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Indian Heart Journal 2014
Topics: Female; Fibrinolytic Agents; Humans; Male; Myocardial Infarction; Tissue Plasminogen Activator
PubMed: 24814131
DOI: 10.1016/j.ihj.2014.02.013 -
Stroke Dec 2015We compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
We compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage.
METHODS
Venous blood samples from a subgroup of participants in the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, d-dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann-Whitney tests for between-group differences.
RESULTS
Thirty patients were included (alteplase=14 and tenecteplase=16) with similar baseline demographics. Compared with baseline, alteplase caused significant hypofibrinogenaemia (P=0.002), prolonged prothrombin time (P=0.011), hypoplasminogenaemia (P=0.001), and lower factor V (P=0.002) at 3 to 12 hours after administration with persistent hypofibrinogenaemia at 24 hours (P=0.011), whereas only minor hypoplasminogenaemia (P=0.029) was seen in the tenecteplase group. Tenecteplase consumed less plasminogen (P<0.001) and fibrinogen (P=0.002) compared with alteplase.
CONCLUSIONS
In patients with acute ischemic stroke, alteplase 0.9 mg/kg caused significant disruption of the fibrinolytic system, whereas tenecteplase 0.25 mg/kg did not, consistent with the trend toward lower intracerebral hemorrhage incidence with tenecteplase in the ATTEST study.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472926.
Topics: Aged; Aged, 80 and over; Blood Coagulation; Brain Ischemia; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Stroke; Tenecteplase; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 26514192
DOI: 10.1161/STROKEAHA.115.011290 -
BMJ Open Sep 2022Endovascular therapy (EVT) has proven to be clinically effective in treating large vessel occlusion acute ischaemic stroke (AIS), either alone or in combination with...
OBJECTIVES
Endovascular therapy (EVT) has proven to be clinically effective in treating large vessel occlusion acute ischaemic stroke (AIS), either alone or in combination with intravenous alteplase. Despite this, there is a limited evidence on the cost-effectiveness of EVT in Thailand and other low-income and middle-income countries. This study aims to assess whether EVT is a cost-effective therapy for AIS, and to estimate the fiscal burden to the Thai government through budget impact analysis.
METHODS
An economic evaluation was performed to compare AIS therapy with and without EVT from a societal perspective. The primary outcome was incremental cost-effectiveness per quality-adjusted life year (QALY) gained. Clinical parameters were derived from both national and international literature, while cost and utility data were collected locally. The analysis applied a cost-effectiveness threshold of 160 000 Baht (~$5000) per QALY, as set by the Thai government.
RESULTS
Both EVT alone and EVT combined with intravenous alteplase, among patients who are ineligible and eligible for intravenous alteplase, respectively, improved health outcomes but incurred additional cost. The combination of EVT and intravenous alteplase was associated with an incremental cost-effectiveness ratio (ICER) of 146 800 THB per QALY gained compared with intravenous alteplase alone, and the ICER of EVT alone compared with supportive care among patients ineligible for intravenous alteplase was estimated at 115 000 THB per QALY gained. Sensitivity analysis showed that the price of EVT has the greatest impact on model outcomes. Over a time horizon of 5 years, the introduction of EVT into the Thai health benefit package would require an additional budget of 887 million THB, assuming 2000 new cases per year.
CONCLUSIONS
EVT represents good value for money in the Thai context, both when provided to patients eligible for intravenous alteplase, and when provided alone to those who are ineligible for intravenous alteplase.
Topics: Brain Ischemia; Cost-Benefit Analysis; Humans; Ischemic Stroke; Quality-Adjusted Life Years; Stroke; Thailand; Tissue Plasminogen Activator
PubMed: 36167373
DOI: 10.1136/bmjopen-2022-064403 -
Vascular Health and Risk Management 2009After publication of the results of the National Institute of Neurological Disorders and Stroke study, the application of intravenous thrombolysis for ischemic stroke... (Review)
Review
After publication of the results of the National Institute of Neurological Disorders and Stroke study, the application of intravenous thrombolysis for ischemic stroke was launched and has now been in use for more than 10 years. The approval of this drug represented only the first step of the therapeutic approach to this pathology. Despite proven efficacy, concerns remain regarding the safety of recombinant tissue-type plasminogen activator for acute ischemic stroke used in routine clinical practice. As a result, a small proportion of patients are currently treated with thrombolytic drugs. Several factors explain this situation: a limited therapeutic window, insufficient public knowledge of the warning signs for stroke, the small number of centers able to administer thrombolysis on a 24-hour basis and an excessive fear of hemorrhagic complications. The aim of this review is to explore the clinical efficacy of treatment with alteplase and consider the hemorrhagic risks.
