Discharge Outcomes in Patients with Ischemic Stroke Following Thrombolysis

Background and Purpose Hyperglycemia following acute ischemic stroke (AIS) is associated with adverse outcomes including, hemorrhagic conversion and increased length of stay; however, the impact of glycemic variability is largely unknown. This study aims to evaluate the effect of glycemic variability on discharge outcomes in patients treated with alteplase for AIS. Methods A retrospective review of ischemic stroke patients who presented within 4.5 hours from symptom onset and received alteplase was completed. Patients hospitalized for at least 48 hours were included. Glycemic variability was measured using J-index. Groups were defined by normal or abnormal J-indices. Logistic regression models were developed to determine odds ratios for select clinical characteristics, NIHSS score, mRS, and disposition at discharge. Results Of the 229 patients, 97 (42%) had an abnormal J-index. In the univariate analysis, abnormal J-index was associated with worse outcomes in terms of NIHSS score, mRS, and discharge disposition compared to a normal J-index. In the unadjusted multivariate analysis, abnormal J-index was associated with higher odds of unfavorable mRS (3-6) at discharge (OR 2.1; 95% CI 1.2 – 3.5, P = .009). In the adjusted multivariate analysis, patients with an abnormal J-index had higher odds of hemorrhagic transformation (OR 5.7; 95% CI 2.1 – 15.6, P &lt; .0001). There was no difference in mortality. Conclusion Glycemic variability with abnormal J-index following AIS is associated with adverse functional outcomes at discharge and increased odds of hemorrhagic conversion in patients treated with alteplase. Additional studies validating glycemic variability indices post-ischemic stroke are needed to determine the full clinical impact.

Urgent need for the introduction of Tenecteplase in Pakistan: A Call to action for improved stroke and Mi Care.

Madam, Tenecteplase is a recombinant tissue plasminogen activator (tPA) that is used in many countries worldwide for reperfusion in acute ischemic stroke (AIS) and STEMI because of its longer half-life and high fibrin specificity compared to other tPAs (e.g., alteplase) and Streptokinase.1 Tenecteplase binds with fibrin-rich clots using its fibronectin finger-like and kringle-2 domains. The binding allows the protease domain to cleave the Arg/Val bond, converting plasminogen into plasmin, which breaks the fibrin matrix of the thrombus, resulting in clot dissolution. While Stroke and MI remain in the top 5 leading causes of death in Pakistan2, this highly efficient thrombolytic agent is not yet accessible in most hospitals for reperfusion in acute ischemic stroke and myocardial infarction cases. Many studies offer promising results, with tenecteplase being a better thrombolytic agent for acute ischemic stroke and STEMI than alteplase. In India, studies declare tenecteplase effective and safe in STEMI patients with clinically successful thrombolysis reported in 80.67% of patients, while intracranial hemorrhage associated with tenecteplase was only 0.39%.3 Tenecteplase is more efficient and at least as safe as alteplase for acute ischemic stroke. According to a meta-analysis involving 2031 patients, the patients given Tenecteplase showed higher recanalization rates (ARD=0.11, 95%CI) and early neurological improvement (ARD=0.10, 95% CI) compared to patients given alteplase.4 Tenecteplase also has a lower cost and a more favorable pharmacokinetic profile allowing bolus injection. Regrettably, Tenecteplase is not yet accessible in Pakistan due to unclear political and administrative factors, and border restrictions. Studies claim that only six hospitals in Pakistan currently offer intravenous thrombolytic therapy with alteplase, all being private tertiary care hospitals.5 While the world is adopting Tenecteplase instead of alteplase because of its better results, a more favourable side effects profile, and lower cost, our healthcare system is still dependent on SK for IV thrombolysis in cases of STEMI, which too is sometimes not available in many hospitals. In light of available evidence suggesting Tenecteplase as a better alternative to alteplase and Streptokinase, the health government and hospital policymakers should consider introducing tenecteplase in Pakistan as the standard care for STEMI, New Onset LBBB (Left Bundle Branch Block), Acute Ischemic Stroke, Prosthetic Valve Thrombosis, Pulmonary Embolism, and Deep Venous Thrombosis.

