The treatment effect across ASPECTS in acute ischemic stroke: Analysis from the AcT Trial.

BACKGROUND: Early ischemic changes on baseline imaging are commonly evaluated for acute stroke decision-making and prognostication. AIMS: We assess the association of early ischemic changes on clinical outcomes and whether it differs between intravenous tenecteplase versus Alteplase. METHODS: Data are from the phase 3, Alteplase compared to Tenecteplase (AcT) trial. Subjects with anterior circulation stroke were included. Early ischemic changes were assessed using the Alberta Stroke Program Early CT score (ASPECTS). Efficacy outcomes included modified Rankin scale (mRS) 0-1, mRS 0-2, and ordinal mRS at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage (sICH), any hemorrhage on follow-up scan, and 90-day mortality rate. Mixed effects logistic regression was used to assess the association of ASPECTS [continuous and categorical (0-4 vs. 5-7 vs. 8-10)] with outcomes and if these associations were modified by thrombolytic type after adjusting for age, sex, and baseline stroke severity. RESULTS: Of the 1577 patients in the trial, 901 patients (56.3%) (median age 75 years [IQR 65-84], 50.8% females, median NIHSS 14 [IQR 17-19]) with anterior circulation stroke were included. mRS 0-1 at 90d was achieved in 1/14 (0.3%), 43/160 (14.7%) and 252/726 (85.1%) in the ASPECTS 0-4, 5-7 and 8-10 groups respectively. Every 1-point decrease in ASPECTS was associated with 2.7% and 1.9% decrease in chances of mRS 0-1 and mRS 0-2 at 90 days, respectively, and 1.9% chances of increase in mortality at 90 days. Subgroup analysis in EVT treated population showed similar results. Thrombolytic type did not modify this association between ASPECTS and 90-day mRS 0-1 (P interaction 0.75). There was no significant interaction by thrombolytic type with any other outcome. CONCLUSIONS: Similar to prior studies, we found that every one-point decrease in ASPECTS was associated with poorer clinical and safety outcomes. This effect did not differ between alteplase and tenecteplase.

Comparison of Tenecteplase Versus Alteplase for the Treatment of Pulmonary Embolism and Cardiac Arrest with Suspected Pulmonary Embolism.

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.

Ultrasound and Intrapleural Enzymatic Therapy for Complicated Pleural Effusion: A Case Series with a Literature Review.

Pleural effusion is the most common manifestation of pleural disease, and chest ultrasound is crucial for diagnostic workup and post-treatment monitoring. Ultrasound helps distinguish the various types of pleural effusion and enables the detection of typical manifestations of empyema, which presents as a complicated, septated effusion. This may benefit from drainage and the use of intrapleural enzyme therapy or may require more invasive approaches, such as medical or surgical thoracoscopy. The mechanism of action of intrapleural enzymatic therapy (IPET) is the activation of plasminogen to plasmin, which breaks down fibrin clots that form septa or the loculation of effusions and promotes their removal. In addition, IPET has anti-inflammatory properties and can modulate the immune response in the pleural space, resulting in reduced pleural inflammation and improved fluid reabsorption. In this article, we briefly review the literature on the efficacy of IPET and describe a case series in which most practical applications of IPET are demonstrated, i.e., as a curative treatment but also as an alternative, propaedeutic, or subsequent treatment to surgery.

Early Recanalization after Tenecteplase versus Alteplase: Experience in a Large Stroke Network.

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.

Systolic blood pressure and early neurological deterioration in minor stroke: A post hoc analysis of ARAMIS trial.