Topics: Brain Ischemia; Drug Administration Schedule; Fibrinolytic Agents; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Intracranial Hemorrhages; Recombinant Proteins; Risk Assessment; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 19475777
DOI: 10.2147/vhrm.s4561 -
European Stroke Journal Sep 2023Alteplase is widely used as an intravenous thrombolytic drug in acute ischemic stroke (AIS). Recently however, tenecteplase, a modified form of tissue plasminogen...
INTRODUCTION
Alteplase is widely used as an intravenous thrombolytic drug in acute ischemic stroke (AIS). Recently however, tenecteplase, a modified form of tissue plasminogen activator, has been shown to increase early recanalization rate and has proven to be non-inferior with a similar safety profile compared to alteplase. This study aims to evaluate the cost-effectiveness of 0.25 mg/kg tenecteplase versus 0.9 mg/kg alteplase for intravenous thrombolysis in AIS patients from the Dutch healthcare payer perspective.
METHODS
A Markov decision-analytic model was constructed to assess total costs, total quality-adjusted life year (QALY), an incremental cost-effectiveness ratio, and incremental net monetary benefit (INMB) of two treatments at willingness-to-pay (WTP) thresholds of €50,000/QALY and €80,000/QALY over a 10-year time horizon. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were conducted to test the robustness of results. Clinical data were obtained from large randomized controlled trials and real-world data.
RESULTS
Treatment with tenecteplase saved €21 per patient while gaining 0.05 QALYs, resulting in INMB of €2381, clearly rendering tenecteplase cost-effective compared to alteplase. Importantly, tenecteplase remained the cost-effective alternative in all scenarios, including AIS patients due to large vessel occlusion (LVO). Probabilistic sensitivity analysis proved tenecteplase to be cost-effective with a 71.0% probability at a WTP threshold of €50,000/QALY.
CONCLUSIONS
Tenecteplase treatment was cost-effective for all AIS patients (including AIS patients with LVO) compared to alteplase. The finding supports the broader use of tenecteplase in acute stroke care, as health outcomes improve at acceptable costs while having practical advantages, and a similar safety profile.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Cost-Benefit Analysis; Ischemic Stroke; Stroke
PubMed: 37641549
DOI: 10.1177/23969873231174943 -
The Journal of International Medical... Apr 2019To investigate the role of alteplase, a widely-used thrombolytic drug, in platelet function.
OBJECTIVE
To investigate the role of alteplase, a widely-used thrombolytic drug, in platelet function.
METHODS
Human platelets were incubated with different concentrations of alteplase followed by analysis of platelet aggregation in response to adenosine diphosphate (ADP), collagen, ristocetin, arachidonic acid or epinephrine using light transmittance aggregometry. Platelet activation and surface levels of platelet receptors GPIbα, GPVI and αIIbβ3 were analysed using flow cytometry. The effect of alteplase on clot retraction was also examined.
RESULTS
This study demonstrated that alteplase significantly inhibited platelet aggregation in response to ADP, collagen and epinephrine in a dose-dependent manner, but it did not affect ristocetin- or arachidonic acid-induced platelet aggregation. Alteplase did not affect platelet activation as demonstrated by no differences in P-selectin levels and PAC-1 binding being observed in collagen-stimulated platelets after alteplase treatment compared with vehicle. There were no changes in the surface levels of the platelet receptors GPIbα, GPVI and αIIbβ3 in alteplase-treated platelets. Alteplase treatment reduced thrombin-mediated clot retraction.
