Safety Of Tenecteplase Research Articles

Emerging therapies in the management of acute ischemic stroke: Innovative approaches and clinical outcomes- A comprehensive literature review

Worldwide, acute ischemic stroke continues to be the primary cause of death and disability, requiring ongoing improvements in treatment approaches. With an emphasis on current advancements in collateral evaluation, thrombolytic therapy, endovascular thrombectomy, and neuroprotective treatment, this review examines novel treatments for acute ischemic stroke. To find relevant research published in the past five years, a thorough search of academic databases was carried out. The inclusion criteria for the inclusion of articles on innovative therapeutics and their implications for managing acute stroke were methodological rigor and direct relevance. With an emphasis on the effectiveness and safety of Tenecteplase, the review emphasizes the crucial role that collateral circulation plays in forecasting patient response to reperfusion treatments and the changing landscape of thrombolytic drugs. Furthermore, the treatment of acute strokes has been transformed by developments in endovascular thrombectomy, which provides better functional results for patients with major artery occlusions. Additionally, neuroprotective drugs have potential as complementary treatments, especially when used in combination with reperfusion procedures. Novel treatments for acute ischemic stroke provide fresh chances to improve patient outcomes and lower stroke-related morbidity and death. To provide equal access to improved stroke care, solve outstanding difficulties, and enhance treatment regimens, further research is required.

Tenecteplase, 0.4 mg/kg, in Moderate and Severe Acute Ischemic Stroke: A Pooled Analysis of NOR-TEST and NOR-TEST 2A.

Background The optimal dose of tenecteplase in acute ischemic stroke remains to be defined. We present a pooled analysis of the 2 NOR-TESTs (Norwegian Tenecteplase Stroke Trials) exploring the efficacy and safety of tenecteplase, 0.4 mg/kg. Methods and Results We retrospectively reviewed 2 PROBE (Prospective Randomized Open, Blinded End-point) trials, NOR-TEST and NOR-TEST 2A. Patients were randomized to either tenecteplase, 0.4 mg/kg, or alteplase, 0.9 mg/kg. The primary end point was favorable functional outcome at 3 months (modified Rankin Scale score, 0-1) or return to baseline if prestroke modified Rankin Scale score was 2. Secondary end points included favorable functional and clinical outcome and safety data. The pooled analysis includes patients with National Institutes of Health Stroke Scale score ≥6 from both trials and an additional post hoc analysis of patients with National Institutes of Health Stroke Scale score ≤5 from NOR-TEST. The per-protocol analysis contains 483 patients, of whom 235 were assigned to tenecteplase and 248 were assigned to alteplase. In per-protocol analysis, functional outcome was better in the alteplase arm with cutoff modified Rankin Scale score of 2 (odds ratio [OR], 0.52 [95% CI, 0.33-0.80]; P=0.003) and expressed by ordinal shift analysis (OR, 1.64 [95% CI, 1.17-2.28]; P=0.004). Mortality at 3 months was higher in the tenecteplase arm (OR, 2.48 [95% CI, 1.20-5.10]; P=0.01). Mortality and intracranial hemorrhage rates were higher in the severe stroke group randomized to tenecteplase, whereas these rates were similar for alteplase and tenecteplase in moderate and mild stroke. Conclusions Tenecteplase, 0.4 mg/kg, is unsafe in moderate and severe stroke, and the risk of death and intracranial hemorrhage probably increases with stroke severity. A lower tenecteplase dose should be tested in future trials. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01949948, NCT03854500.

Tenecteplase: A Review of Its Pharmacology and Uses.

Tenecteplase: A Review of Its Pharmacology and Uses.

Comparative Efficacy and Safety of Tenecteplase and Alteplase in Acute Ischemic Stroke: A Pairwise and Network Meta-analysis of Randomized Controlled Trials (S45.002)