BACKGROUND: Systolic blood pressure (SBP) was a predictor of early neurological deterioration (END) in stroke. We performed a secondary analysis of ARAMIS trial to investigate whether baseline SBP affects the effect of dual antiplatelet versus intravenous alteplase on END. METHODS: This post hoc analysis included patients in the as-treated analysis set. According to SBP at admission, patients were divided into SBP ≥140 mmHg and SBP <140 mmHg subgroups. In each subgroup, patients were further classified into dual antiplatelet and intravenous alteplase treatment groups based on study drug actually received. Primary outcome was END, defined as an increase of ≥2 in the NIHSS score from baseline within 24 h. We investigated effect of dual antiplatelet vs intravenous alteplase on END in SBP subgroups and their interaction effect with subgroups. RESULTS: A total of 723 patients from as-treated analysis set were included: 344 were assigned into dual antiplatelet group and 379 into intravenous alteplase group. For primary outcome, there was more treatment effect of dual antiplatelet in SBP ≥140 mmHg subgroup (adjusted RD, -5.2%; 95% CI, -8.2% to -2.3%; p < 0.001) and no effect in SBP <140 mmHg subgroup (adjusted RD, -0.1%; 95% CI, -8.0% to 7.7%; p = 0.97), but no significant interaction between subgroups was found (adjusted p = 0.20). CONCLUSIONS: Among patients with minor nondisabling acute ischemic stroke, dual antiplatelet may be better than alteplase with respect to preventing END within 24 h when baseline SBP ≥140 mmHg.

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

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

Baseline neurological deficit and argatroban plus alteplase in acute ischemic stroke: A post hoc analysis of ARAIS trial.

BACKGROUND: The ARAIS trial didn't demonstrate argatroban significantly improve functional outcome at 90 days in acute ischemic stroke. We conducted post hoc analysis of ARAIS to investigate whether baseline neurological deficit was associated with outcomes. METHODS: Patients without endovascular therapy who met screening criteria as protocol and completed argatroban treatment were enrolled and classified into two subgroups according to NIHSS score at admission. Primary outcome was excellent functional outcome at 90 days, defined as mRS score of 0 to 1. Early neurological deterioration (END), defined as an increase of ≥4 in the NIHSS score from baseline within 48 hours, was investigated as secondary outcome. Compared with alteplase alone, we investigated treatment effect of argatroban plus alteplase on outcomes in subgroups and interaction with subgroups. RESULTS: A total of 675 patients from full analysis set were included: 390 were assigned into NIHSS score <10 subgroup and 285 into NIHSS score ≥10 subgroup. For primary outcome, there was similar treatment effect between argatroban plus alteplase and alteplase alone in NIHSS score ≥10 subgroup (adjusted RD, 5.8%; 95% CI, -6.0% to 17.5%; P = 0.33) and in NIHSS score <10 subgroup (adjusted RD, -1.4%; 95% CI, -9.9% to 7.1%; P = 0.75), and no significant interaction (P = 0.43). Occurrence of early neurological deterioration within 48 hours were significantly lower in NIHSS score ≥10 subgroup, compared with NIHSS score <10 subgroup (P = 0.006). CONCLUSION: Among patients with NIHSS score ≥10, argatroban plus alteplase could safely reduce END within 48 hours.

Comparative efficacy and safety among different doses of tenecteplase for acute ischemic stroke: A systematic review and network meta-analysis.

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.

Variables Leading to Usage of Alteplase Versus Heparin Lock in Patients With Tunneled Catheters in Hemodialysis Care Project Centers, Saudi Arabia.

INTRODUCTION: A hemodialysis tunneled catheter is one option for vascular access used with hemodialysis patients; however, catheter complications such as thrombosis are still inevitable. To prevent thrombosis formation, a catheter-locking solution is instilled between dialysis sessions. Heparin is used as a default locking solution in our Hemodialysis Care Project centers, while a recombinant tissue plasminogen activator (rt-PA) such as alteplase is used to treat suspected catheter thrombosis. This study aimed to identify the clinical factors, catheter brands, and hemodialysis variables that influence the choice of use for alteplase versus heparin, for those patients with tunneled catheters, and reduce overprescribing of high-alert medication alteplase. METHODS: A retrospective medical chart review study was conducted involving 230 patients with tunneled catheters; the first group of 133 patients used alteplase regularly three times a week, while the second group of 97 patients completed at least one year using the same catheter access with heparin lock only. RESULTS: Multivariate logistic regression and logistic regression analysis showed a significant association (p < 0.05) between different variables. Results suggest that overweight and hyperlipidemia patients are more likely to use alteplase. Patients using brand-name catheters such as Hemostar/Vas-cath (BD, Franklin Lakes, NJ) are less likely to use heparin than those using Medcomp catheters (Medcomp, Yuma, AZ). In addition, patients having a history of angioplasty would be less likely to have heparin than no angioplasty. Moreover, if the patient's fluid removal were equal to or less than 2 kg, they would be more likely to use heparin and vice versa. CONCLUSION: The study postulates that identified variables affect whether alteplase or heparin is used in hemodialysis tunneled catheters, and may be useful to increase awareness, improve practices, or judiciously control the use of alteplase within Saudi Arabia and globally.