CONCLUSIONS
Alteplase inhibits platelet aggregation and clot retraction without affecting platelet activation and surface receptor levels.
Topics: Blood Coagulation; Blood Platelets; Humans; Platelet Activation; Platelet Aggregation; Platelet Function Tests; Platelet Glycoprotein GPIIb-IIIa Complex; Platelet Glycoprotein GPIb-IX Complex; Platelet Membrane Glycoproteins; Tissue Plasminogen Activator
PubMed: 30799665
DOI: 10.1177/0300060519829991 -
Stroke Mar 2021In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand... (Observational Study)
Observational Study
BACKGROUND AND PURPOSE
In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand changed to routine off-label intravenous tenecteplase due to improved early recanalization in large vessel occlusion, inconsistent access to thrombectomy within stroke networks, and for consistency in treatment protocols between patients with and without large vessel occlusion. We report the feasibility and safety outcomes in tenecteplase-treated patients.
METHODS
We performed a retrospective analysis of consecutive patients thrombolyzed with intravenous tenecteplase at 1 comprehensive and 2 regional stroke centers from July 14, 2018, to February 29, 2020. We report the baseline clinical characteristics, rates of symptomatic intracranial hemorrhage, and angioedema. These were then compared with patient outcomes with those treated with intravenous alteplase at 2 other comprehensive stroke centers. Multivariable mixed-effects logistic regression models were performed assessing the association of tenecteplase with symptomatic intracranial hemorrhage and independent outcome (modified Rankin Scale score, 0-2) at day 90.
RESULTS
There were 165 patients treated with tenecteplase and 254 with alteplase. Age (75 versus 74 years), sex (56% versus 60% male), National Institutes of Health Stroke Scale scores (8 versus 10), median door-to-needle times (47 versus 48 minutes), or onset-to-needle time (129 versus 130 minutes) were similar between the groups. Symptomatic intracranial hemorrhage occurred in 3 (1.8% [95% CI, 0.4-5.3]) tenecteplase patients compared with 7 (2.7% [95% CI, 1.1-5.7]) alteplase patients (=0.75). There were no differences between tenecteplase and alteplase in the rates of angioedema (4 [2.4%; 95% CI, 0.7-6.2] versus 1 [0.4%; 95% CI, 0.01-2.2], =0.08) or 90-day functional independence (100 [61%] versus 140 [57%], =0.47), respectively. In mixed-effects logistic regression models, there was no significant association between thrombolytic choice and symptomatic intracranial hemorrhage (odds ratio tenecteplase, 0.62 [95% CI, 0.14-2.80], =0.53) or functional independence (odds ratio tenecteplase, 1.20 [95% CI, 0.74-1.95], =0.46).
CONCLUSIONS
Routine use of tenecteplase for stroke thrombolysis was feasible and had comparable safety profile and outcome to alteplase.
Topics: Administration, Intravenous; Aged; Aged, 80 and over; Angioedema; Feasibility Studies; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Ischemic Stroke; Male; Middle Aged; Retrospective Studies; Tenecteplase; Thrombolytic Therapy; Time-to-Treatment; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 33588597
DOI: 10.1161/STROKEAHA.120.030859 -
European Stroke Journal Dec 2023The New Zealand (NZ) Central Region Stroke Network, serving 1.17 million catchment population, changed to tenecteplase for stroke thrombolysis in 2020 but was forced to...
INTRODUCTION
The New Zealand (NZ) Central Region Stroke Network, serving 1.17 million catchment population, changed to tenecteplase for stroke thrombolysis in 2020 but was forced to revert to Alteplase in 2021 due to a sudden cessation of drug supply. We used this unique opportunity to assess for potential before and after temporal trend confounding.
PATIENTS AND METHODS
In NZ all reperfused patients are entered prospectively into a national database for safety monitoring. We assessed Central Region patient outcomes and treatment metrics over three time periods: alteplase use (January 2018-January 2020); during switch to tenecteplase (February 2020-February 2021) and after reverting to alteplase (February 2021-December 2022) adjusting regression analyses for hospital, age, onset-to-needle, NIHSS, pre-morbid mRS and thrombectomy.
