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Stem Cell Research & Therapy Jun 2018Neural stem cells (NSCs) play vital roles in brain homeostasis and exhibit a broad repertoire of potentially therapeutic actions following neurovascular injury. One such... (Review)
Review
Neural stem cells (NSCs) play vital roles in brain homeostasis and exhibit a broad repertoire of potentially therapeutic actions following neurovascular injury. One such injury is stroke, a worldwide leading cause of death and disability. Clinically, extensive injury from ischemic stroke results from ischemia-reperfusion (IR), which is accompanied by inflammation, blood-brain barrier (BBB) damage, neural cell death, and extensive tissue loss. Tissue plasminogen activator (tPA) is still the only US Food and Drug Administration-approved clot-lysing agent. Whereas the thrombolytic role of tPA within the vasculature is beneficial, the effects of tPA (in a non-thrombolytic role) within the brain parenchyma have been reported as harmful. Thus, new therapies are needed to reduce the deleterious side effects of tPA and quickly facilitate vascular repair following stroke. The Stroke Treatment Academic Industry Roundtable (STAIR) recommends that stroke therapies "focus on drugs/devices/treatments with multiple mechanisms of action and that target multiple pathways". Thus, based on multifactorial ischemic cascades in various stroke stages, effective stroke therapies need to focus on targeting and ameliorating early IR injury as well as facilitating angiogenesis, neurogenesis, and neurorestorative mechanisms following stroke. This review will discuss the preclinical perspectives of NSC transplantation as a promising treatment for neurovascular injury and will emphasize both the subacute and chronic phase of ischemic stroke.
Topics: Brain Ischemia; Chronic Disease; Humans; Stem Cell Transplantation; Stroke; Tissue Plasminogen Activator
PubMed: 29895321
DOI: 10.1186/s13287-018-0913-2 -
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 -
Med (New York, N.Y.) Aug 2022The standard medical therapy for intravenous thrombolysis in patients with stroke presenting within 3 h is alteplase, a tissue plasminogen activator. Menon and...
The standard medical therapy for intravenous thrombolysis in patients with stroke presenting within 3 h 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 4.5 h of onset.
Topics: Brain Ischemia; Fibrinolytic Agents; Humans; Ischemic Stroke; Tenecteplase; Tissue Plasminogen Activator
PubMed: 35963230
DOI: 10.1016/j.medj.2022.07.006 -
International Journal of Stroke :... Oct 2020Intraventricular hemorrhage occurs due to intracerebral hemorrhage with intraventricular extension or without apparent parenchymal involvement, known as primary...
BACKGROUND
Intraventricular hemorrhage occurs due to intracerebral hemorrhage with intraventricular extension or without apparent parenchymal involvement, known as primary intraventricular hemorrhage.
AIMS
We evaluated the prognosis of primary intraventricular hemorrhage patients in the CLEAR III trial (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage).
METHODS
In patients with primary intraventricular hemorrhage versus those with secondary intraventricular hemorrhage, we compared intraventricular alteplase response and outcomes including modified Rankin Scale, Barthel Index, National Institutes of Health Stroke Scale (NIHSS), and extended Glasgow Outcome Scale (eGOS) at 30, 180, and 365 days. Outcomes were also compared in primary intraventricular hemorrhage patients who received intraventricular alteplase versus placebo (normal saline) and in matched primary and secondary intraventricular hemorrhage patients using inverse-probability-weighted regression adjustment.
RESULTS
Of 500 patients enrolled in CLEAR III, 46 (9.2%) had primary intraventricular hemorrhage. Combining both treatment groups, primary intraventricular hemorrhage patients had larger intraventricular hemorrhage volumes (median: 34.2 mL vs. 20.8 mL, < 0.01) but similar intraventricular hemorrhage removal (51.0% vs. 59.0%, = 0.24) compared to secondary intraventricular hemorrhage patients, respectively. Confirming previous studies, primary intraventricular hemorrhage patients achieved better NIHSS, modified Rankin Scale, Barthel Index, and eGOS scores at days 30, 180, and 365, respectively (all < 0.01), although mortality was similar to secondary intraventricular hemorrhage patients; matching analysis yielded similar results. Primary intraventricular hemorrhage patients who received intraventricular alteplase ( = 19) and saline ( = 27) achieved similar outcomes.
CONCLUSIONS
In CLEAR III, primary intraventricular hemorrhage patients who survived achieved better long-term outcomes than surviving secondary intraventricular hemorrhage patients with similar mortality. Outcomes and safety were similar between primary intraventricular hemorrhage patients receiving alteplase and those receiving saline.
Topics: Cerebral Hemorrhage; Fibrinolytic Agents; Humans; Stroke; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 32075571
DOI: 10.1177/1747493020908146 -
Scientific Reports Oct 2018Uric acid (UA) therapy may prevent early ischemic worsening after acute stroke in thrombolysis patients. The aim of this study was to examine the influence of UA on the...