<h3>Objective:</h3> We aim to conduct a dose-wise comparison of tenecteplase and alteplase on various efficacy and safety outcomes in patients with acute ischemic stroke. <h3>Background:</h3> Randomized controlled trials (RCTs) exploring the comparative efficacy and safety of tenecteplase and alteplase have been yielding contradictory results on various outcomes. Previous studies have also failed to conduct a dose-wise comparison; this meta-analysis stratifies doses in order to refine our interpretation of outcomes and quantify the benefits and harms of tenecteplase at different doses. <h3>Design/Methods:</h3> PubMed/MEDLINE, Cochrane Controlled Register of Trials, and reference lists of the included articles were systematically searched for article retrieval. Several efficacy and safety outcomes were assessed via DerSimonian and Laird random-effects model and reported as Relative Risk at 95% Confidence Interval. Network analysis allowed for a better comparison of doses via indirect collation. Regression analysis was run to identify how outcomes may vary for differing baseline NIHSS scores. <h3>Results:</h3> Ten randomized controlled trials with a total of 4140 patients were included. 2166 (52.32%) patients were enrolled in the tenecteplase group and 1974 (47.68%) in the alteplase group. Tenecteplase at 0.25 mg/kg dose demonstrated significant improvement in excellent functional outcome at 3 months (RR 1.14, 95% CI 1.04–1.26), and early neurological improvement (RR 1.53, 95% CI 1.03–2.26). There was no statistically significant difference between tenecteplase and alteplase in terms of good functional outcome, intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality at any dose. Regression analysis demonstrated no significant impact of baseline NIHSS score on functional outcome and mortality. <h3>Conclusions:</h3> Tenecteplase at 0.25 mg/kg dosage is more efficacious and at least as safe as alteplase for stroke thrombolysis. Newer analyses need to focus on direct comparison of tenecteplase doses and whether tenecteplase is efficacious at longer needle times. <b>Disclosure:</b> Mr. Rehman has nothing to disclose. Mr. Aemaz Ur Rehman has nothing to disclose. Miss Mohsin has nothing to disclose. Dr. Cheema has nothing to disclose. Miss Zahid has nothing to disclose. Mr. Ebaad Ur Rehman has nothing to disclose. Mr. Ameer has nothing to disclose. Mr. Ayyan has nothing to disclose. Mr. Ehsan has nothing to disclose. Ms. Shahid has nothing to disclose. Dr. Khawaja has nothing to disclose.

Intravenous Thrombolytics in the Treatment of Acute Ischemic Stroke

To review the current evidence and ongoing clinical trials evaluating the efficacy and safety of tenecteplase (TNK), an alternative tissue plasminogen activator (tPA), in the acute management of arterial ischemic stroke (AIS). To date, alteplase is the only tPA approved by the United States FDA for use in AIS. There have been multiple phase two and three trials investigating the safety and efficacy of TNK in AIS. In patients with AIS due to large vessel occlusion, one randomized controlled trial demonstrated superiority of TNK for vessel recanalization rates and long-term functional outcomes when compared to alteplase. A meta-analysis of all phase two and three trials evaluating TNK in AIS concluded that TNK has a comparable safety and efficacy profile to alteplase. The results of these trials prompted new recommendations in the Acute Stroke Guideline published by the AHA suggesting it may be reasonable to use as an alternative to alteplase. Furthermore, recent real-world data has also reported decreased door-to-needle time with TNK utilization. In patients with AIS, use of a thrombolytic agent is standard of care and has been shown to reduce neurological disability and improve functional outcome. Randomized controlled trials have demonstrated that TNK is non-inferior to alteplase from a clinical outcome and safety standpoint. The existing data evaluating the efficacy of TNK compared to alteplase in acute AIS within 4.5h from symptom onset showed no significant difference between these two agents with regard to functional outcome at 90days but improved median time to treatment and large vessel recanalization in TNK-treated patients. The results from ongoing TNK trials in larger patient cohorts and in wake-up stroke populations will be instrumental to the wide-scale utilization of TNK in acute AIS management.

IV tenecteplase: A non-inferior alternative to alteplase?

The standard medical therapy for intravenous thrombolysis in patients with stroke presenting within 3h is alteplase, a tissue plasminogen activator. Menon and colleagues assessed the non-inferiority, efficacy, and safety of tenecteplase, a modified version of alteplase, in patients with acute ischemic stroke presenting within 4.5h of onset.

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

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

Advances in Stroke: Treatments-Interventional.

Advances in Stroke: Treatments-Interventional.