Clot migration in patients treated with tenecteplase versus alteplase before mechanical thrombectomy.

INTRODUCTION: This study aimed to describe and analyze the rate of clot migration of vessel thrombosis to distal segments in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis (IVT) with tenecteplase (TNK) and alteplase (ALT) before mechanical thrombectomy (MT). In addition, we aimed to determine the relationship between thrombus migration and functional prognosis. METHODS: This study followed the STROBE reporting guidelines. We performed a retrospective analysis of a series of patients from November 2017 to April 2023 with an AIS with thrombosis on CT imaging, treated with IVT (TNK or ALT, split into two distinct groups) prior to mechanical thrombectomy. RESULTS: Two hundred and fifty-six patients with large vessel occlusion (LVO) were included. Ninety-six had received TNK. One hundred and sixty had received ALT. Of the 96 TNK patients, 25 experienced either complete recanalization (n = 3) or thrombus migration (n = 22). Of the 160 ALT patients, 20 experienced either complete recanalization (n = 6) or thrombus migration (n = 14). The difference being statistically substantial for the thrombus migration rate (OR = 3.61, 95% confidence interval: 1.63; 7.98). Migration to an irretrievable very distal segment occurred in four (4%) patients with TNK and in three patients (2%) with ALT (p > 0.05). Thrombus migration was not significantly associated to a different functional prognosis, measured through Rankin scale after 3 months (OR = 0.44, 95% confidence interval: 0.17; 1.12). CONCLUSION: The use of TNK over ALT as a fibrinolytic agent is associated with a higher thrombus migration rate. The migration of thrombi to distal segments, which are theoretically less accessible for mechanical thrombectomy, did not result in worse clinical outcomes.

Door to needle time trends after transition to tenecteplase: A Multicenter Texas stroke registry.

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.

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.

Real-world data of tenecteplase vs. alteplase in the treatment of acute ischemic stroke: a single-center analysis.

Background: This retrospective observational cohort study aimed to evaluate whether tenecteplase's use for acute ischemic stroke (AIS) has time management advantages and clinical benefits. Methods: 144 AIS patients treated with alteplase and 120 with tenecteplase were included. We compared baseline clinical characteristics, key reperfusion therapy time indices [onset-to-treatment time (OTT), door-to-needle time (DNT), and door-to-puncture time (DPT)] and clinical outcomes (24-h post-thrombolysis NIHSS improvement, and intracranial hemorrhage incidence) between the groups using univariate analysis. We assessed hospital stay durations and used binary logistic regression to examine tenecteplase's association with DNT and DPT target times, NIHSS improvement, and intracranial hemorrhage. Results: Baseline characteristics showed no significant differences except hyperlipidemia and atrial fibrillation. OTT (133 vs. 163.72, p = 0.001), DNT (36.5 vs. 50, p < 0.001) and DPT (117 vs. 193, p = 0.002) were significantly faster in the tenecteplase group. The rates of DNT ≤ 45 min (65.83% vs. 40.44%, p < 0.001) and DPT ≤ 120 min (59.09% vs. 13.79%, p = 0.001) were significantly higher in the tenecteplase group. Tenecteplase was an independent predictor of achieving target DNT (OR 2.951, 95% CI 1.732-5.030; p < 0.001) and DPT (OR 7.867, 95% CI 1.290-47.991; p = 0.025). Clinically, the proportion NIHSS improvement 24 h post-thrombolysis was higher in the tenecteplase group (64.17% vs. 50%, p = 0.024). No significant differences were observed in symptomatic intracranial hemorrhage (sICH) or any intracranial hemorrhage (ICH). Patients receiving tenecteplase had shorter hospital stays (6 vs. 8 days, p < 0.001). Tenecteplase was an independent predictor of NIHSS improvement at 24 h (OR 1.715, 95% CI 1.011-2.908; p = 0.045). There was no significant association between thrombolytic choice and sICH or any ICH. Conclusion: Tenecteplase significantly reduced DNT and DPT. It was associated with early neurological function improvement (at 24 h), without compromising safety compared to alteplase. The findings support tenecteplase's application in AIS.

Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Systematic Review and Meta-analysis.

Background: A number of clinical trials have compared tenecteplase (TNK) and alteplase for the management of acute ischemic stroke (AIS) and the results are inconsistent. Purpose: Present systematic review and meta-analysis is undertaken to analyse the efficacy and safety of TNK in AIS compared to alteplase. Summary: A thorough literature search was performed through the databases Embase, Cochrane Library, PubMed, and clinicaltrials.gov, for a period from inception to September 2022, with the keywords i.e., "tenecteplase" and "alteplase" and "acute ischemic stroke." Clinical trials published in English that compared the efficacy and safety of TNK to alteplase in AIS were included. The major outcomes of this meta-analysis were proportion of patients free from disability and functional independence at 90 days, early neurological improvement at 24 hours, all-cause mortality at 90 days, patients with intra cranial hemorrhage (ICH), and patients with severe disability at 90 days. A total of nine studies with 3,573 patients were included in the analysis. The proportion of patients with freedom from disability was comparable in both groups (relative risk [RR] = 1.04, 95 per cent CI = 0.92-1.17; p = .53). Similarly, proportion of patients with functional independence was comparable (RR = 1.12, 95 per cent CI = 0.96-1.31; p = .14). TNK group had a higher rate of early neurological recovery (RR = 1.56, 95 per cent CI = 0.96-2.54; p = .07). All-cause mortality at 90 days was comparable in both groups (RR = 0.97; 95 per cent CI = 0.72-1.29; p = .82). The proportion of patients with ICH was higher in TNK group (RR = 1.14, 95 per cent CI = 0.77-1.68; p = .52). The proportion of patients with severe disability was less in TNK group (RR =0.84, 95 per cent CI = 0.53-1.32; p = .44). Key Message: TNK was similar to alteplase in terms of efficacy and safety. The patients in TNK group showed early neurological improvement but were simultaneously at higher risk of ICH. The TNK can be an alternative to alteplase if the benefits outweigh the risks.

Implementation of a Tenecteplase Protocol for Treatment of Acute Ischemic Stroke in a Health System.

Purpose. Alteplase is the standard of care for intravenous thrombolytic treatment of acute ischemic stroke, but recent evidence suggests that tenecteplase may be as safe and efficacious. The purpose of this study was to evaluate the direct cost savings, safety, and efficacy outcomes following the implementation of a tenecteplase protocol for acute ischemic stroke in the emergency departments within a health system. Methods. A multicenter retrospective medical record review was performed for 4 months prior to protocol implementation on patients who received alteplase and for 4 months post-implementation on patients who received tenecteplase. The primary outcome was the direct cost difference associated with tenecteplase. Secondary outcomes included reduction in National Institutes of Health Stroke Scale 24 hours after thrombolytic therapy, door-to-needle time, symptom onset to intravenous thrombolysis time, incidence of adverse effects, and death. Results. Pre-implementation, 102 received alteplase and post-implementation, 117 received tenecteplase. Four months of utilization of tenecteplase resulted in direct cost savings of $209,476.80 for the health system, which translates to roughly $2,000 per patient. Reduction in the National Institutes for Health Stroke Scale were similar between the two groups with -3.96 in alteplase and -3.18 in tenecteplase (p = 0.952). Median door-to-needle time was 44.5 minutes in alteplase and 49 minutes in tenecteplase. Adverse events occurred in 19 patients in alteplase and 19 in tenecteplase (p = 0.573). Death occurred in 9 patients in alteplase and 14 patients in tenecteplase (p = 0.376). Conclusion. A tenecteplase protocol was successfully implemented in the healthcare system resulting in direct cost savings with no significant differences in adverse events.

Comprehensive Review of Tenecteplase for Thrombolysis in Acute Ischemic Stroke.

