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Iranian Journal of Pharmaceutical... 2021Reperfusion therapies are recommended for patients with hemodynamic instability or high-risk acute pulmonary embolism (PE). Lower doses of tissue plasminogen activator... (Review)
Review
Efficacy and Safety of Different Dosage of Recombinant Tissue-type Plasminogen Activator (rt-PA) in the Treatment of Acute Pulmonary Embolism: A Systematic Review and Meta-analysis.
Reperfusion therapies are recommended for patients with hemodynamic instability or high-risk acute pulmonary embolism (PE). Lower doses of tissue plasminogen activator (rt-PA) could be considered to improve bleeding complications. The aim of this study was to evaluate the efficacy and safety of a reduced dose of rt-PA for the treatment of acute PE, compared with anticoagulation and standard dose. PubMed Central, Scopus, Web of Science and Embase were searched for all relevant randomized studies and prospective observational studies that compared reduced dose of rt-PA with anticoagulation alone or standard dose of rt-PA in patients with acute PE. The risk ratios (RR, with 95% CI) were calculated according to the value of I2. Outcomes were described as bleeding events, all-cause death, and recurrence of PE. Thirteen articles, including four observational studies (4223 patients) and nine RCTs (780 patients), were included. In comparing reduced dose of rt-PA with anticoagulant, a greater incidence of total bleeding events in low dose was showed (RR, 5.08 (95% CI, (1.39-18.6), I2 = 0.0%). In the standard dose rt-PA reduced dose, there was a greater incidence of total bleeding events in the standard dose of rt-PA, RR 1.48 (95% CI, (1.00-2.19), I2 = 0.0%) was shown. There were no statistical differences in recurrent PE or all-cause mortality. It concluded that in the absence of the benefit of a standard dose of rt-PA in comparison with dose reduction, a reduced dose of rt-PA showed a lower rate of total bleeding events and similar efficacy regarding mortality and PE recurrence rate.
PubMed: 34567173
DOI: 10.22037/ijpr.2021.114142.14688 -
Journal of Neurology Jul 2018Our objective was to review economic evaluations on stent-retriever thrombectomy (SRT) added/not added to intravenous (IV) tissue plasminogen activator (t-PA) in acute... (Review)
Review
BACKGROUND
Our objective was to review economic evaluations on stent-retriever thrombectomy (SRT) added/not added to intravenous (IV) tissue plasminogen activator (t-PA) in acute ischemic stroke (AIS) due to large-vessel occlusion (LVO).
METHODS
We conducted a systematic review using several electronic databases and searching for studies published from January 2009 to September 2017.
INCLUSION CRITERIA
any publication type reporting the incremental cost-effectiveness ratio of SRT in people with AIS secondary to LVO. Quality assessment was undertaken with the CHEERS and the Philips' checklists.
RESULTS
Eight original articles (four from North America/four from Europe) were included; of these, seven were model-based cost-effectiveness studies and one was a study conducted alongside a clinical trial. The perspective was the healthcare system in seven studies, and societal in one. The time horizon was lifetime (minimum 20 years) in all but two studies where it was 1 and 5 years. Overall, studies were rated of good quality (mean score 79%; range 70-90). Data sources, effectiveness outcomes and other input parameters were heterogeneous across studies. In three studies, SRT was dominant (less expensive and more effective). In five studies, SRT was more expensive and generated more quality-adjusted life years but had a high probability (79-100%) to be cost-effective at conventional thresholds.
CONCLUSION
This review shows that SRT added/not added to IV t-PA is likely to be cost-effective or even dominant, which is consistent with the opinion from several Health Technology Assessment bodies recommending SRT. However, our findings are supported by primary studies with substantial methodological heterogeneity.