Tenecteplase versus alteplase for acute ischemic stroke thrombolysis: a systematic review and meta-analysis

Background: Intravenous thrombolysis is the preferred clinical treatment for acute ischemic stroke. Alteplase is an intravenous thrombolytic drug used in clinical practice. Recently, studies have shown the efficacy of another intravenous thrombolytic drug, tenecteplase, and have reported that the risk of bleeding is low. However, at present, Chinese and international research has yielded controversial results regarding the efficacy and risks of tenecteplase. Therefore, this systematic review and meta- analysis of the efficacy and safety of tenecteplase were performed. Methods: PubMed, the Cochrane Library, MEDLINE, the Wanfang Database and CNKI were searched for all studies on the thrombolytic treatment of acute ischemic stroke. All studies published in English prior to March 2021 were retrieved. The studies were screened and selected based on the inclusion and exclusion criteria. Then, the data were extracted and recorded by trained researchers. RevMan 5.4 statistical software was used to analyze the data on the 24h recanalization rate, early neurological improvement (24h reduction in the National Institutes of Health Stroke Scale [NIHSS] score of at least 8 points or 24 h NIHSS score of 0~1 point), mRS score at 90 days, intracranial hemorrhage, symptomatic intracranial hemorrhage and mortality in the tenecteplase group and alteplase group. Results: A total of 565 related studies were identified through the initial searches in each database. The citations of meta-analyses and related reviews were screened for additional eligible articles. Eventually, 9 high-quality English-language articles that included 2149 patients with acute ischemic stroke (including 1035 in the tenecteplase group and 1046 in the alteplase group)were included in this meta-analysis. The meta-analysis results were as follows: (1) Efficacy: The 24 h recanalization rate with regard to vascular recanalization was significantly better in the tenecteplase group than in the alteplase group(OR = 1.83, 95% CI: 1.23~2.72, z = 2.97, P = 0.003). There was significantly greater improvement in early neurological function in the tenecteplase group than in the alteplase group (OR= 1.34, 95% CI: 1.11~1.63, Z=3.00, P =0.003). There were no significant differences in 90-day mRS scores between the two groups (mRS score =0-1, OR = 1.20, 95% CI: 0.99~1.46, z = 1.82, p = 0.07; mRS score =0-2, OR = 1.17, 95% CI: 0.94~1.45, z = 1.38, p = 0.17). However, the subgroup analysis showed that the 90-day mRS score of the 0.25 mg/kg tenecteplase group was significantly different from that of groups treated with other doses of tenecteplase (OR = 1.48, 95% CI: 1.01~2.03, z = 2.03, p = 0.04). (2) Safety: The incidences of any intracranial hemorrhage (OR = 0.91, 95% Ci: 0.55~1.49, z = 0.39, p = 0.70), symptomatic intracranial hemorrhage (OR = 1.21, 95% CI: 0.63~2.32, z = 0.56 P = 0.57), and mortality (OR = 0.85, 95% CI: 0.57~1.26, z = 0.82, p = 0.41) were not significantly different between the tenecteplase and alteplase groups. Conclusions: Tenecteplase can significantly increase the 24-hour vascular recanalization rate and improve the neurological prognosis of patients with acute ischemic stroke and it does not increase the risk of intracranial hemorrhage or mortality.

Tenecteplase Versus Reteplase in Acute Myocardial Infarction: A Network Meta-Analysis of Randomized Clinical Trials.

Acute myocardial infarction (AMI) is the leading cause of death throughout the world. One of the standard approaches to treatment of AMI is fibrinolysis. The study was conducted to evaluate the clinical efficacy of tenecteplase versus reteplase through network meta-analysis for AMI. Randomized trials were comprehensively searched in PubMed, Scopus, Cochrane library, and Web of Science using appropriate strategies. Quality assessment was done for the papers. The primary and secondary end-points were mortality, TIMI grade 3 flow at 90 min, death or non-fatal stroke, infarction, total stroke and major bleeding. Odds ratios (OR) were computed (95% confidence intervals). After screening 27325 records, eight articles were included with total patients of 49875 to the meta-analysis. Indirect comparison of tenecteplase vs. reteplase showed no significant differences in the risk of mortality (OR = 0.98, p > 0.05), TIMI grade 3 flow at 90 min (OR = 0.77, p > 0.05), death or non-fatal stroke (OR = 1.04, p > 0.05), infarction (OR = 1.11, p > 0.05), total stroke (OR = 2.71, p > 0.05), and major bleeding (OR = 0.81, p > 0.05) (all p > 0.05). Indirect comparison suggests similar efficacy and safety of tenecteplase and reteplase. Hence, the use of each one of the two medicines depends on price, facility, and accessibility of the medicine.