Although intravenous thrombolysis with alteplase remains the primary treatment for acute ischemic stroke, tenecteplase has shown potential advantages over alteplase. Animal studies have demonstrated the favorable pharmacokinetics and pharmacodynamics of tenecteplase. Moreover, it is easier to administer. Clinical trials have demonstrated that tenecteplase is not inferior to alteplase and may even be superior in cases of acute ischemic stroke with large vessel occlusion. Current evidence supports the time and cost benefits of tenecteplase, suggesting that it could potentially replace alteplase as the main option for thrombolytic therapy, especially in patients with large vessel occlusion.

Spurious Hyperphosphatemia in Two Children With End-Stage Renal Disease: A Case Report.

Spurious hyperphosphatemia, also known as pseudo-hyperphosphatemia, refers to artifactually elevated serum phosphate values that do not correspond to their actual systemic levels. Vascular access poses a significant challenge for individuals undergoing hemodialysis (HD) due to chronic kidney disease, primarily attributed to the elevated incidence of complications, such as infections or thrombosis associated with catheter use. To mitigate clotting risk during the inter-dialysis intervals, in recent years, a strategy involving the application of concentrated heparin (recombinant tissue plasminogen activator (rt-PA) e.g. alteplase) has been used. These infusions have a very high content of phosphorus, and if it is not removed sufficiently before collecting blood samples through the central venous catheter, it can cause erroneously high phosphate levels. Here we report two cases of pseudo-hyperphosphatemia caused by contaminated blood samples obtained from an HD catheter from the pediatric nephrology department. Absurd values found in routine samples led us to investigate the reason for these results. Further investigations carried out by the laboratory biochemistry department showed that all the analytical checks and proficiency testing performance were within acceptable limits. We hypothesized that there was a pre-analytical error such as possible contamination with the high phosphate content of heparin and alteplase solution in the catheter, contributing to the increased phosphate levels in these samples.

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

OBJECTIVE: 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. METHODS: 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 3 months, defined as a score of 0-1 on the modified Rankin Scale. Our primary safety outcomes were symptomatic intracranial hemorrhage and all-cause mortality. RESULTS: 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 3 months (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 0.25 mg/kg tenecteplase significantly improved excellent functional outcome at 3 months (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). CONCLUSIONS: 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 3 months and the risk of symptomatic intracranial hemorrhage, while compared to alteplase, tenecteplase probably reduce all-cause mortality. Administration of 0.25 mg/kg tenecteplase after acute ischemic stroke is suggestive of increasing the proportion of patients that achieve excellent functional outcome at 3 months.

Intrapleural Fibrinolysis with Urokinase versus Alteplase in Complicated Pleural Effusions and Empyema: A Prospective Randomized Controlled Trial.

BACKGROUND: Intrapleural fibrinolytic therapy (IPFT) has been used as an effective agent since 1949 for managing complicated pleural effusion and empyema. Several agents, such as streptokinase, urokinase (UK), and recombinant tissue plasminogen activator (rt-PA), have been found to be effective with variable effectiveness. However, a head-tohead controlled trial comparing the efficacy of the most frequently used agents, i.e., UK and rt-PA (alteplase) for managing complicated pleural effusion has rarely been reported. METHODS: A total of 50 patients were randomized in two intervention groups, i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac units. UK was given thrice daily for 2 days, followed by clamping to allow the retainment of drugs in the pleural space for 2 hours. rt-PA was instilled into the pleural space twice daily for 2 days, and intercostal drainage was clamped for 1 hour. RESULTS: A total of 50 patients were enrolled into the study, of which 84% (n=42) were males and 16% (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The percentage of mean± standard deviation changes in pleural opacity was -33.0%±9.9% in the UK group and -41.0%±14.9% in the alteplase group, respectively (p=0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and in 40% (n=8) of the patients in the alteplase group (p=0.24), while fever was the second most common side effect. Patients who reported early (within 6 weeks of onset of symptoms) showed a greater response than those who reported late for the intervention. CONCLUSION: IPFT is a safe and effective option for managing complicated pleural effusion or empyema, and newer agents, such as alteplase, have greater efficacy and a similar adverse effect profile when compared with conventional agents, such as UK.