Uric acid (UA) therapy may prevent early ischemic worsening after acute stroke in thrombolysis patients. The aim of this study was to examine the influence of UA on the thrombolytic efficacy of alteplase in human blood samples by measuring thrombolysis under flow conditions using a newly developed microchip-based flow-chamber assay. Human blood samples from healthy volunteers were exposed to UA, alteplase, or a combination of UA and alteplase. Whole blood and platelet-rich plasma were perfused over a collagen- and thromboplastin-coated microchip, and capillary occlusion was monitored with a video microscope and flow-pressure sensor. The area under the curve (extent of thrombogenesis or thrombolysis) at 30 minutes was 92% lower in the UA-alteplase-treated group compared with the alteplase-treated group. D-dimers were measured to evaluate these effects in human platelet-poor plasma samples. Although hydrogen peroxide significantly decreased the elevation of D-dimers by alteplase, UA significantly inhibited the effect of hydrogen peroxide. Meanwhile, rat models of thromboembolic cerebral ischemia were treated with either alteplase or UA-alteplase combination therapy. Compared with alteplase alone, the combination therapy reduced the infarct volume and inhibited haemorrhagic transformation. UA enhances alteplase-mediated thrombolysis, potentially by preventing oxidative stress, which inhibits fibrinolysis by alteplase in thrombi.
Topics: Adult; Animals; Antioxidants; Area Under Curve; Disease Models, Animal; Endothelial Cells; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Ischemia; Male; Microscopy, Video; Oxidative Stress; ROC Curve; Rats; Rats, Sprague-Dawley; Tissue Plasminogen Activator; Uric Acid; Young Adult
PubMed: 30367108
DOI: 10.1038/s41598-018-34220-1 -
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 Thrombosis and Haemostasis :... Jul 2011The first generation of clinical reperfusion treatment, intravenous (IV) fibrinolysis with tissue plasminogen activator (tPA), was a transformative breakthrough in... (Review)
Review
BACKGROUND
The first generation of clinical reperfusion treatment, intravenous (IV) fibrinolysis with tissue plasminogen activator (tPA), was a transformative breakthrough in stroke care, but is far from ideal.
OBJECTIVES
TO survey emerging strategies to increase the efficacy and safety of cerebral reperfusion therapy.
METHODS
Narrative review.
RESULTS AND CONCLUSIONS
Innovative IV pharmacologic reperfusion strategies include: extending IV tPA use to patients with mild deficits; developing novel fibrinolytic agents (tenecteplase, desmetolplase, plasmin); using ultrasound to enhance enzymatic fibrinolysis; combination clot lysis therapies (fibrinolytics with GPIIb/IIIa agents or direct thrombin inhibitors); co-administration of MMP-9 inhibitors to deter haemorrhagic transformation; and prehospital neuroprotection to support threatened tissues until reperfusion. Endovascular recanalisation strategies are rapidly evolving, and include intra-arterial fibrinolysis, mechanical clot retrieval, suction thrombectomy, and primary stenting. Combined approaches appear especially promising, using IV fibrinolysis to rapidly initiate reperfusion, mechanical endovascular treatment to debulk large, proximal thrombi, and intra-arterial (IA) fibrinolysis to clear residual distal thrombus elements and emboli.
Topics: Acute Disease; Brain Ischemia; Fibrinolysis; Humans; Infusions, Intravenous; Stroke; Tissue Plasminogen Activator
PubMed: 21781270
DOI: 10.1111/j.1538-7836.2011.04371.x -
BMC Pulmonary Medicine Nov 2022Intrapleural fibrinolytic therapy (IPFT) is one of the treatment options for complex pleural effusion. In this study, the IPFT agent used was alteplase, a tissue... (Comparative Study)
Comparative Study
BACKGROUND
Intrapleural fibrinolytic therapy (IPFT) is one of the treatment options for complex pleural effusion. In this study, the IPFT agent used was alteplase, a tissue plasminogen activator (t-PA). This study aims to determine the difference in the outcome of patients with complex pleural effusion between IPFT and surgery in terms of radiological improvement, inflammatory parameters, length of stay, and post-intervention complications.
METHODS
A retrospective review of patients with complex pleural effusion treated at Universiti Kebangsaan Malaysia Medical Center from January 2012 to August 2020 was performed. Patient demographics, chest imaging, drainage chart, inflammatory parameters, length of hospital stay, and post-intervention and outcome were analyzed.