Safety and predictors of stroke mimics in The Norwegian Tenecteplase Stroke Trial (NOR-TEST)

Stroke mimics are frequently treated with thrombolysis in clinical practice and thrombolytic trials. Although alteplase in stroke mimics has proven to be safe, safety of tenecteplase in stroke mimics has not been assessed in an ischemic stroke study setting. We aimed to assess clinical characteristics and safety of stroke mimics treated with thrombolysis in the Norwegian Tenecteplase Stroke Trial. We also aimed to identify possible predictors of stroke mimics as compared to patients with acute cerebral ischemia. Norwegian Tenecteplase Stroke Trial was a phase-3 trial investigating safety and efficacy of tenecteplase vs. alteplase in patients with suspected acute cerebral ischemia. Two groups were defined based on diagnose at discharge: patients with a different diagnose than ischemic stroke or transient ischemic attack (stroke mimics group) and patients diagnosed with ischemic stroke or transient ischemic attack (acute cerebral ischemia group). Logistic regression analyses were performed with stroke mimics vs. acute cerebral ischemia as dependent variable to identify predictors of stroke mimics. Of 1091 randomized patients, 181 (16.6%) were stroke mimics. Migraine (22.2%) and peripheral vertigo (11.4%) were the two most frequent stroke mimic-diagnoses. There was no symptomatic intracerebral hemorrhage in the stroke mimics group. Stroke mimics were independently associated with age ≤60 years (OR 2.75, p < 0.001), female sex (OR 1.48, p = 0.026), no history of myocardial infarction (OR 2.03, p = 0.045), systolic BP ≤ 150 mmHg (OR 2.33, p < 0.001), NIHSS ≤ 6 points (OR 1.83, p = 0.011), sensory loss (OR 1.55, p = 0.015), and no facial paresis (OR 2.41, p < 0.001) on admission. Thrombolysis with tenecteplase seems to be as safe as with alteplase in stroke mimics. Predictors were identified for stroke mimics which may contribute to differentiate stroke mimics from acute cerebral ischemia in future stroke trials.

Tenecteplase versus Alteplase for the Management of Acute Ischemic Stroke in a Low-income Country-Nepal: Cost, Efficacy, and Safety.

Intravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered, mutant tissue plasminogen activator, is an alternative thrombolytic agent. The economic feasibility of stroke treatment has been a matter of huge debate and discussion thus far. The use of thrombolytics for the management of ischemic stroke has recently begun in Nepal. In low-income countries like Nepal, where the per capita income falls at just $691.7 and 25.2% of the population are under the poverty line, stroke patients cannot meet treatment expenses. Tenecteplase is easily available (for the management of acute coronary syndrome) in tertiary-level hospitals of Nepal and the price quote of tenecteplase ($450) is half the price of alteplase ($1000). In emergency cases, sometimes, the cost of alteplase can be greater than the patient can afford and they can't undergo thrombolysis even after arriving on time. However, evidence exists that supports the use of other alternatives (tenecteplase), which are also effective in the management of acute ischemic stroke. In this article, we examined current evidence for the efficacy and safety of tenecteplase when compared to alteplase. This review will make neurologists in Nepal familiar with the efficacy and safety of tenecteplase in comparison with alteplase since it is common for patients to not be able to afford the expensive alteplase, which makes guideline-based practice impossible some times.

Tenecteplase compared with streptokinase and heparin in the treatment of pulmonary embolism: an observational study

Background: Thrombolytics are recommended in high risk patients with massive pulmonary embolism (PE). However, clinical practice seems to be far different and questions related to its utility in less severely affected patients remain the subject of investigation. The objective of this observational study was to compare the efficacy and safety of tenecteplase with streptokinase and heparin.Method: A total of 103 patients (tenecteplase: 62, streptokinase: 17, heparin: 24) diagnosed with PE (massive: 33 [32.04%], submassive: 50 [48.54%], and minor: 20 [19.42%]) were included.Results: Mean age was 50.04 years and major risk factors were immobilization due to hospitalization, history of deep vein thrombosis, and diabetes. Common clinical symptoms of dyspnoea, right ventricular dysfunction, and cough were found in 94.17%, 81.55%, and 77.67% patients, respectively. Between treatment and day 7, death occurred in 4.84%, 5.88%, and 8.33% patients in the tenecteplase, streptokinase, and heparin groups, respectively. The differences among treatment groups were non-significant (p > .05). All treatments have demonstrated significant alleviation of dyspnoea and heart rate (p < .05). Significant (p < .05) increase in oxygen saturation was seen and it was markedly higher in the tenecteplase-treated patients compared with the streptokinase- and heparin-treated patients. By day 7, there was 100% resolution of right bundle branch block only in the tenecteplase group. No intracranial bleeding or fatal bleeding episodes were found in any group.Conclusion: Tenecteplase was found to be effective in patients with PE irrespective of their clinical status and no major adverse events were noted.