RESULTS
Between January 2018 and December 2022, we treated 1121 patients with Alteplase and 286 with tenecteplase. Overall, patients treated with tenecteplase had greater odds of favorable outcome ordinal mRS [aOR = 1.43 (95% CI = 1.11-1.85)]; shorter door-to-needle (DTN) time [median 52 (IQR 47-83) vs 61 (45-84) minutes, < 0.0001] and needle to groin (NTG) times [118 (74.5-218.5) vs 185 (118-255); = 0.02)]. Symptomatic intracerebral hemorrhage (sICH) rate was lower in tenecteplase group [aOR 0.29 (0.09-0.95)]. Findings similarly favored tenecteplase when comparing tenecteplase to only the second alteplase phase. There was no inter-group difference when comparing the two alteplase phases.
CONCLUSIONS
Our results suggest that previously reported benefits from tenecteplase in a real-world setting were not likely attributable to a temporal confounding.
Topics: Humans; Tenecteplase; Tissue Plasminogen Activator; Fibrinolytic Agents; Brain Ischemia; Stroke
PubMed: 37489615
DOI: 10.1177/23969873231187436 -
Journal of Neurointerventional Surgery Jul 2022Randomized trials have not demonstrated benefit from intravenous thrombolysis among patients undergoing endovascular thrombectomy (EVT). However, these trials included...
BACKGROUND
Randomized trials have not demonstrated benefit from intravenous thrombolysis among patients undergoing endovascular thrombectomy (EVT). However, these trials included primarily patients presenting directly to an EVT capable hub center. We sought to study outcomes for EVT candidates who presented to spoke hospitals and were subsequently transferred for EVT consideration, comparing those administered alteplase at spokes (i.e., 'drip-and-ship' model) versus those not.
METHODS
Consecutive EVT candidates presenting to 25 spokes from 2018 to 2020 with pre-transfer CT angiography defined emergent large vessel occlusion and Alberta Stroke Program CT score ≥6 were identified from a prospectively maintained Telestroke database. Outcomes of interest included adequate reperfusion (Thrombolysis in Cerebral Infarction (TICI) 2b-3), intracerebral hemorrhage (ICH), discharge functional independence (modified Rankin Scale (mRS) ≤2), and 90 day functional independence.
RESULTS
Among 258 patients, median age was 70 years (IQR 60-81), median National Institutes of Health Stroke Scale (NIHSS) score was 13 (6-19), and 50% were women. Ninety-eight (38%) were treated with alteplase at spokes and 113 (44%) underwent EVT at the hub. Spoke alteplase use independently increased the odds of discharge mRS ≤2 (adjusted OR 2.43, 95% CI 1.08 to 5.46, p=0.03) and 90 day mRS ≤2 (adjusted OR 3.45, 95% CI 1.65 to 7.22, p=0.001), even when controlling for last known well, NIHSS, and EVT; it was not associated with an increased risk of ICH (OR 1.04, 95% CI 0.39 to 2.78, p=0.94), and there was a trend toward association with greater TICI 2b-3 (OR 3.59, 95% CI 0.94 to 13.70, p=0.06).
CONCLUSIONS
Intravenous alteplase at spoke hospitals may improve discharge and 90 day mRS and should not be withheld from EVT eligible patients who first present at alteplase capable spoke hospitals that do not perform EVT. Additional studies are warranted to confirm and further explore these benefits.
Topics: Aged; Aged, 80 and over; Brain Ischemia; Cerebral Hemorrhage; Endovascular Procedures; Female; Humans; Male; Middle Aged; Reperfusion; Retrospective Studies; Stroke; Thrombectomy; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 34326197
DOI: 10.1136/neurintsurg-2021-017819 -
Is tenecteplase ready to replace alteplase to treat acute ischaemic stroke? The knowns and unknowns.Stroke and Vascular Neurology Feb 2022
Topics: Brain Ischemia; Humans; Ischemic Stroke; Stroke; Tenecteplase; Tissue Plasminogen Activator
PubMed: 34667106
DOI: 10.1136/svn-2021-001321