Topics: Brain Ischemia; Cost-Benefit Analysis; Electronic Health Records; Humans; Stents; Stroke; Thrombectomy; Tissue Plasminogen Activator
PubMed: 29392462
DOI: 10.1007/s00415-018-8760-8 -
Cureus Dec 2020Stroke is a leading cause of death, disability, and dementia worldwide. Strokes can be divided into ischemic strokes and hemorrhagic strokes. At the moment, tissue... (Review)
Review
Stroke is a leading cause of death, disability, and dementia worldwide. Strokes can be divided into ischemic strokes and hemorrhagic strokes. At the moment, tissue plasminogen activator (tPA) is the only FDA-approved drug for ischemic stroke. Minocycline (MC) and Magnesium (Mg) are promising therapies for ischemic stroke, especially in the pre-hospital setting. These drugs are readily available, inexpensive, and generally safe. We decided to investigate these drugs' neuroprotective effects in treating ischemic stroke in the acute and chronic setting. We conducted a systematic review of the published literature on MC and Mg's functional outcome in ischemic stroke. This paper's methodology included only clinical trials published in the last 15 years, using PubMed as a database. The systematic review demonstrated that MC infusion in the pre-hospital and hospital setting improved functional outcomes and disability scores. Furthermore, MC also decreased matrix metalloproteinase 9 (MMP-9) levels. MC might have a more significant effect on men than women because different molecular pathways of cerebral ischemia seem to be involved between both genders. The systematic review showed that patients with ischemic stroke did not benefit from magnesium sulfate infusion in the pre-hospital and hospital setting. Nevertheless, patients with lacunar strokes and patients who supplemented their meals with potassium-magnesium salt in the diet had better functional outcomes. Future studies would need a more significant sample of participants and a better selection to increase the study's power and avoid selection bias, respectively. Further publications could benefit from subcategorizing strokes and investigating the gender role in stroke treatment. These directives could give a more robust conclusion regarding the neuroprotective effects of these drugs.
PubMed: 33520535
DOI: 10.7759/cureus.12339 -
Frontiers in Endocrinology 2023Intravenous recombinant tissue plasminogen activator (rtPA) thrombolysis is an effective treatment for acute ischemic stroke. Hyperglycemia is a major risk factor for... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Intravenous recombinant tissue plasminogen activator (rtPA) thrombolysis is an effective treatment for acute ischemic stroke. Hyperglycemia is a major risk factor for the occurrence, development, and prognosis of ischemic stroke. This meta-analysis purposefully estimates the association between hyperglycemia and poor prognosis in acute ischemic stroke patients receiving intravenous rtPA thrombolytic therapy.
MATERIALS AND METHODS
According to the predefined inclusion criteria, we searched PubMed, Web of Science, and Cochrane Library databases. The association of high blood glucose(>140mg/dl) with symptomatic intracranial hemorrhage (sICH), poor clinical outcome and mortality at 90 days post-rtPA thrombolysis was studied using both a common effects model and a random effects model. Odds ratios (ORs) were plotted on forest plots.
RESULTS
Of a total cohort of 2565 patients who received intravenous thrombolytic therapy, 721 had higher blood glucose. High glucose level significantly increased the odds of sICH (OR 1.80; 95% confidence interval(95%CI): 1.30- 2.50) and poor clinical outcome at 90 days (OR 1.82; 95%CI: 1.52-2.19), and all-cause mortality at 90 days (OR 2.51; 95%CI:1.65-3.82).
CONCLUSIONS
In our meta-analysis, high blood glucose was significantly associated with sICH, poor clinical outcome and higher mortality at 90 days.
Topics: Humans; Tissue Plasminogen Activator; Stroke; Blood Glucose; Ischemic Stroke; Brain Ischemia; Fibrinolytic Agents; Prognosis; Thrombolytic Therapy; Intracranial Hemorrhages; Hyperglycemia
PubMed: 37124754
DOI: 10.3389/fendo.2023.1120779 -
Journal of the Neurological Sciences Feb 2023Studies on tenecteplase have been yielding mixed results for several important outcomes at different doses, thus hampering objective guideline recommendations in acute... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies on tenecteplase have been yielding mixed results for several important outcomes at different doses, thus hampering objective guideline recommendations in acute ischemic stroke management. This meta-analysis stratifies doses in order to refine our interpretation of outcomes and quantify the benefits and harms of tenecteplase at different doses.
METHODS
PubMed/MEDLINE, the Cochrane Library, and reference lists of the included articles were systematically searched. Several efficacy and safety outcomes were pooled and reported as risk ratios (RRs) with 95% confidence intervals (CIs). Network meta-analysis was used to find the optimal dose of tenecteplase. Meta-regression was run to investigate the impact of baseline NIHSS scores on functional outcomes and mortality.