Efficacy and safety of tenecteplase in pulmonary embolism

Pulmonary embolism (PE) is a relatively common life-threatening cardiovascular condition associated with significant morbidity and mortality. We present the efficacy and safety data of weight-adjusted tenecteplase in 30 consecutive patients of acute PE. 30 patients (22 male, 8 female) with acute PE were included in the study and divided into three groups: (1) Acute PE complicated by shock stage and/or persistent hypotension (12 patients). (2) RV dilatation and/or dysfunction without hypotension (14 patients). (3) Severe hypoxemia without hypotension and RV dysfunction (4 patients). Predominant symptoms were dyspnoea, cough, chest pain, syncope and haemoptysis, noted in 100% (30), 40% (12), 54% (16), 32% (9) and 10% (3) of patients respectively. RV dilatation and dyskinesia were present in 86%, septal paradoxical movement in 73% and inferior venacava collapse absent in 53% of patients respectively. 12 patients presented with acute PE and cardiogenic shock, 14 patients showed RV dilatation and dysfunction with systolic BP >90 mmHg and four patients were having RV dilation without dysfunction but severe hypoxemia. There was significant reduction in right ventricular systolic pressure and improvement in right ventricular dysfunction. Our study shows that tenecteplase is very effective and safe in the treatment of PE with minimal risk of bleeding in high risk group and intermediate risk and even in selective low risk category group of patients. However, in view of small number of patients in study group, a large multicentre randomized study would be required to draw a firm conclusion regarding the thrombolysis in low risk category patient.

Intraluminal Thrombus in Facilitated Versus Primary Percutaneous Coronary Intervention: An Angiographic Substudy of the ASSENT-4 PCI (Assessment of the Safety and Efficacy of a New Treatment Strategy With Percutaneous Coronary Intervention) Trial

This study investigated the occurrence of intraluminal thrombus and its potential implications with facilitated percutaneous coronary interventions (fPCIs). The effect of fPCI on the presence and consequences of intraluminal thrombus is unknown. Thrombolysis In Myocardial Infarction (TIMI) flow grade, frame count, and thrombus grade; distal embolization; and slow flow in the infarct-related artery were assessed in a blinded fashion on coronary angiograms in 1,342 patients from the ASSENT-4 PCI (Assessment of the Safety and Efficacy of a New Treatment Strategy With Percutaneous Coronary Intervention) trial. Residual TIMI thrombus grade ≥2 and/or distal embolization and/or slow flow, reflecting thrombus burden (TB), following PCI were correlated with ST-segment resolution, epicardial blood flow, and clinical outcome. The clinical composite endpoint was death, congestive heart failure, or shock. In the fPCI group, more TIMI flow grade 2/3 in the infarct-related artery at the first angiogram (73.7% vs. 33.4%, p < 0.001) and a higher TB following PCI (19.7% vs. 13.4%, p = 0.002) were found in comparison with the primary PCI group. Post-PCI TIMI thrombus grade was significantly associated with ST-segment resolution (p < 0.001) and TIMI frame count (p < 0.0001) in both groups. In the fPCI group, the presence of post-PCI thrombus was associated with a significantly worse outcome at 90 days (clinical composite endpoint: 32.1% vs. 18.6%, p = 0.023). Multivariable logistic regression showed that facilitation with tenecteplase (p = 0.005) and TB (odds ratio: 2.43, 95% confidence interval: 1.30 to 4.51, p = 0.0052) were independent predictors of 90-day mortality. In ASSENT-4 PCI, despite more patency, residual TB was significantly higher in fPCI patients and was associated with less efficient tissue reperfusion and worse clinical outcomes. (A Trial Evaluating the Efficacy and Safety of Tenecteplase Together With Unfractionated Heparin Prior to Early Percutaneous Coronary Intervention [PCI] as Compared to Standard Primary PCI in Patients With Acute Myocardial Infarction [ASSENT-4 PCI]; NCT00168792).