Prourokinase Found Non-inferior to Alteplase for Acute Ischemic Stroke

Prourokinase Found Non-inferior to Alteplase for Acute Ischemic Stroke

Tenecteplase versus alteplase for acute ischaemic stroke: a meta-analysis of phase III randomised trials

BackgroundTenecteplase (TNK) was found non-inferior to alteplase in recent clinical trials. We aimed to elucidate the efficacy and safety of TNK versus alteplase for acute ischaemic stroke (AIS).MethodsSystematic literature search...

Safety and Efficacy of Tenecteplase Compared With Alteplase in Patients With Large Vessel Occlusion Stroke

It is unknown whether intravenous thrombolysis using tenecteplase is noninferior or preferable compared with alteplase for patients with acute ischemic stroke. To examine the safety and efficacy of tenecteplase compared to alteplase among patients with large vessel occlusion (LVO) stroke. This was a prespecified analysis of the Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada (ACT) randomized clinical trial that enrolled patients from 22 primary and comprehensive stroke centers across Canada between December 10, 2019, and January 25, 2022. Patients 18 years and older with a disabling ischemic stroke within 4.5 hours of symptom onset were randomly assigned (1:1) to either intravenous tenecteplase or alteplase and were monitored for up to 120 days. Patients with baseline intracranial internal carotid artery (ICA), M1-middle cerebral artery (MCA), M2-MCA, and basilar occlusions were included in this analysis. A total of 1600 patients were enrolled, and 23 withdrew consent. Intravenous tenecteplase (0.25 mg/kg) vs intravenous alteplase (0.9 mg/kg). The primary outcome was the proportion of modified Rankin scale (mRS) score 0-1 at 90 days. Secondary outcomes were an mRS score from 0 to 2, mortality, and symptomatic intracerebral hemorrhage. Angiographic outcomes were successful reperfusion (extended Thrombolysis in Cerebral Infarction scale score 2b-3) on first and final angiographic acquisitions. Multivariable analyses (adjusting for age, sex, National Institute of Health Stroke Scale score, onset-to-needle time, and occlusion location) were carried out. Among 1577 patients, 520 (33.0%) had LVO (median [IQR] age, 74 [64-83] years; 283 [54.4%] women): 135 (26.0%) with ICA occlusion, 237 (45.6%) with M1-MCA, 117 (22.5%) with M2-MCA, and 31 (6.0%) with basilar occlusions. The primary outcome (mRS score 0-1) was achieved in 86 participants (32.7%) in the tenecteplase group vs 76 (29.6%) in the alteplase group. Rates of mRS 0-2 (129 [49.0%] vs 131 [51.0%]), symptomatic intracerebral hemorrhage (16 [6.1%] vs 11 [4.3%]), and mortality (19.9% vs 18.1%) were similar in the tenecteplase and alteplase groups, respectively. No difference was noted in successful reperfusion rates in the first (19 [9.2%] vs 21 [10.5%]) and final angiogram (174 [84.5%] vs 177 [88.9%]) among 405 patients who underwent thrombectomy. The findings in this study indicate that intravenous tenecteplase conferred similar reperfusion, safety, and functional outcomes compared to alteplase among patients with LVO.

Tenecteplase: A Review of Its Pharmacology and Uses.

Tenecteplase: A Review of Its Pharmacology and Uses.

Tenecteplase to Replace Alteplase? Comparing Thrombolytic Therapies for Acute Ischemic Stroke: June 2023 Annals of Emergency Medicine Journal Club.

Tenecteplase to Replace Alteplase? Comparing Thrombolytic Therapies for Acute Ischemic Stroke: June 2023 Annals of Emergency Medicine Journal Club.