RESULTS
Fifty-eight patients were identified (surgical intervention, n = 18; 31% and IPFT, n = 40, 69%). The mean age was 51.7 ± 18.2 years. Indication for surgical intervention was pleural infection (n = 18; 100%), and MPE (n = 0). Indications for IPFT was pleural infection (n = 30; 75%) and MPE (n = 10; 25%). The dosages of t-PA were one to five doses of 2-50 mg. The baseline chest radiograph in the IPFT group was worse than in the surgical intervention group. (119.96 ± 56.05 vs. 78.19 ± 55.6; p = 0.029) At week 1, the radiological success rate for IPFT and surgical intervention were 27% and 20%, respectively, and at weeks 4-8, the success rate was 56% and 80% respectively. IPFT was associated with lesser complications; fever (17.5%), chest pain (10%), and non-life-threatening bleeding (5%).
CONCLUSION
IPFT was comparable to surgery in radiological outcome, inflammatory parameters, and length of stay with lesser reported complications.
Topics: Adult; Aged; Humans; Middle Aged; Fibrinolytic Agents; Pleural Diseases; Pleural Effusion; Retrospective Studies; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 36419155
DOI: 10.1186/s12890-022-02239-w -
Stroke and Vascular Neurology Jun 2017The characteristics of patients with acute ischaemic stroke (AIS) and their management vary across regions, which may influence outcomes. We examined for differential... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The characteristics of patients with acute ischaemic stroke (AIS) and their management vary across regions, which may influence outcomes. We examined for differential patterns of outcome between China and non-China participants of the ENhanced Control of Hypertension And Thrombolysis strokE stuDy (ENCHANTED), which tested different alteplase doses in AIS.
METHODS
ENCHANTED was an international, multicentre, open, blinded-endpoint trial of the effects of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase on 90-day disability outcomes and symptomatic intracerebral haemorrhage (sICH) in 3310 patients with AIS.
RESULTS
Participants (n=1419, 48%) in China were younger, and more often male, hypertensive and with prior stroke and coronary artery disease, but less likely to have atrial fibrillation and use antihypertensive, antithrombotic and lipid-lowering agents, compared with non-China patients with AIS. Although China participants had more AIS due to large artery occlusion, were treated later and had differing ancillary management, there was no significant difference in 90-day modified Rankin scale scores 2-6 (55.6% vs 47.8%; OR, adjusted for baseline and management factors 0.87 (95% CI 0.71 to 1.07; p=0.20)) and risk of sICH (Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria: 1.4% vs 1.8%; p=0.12) compared with non-China participants. There was no heterogeneity in the treatment effects of low-dose versus standard-dose alteplase between China and non-China participants.
CONCLUSION
Patients with AIS recruited to the ENCHANTED trial in China had similar outcomes in response to thrombolysis treatment despite significantly differing demographic, clinical and management factors to patients with AIS in other regions.
Topics: Aged; Aged, 80 and over; Cerebral Hemorrhage; China; Disability Evaluation; Female; Fibrinolytic Agents; Humans; Infusions, Intravenous; Ischemic Stroke; Male; Middle Aged; Prospective Studies; Recovery of Function; Risk Factors; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 28959492
DOI: 10.1136/svn-2017-000085 -
The American Journal of Managed Care Jul 2010To conduct a systematic literature review analyzing cost-effectiveness or cost savings associated with use of recombinant tissue plasminogen activator (rt-PA), stroke... (Review)
Review
OBJECTIVE
To conduct a systematic literature review analyzing cost-effectiveness or cost savings associated with use of recombinant tissue plasminogen activator (rt-PA), stroke centers, and telemedicine programs for acute ischemic stroke.
METHODS
A literature search was conducted of the PubMed/MEDLINE and Ovid/EMBASE databases from January 1, 1995, to August 30, 2008, limited to English-language articles and using the search terms [stroke and cost and telemedicine] or [stroke and cost and alteplase] or [stroke and cost and tissue plasminogen activator] or [stroke and cost and rt-PA] or [stroke center and cost] or [stroke unit and cost]. Abstracts were reviewed, and inclusion/exclusion criteria were used to select studies. The analysis was limited to studies addressing costs or cost-effectiveness of the interventions in the United States.
RESULTS
This search identified 748 abstracts, of which 24 were included. Among these 24 studies were 2 cost-effectiveness, 8 cost-savings, and 4 cost-benefit analyses. All discussed some aspect of practice economics. The primary cost-effectiveness data available for rt-PA use demonstrated increased hospitalization costs but long-term cost savings due to decreased nursing home and rehabilitation costs. No cost-effectiveness studies for stroke centers or telemedicine programs were identified, although stroke centers have been shown to reduce hospital length of stay and both stroke centers and telemedicine programs have demonstrated increased rates of rt-PA administration within 3 hours of the onset of stroke symptoms.
CONCLUSION
More high-quality, current cost-effectiveness research for stroke centers, care networks, and telemedicine is needed to inform treatment decisions and resource utilization.
Topics: Costs and Cost Analysis; Humans; Recombinant Proteins; Stroke; Telemedicine; Tissue Plasminogen Activator
PubMed: 20645669
DOI: No ID Found