Risks and Benefits of Antiplatelet Therapy in Uremic Patients

Patients with renal insufficiency are at an increased risk for cardiovascular morbidity and mortality. Despite being at a substantial risk for thrombotic events, patients with renal insufficiency also experience a greater number of hemorrhagic complications associated with antiplatelet therapy than individuals with normal renal function. This review focuses on the benefits and risks of antiplatelet therapy in patients with impaired kidney function suffering from an acute coronary syndrome.

Tenecteplase in the Treatment of Thrombosed Hemodialysis Grafts

A pilot study was carried out to prospectively evaluate the efficacy and safety of Tenecteplase (TNKase) using a modified 'lyse and wait" technique with percutaneous transluminal angioplasty (PTA) to treat thrombosed hemodialysis arteriovenous grafts (AVG)s. Seven patients with eight hemodialysis AVGs were treated and followed up to 1 year. Dosing included 1 mg TNKase and 3,000-4,000 U of heparin. Technical and clinical success rates were 100% and 88%, respectively. No major complications occurred. Primary patency rates at 30, 90, and 180 days were 62%, 50%, and 33%, respectively. TNKase, used in this fashion, may be comparable to alteplase and reteplase for safe and effective thrombolysis of PTFE dialysis grafts.

International multicentre trial protocol to assess the efficacy and safety of tenecteplase during cardiopulmonary resuscitation in patients with out‐of‐hospital cardiac arrest: The Thrombolysis in Cardiac Arrest (TROICA) Study

Prehospital cardiac arrest has been associated with a very poor prognosis. Acute myocardial infarction and massive pulmonary embolism are the underlying causes of out-of-hospital cardiac arrest in 50-70% of patients. Although fibrinolysis is an effective treatment strategy for both myocardial infarction and pulmonary embolism, clinical experience for this therapy performed during resuscitation has been limited owing to the anticipated risk of severe bleeding complications. The TROICA study is planned as one of the largest randomized, double-blind, placebo-controlled trials to assess the efficacy and safety of prehospital thrombolytic therapy in cardiac arrest of presumed cardiac origin. Approximately 1000 patients with cardiac arrest will be randomized at approximately 60 international study centres to receive either a weight-adjusted dose of tenecteplase or placebo after the first dose of a vasopressor. Patients can be included if they are at least 18 years, presenting with a witnessed cardiac arrest of presumed cardiac origin, and if either basic life support had started within 10 min of onset and had been performed up to 10 min or advanced life support is started within 10 min of onset of cardiac arrest. Primary endpoint of the study is the 30-day survival rate, and the coprimary endpoint is hospital admission. Secondary endpoints are the return of spontaneous circulation (ROSC), survival after 24 h, survival to hospital discharge, and neurological performance. Safety endpoints include major bleeding complications and symptomatic intracranial haemorrhage.

Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting: the assessment of the safety and efficacy of a new thrombolytic regimen (ASSENT) 3 plus randomized trial in acute myocardial infarction

The use of tranexamic acid (TXA) in the treatment of trauma patients was relatively unexplored until the landmark Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage-2 (CRASH-2) trial in 2010 demonstrated a reduction in mortality with the use of TXA. Although this trial was a randomized, double-blinded, placebo-controlled study incorporating >20,000 patients, numerous limitations and weaknesses have been described. As a result, additional studies have followed, delineating the potential risks and benefits of TXA administration. A systematic review of the literature to date reveals a mortality benefit of early (ideally <1 hour and no later than 3 hours after injury) TXA administration in the treatment of severely injured trauma patients (systolic blood pressure <90 mm Hg, heart rate >110). Combined with abundant literature showing a reduction in bleeding in elective surgery, the most significant benefit may be administration of TXA before the patient goes into shock. Those trials that failed to show a mortality benefit of TXA in the treatment of hemorrhagic shock acknowledged that most patients received blood products before TXA administration, thus confounding the results. Although the use of prehospital TXA in the severely injured trauma patient will become more clear with the trauma studies currently underway, the current literature supports the use of prehospital TXA in this high-risk population. We recommend considering a 1 g TXA bolus en route to definitive care in high-risk patients and withholding subsequent doses until hyperfibrinolysis is confirmed by thromboelastography.

The assessment of the safety and efficacy of a new thrombolytic regimen (assent)-3 investigators. efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the assent-3 randomized trial in acute myocardial infarction

The assessment of the safety and efficacy of a new thrombolytic regimen (assent)-3 investigators. efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the assent-3 randomized trial in acute myocardial infarction