RESULTS
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. Meta-regression demonstrated superior tenecteplase efficacy with increasing stroke severity, however, the results were statistically nonsignificant.
CONCLUSIONS
Tenecteplase at 0.25 mg/kg dose 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.
Topics: Humans; Cerebral Hemorrhage; Fibrinolytic Agents; Ischemic Stroke; Network Meta-Analysis; Randomized Controlled Trials as Topic; Tenecteplase; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 36630803
DOI: 10.1016/j.jns.2022.120537 -
Neurocritical Care Jun 2022Cerebral autoregulation (CA) prevents brain injury by maintaining a relatively constant cerebral blood flow despite fluctuations in cerebral perfusion pressure. This... (Review)
Review
Cerebral autoregulation (CA) prevents brain injury by maintaining a relatively constant cerebral blood flow despite fluctuations in cerebral perfusion pressure. This process is disrupted consequent to various neurologic pathologic processes, which may result in worsening neurologic outcomes. Herein, we aim to highlight evidence describing CA changes and the impact of CA monitoring in patients with cerebrovascular disease, including ischemic stroke, intracerebral hemorrhage (ICH), and aneurysmal subarachnoid hemorrhage (aSAH). The study was preformed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. English language publications were identified through a systematic literature conducted in Ovid Medline, PubMed, and Embase databases. The search spanned the dates of each database's inception through January 2021. We selected case-control studies, cohort observational studies, and randomized clinical trials for adult patients (≥ 18 years) who were monitored with continuous metrics using transcranial Doppler, near-infrared spectroscopy, and intracranial pressure monitors. Of 2799 records screened, 48 studies met the inclusion criteria. There were 23 studies on ischemic stroke, 18 studies on aSAH, 5 studies on ICH, and 2 studies on systemic hypertension. CA impairment was reported after ischemic stroke but generally improved after tissue plasminogen activator administration and successful mechanical thrombectomy. Persistent impairment in CA was associated with hemorrhagic transformation, malignant cerebral edema, and need for hemicraniectomy. Studies that investigated large ICHs described bilateral CA impairment up to 12 days from the ictus, especially in the presence of small vessel disease. In aSAH, impairment of CA was associated with angiographic vasospasm, delayed cerebral ischemia, and poor functional outcomes at 6 months. This systematic review highlights the available evidence for CA disruption during cerebrovascular diseases and its possible association with long-term neurological outcome. CA may be disrupted even before acute stroke in patients with untreated chronic hypertension. Monitoring CA may help in establishing individualized management targets in patients with cerebrovascular disease.
Topics: Adult; Brain Ischemia; Cerebral Hemorrhage; Cerebrovascular Circulation; Homeostasis; Humans; Hypertension; Ischemic Stroke; Stroke; Subarachnoid Hemorrhage; Tissue Plasminogen Activator; Vasospasm, Intracranial
PubMed: 35378665
DOI: 10.1007/s12028-022-01484-5 -
Journal of Diabetes and Metabolic... Dec 2020The 4G5G polymorphism of Plasminogen activator inhibitor-1 (PAI-1) gene is reported to be associated with diabetes nephropathy and retinopathy (DNR) risk. However, the... (Review)
Review
BACKGROUND
The 4G5G polymorphism of Plasminogen activator inhibitor-1 (PAI-1) gene is reported to be associated with diabetes nephropathy and retinopathy (DNR) risk. However, the findings are conflicting. Herein, we conducted a case-control and meta-analysis study to explore the association of PAI-1 4G5G polymorphism with risk of DNR.
METHODS
We retrieved PubMed, EMBASE, Web of Knowledge, and CNKI databases and screened eligible studies up to August 15, 2020. The strength of associations was assessed by odd ratio (OR) and the corresponding 95% confidence interval (95% CI).
RESULTS
A total of 27 case-control studies including 16 studies with 1,825 cases case and 1,731 controls on DN and eleven studies with 1,397 cases and 1,545 controls on DR were selected. Pooled data showed that the PAI-1 4G5G polymorphism was significantly associated with DN (allele model: OR = 0.674, 95% CI 0.524-0.865, p = 0.002; homozygote model: OR = 0.536, 95% CI 0.351-0.817, p = 0.004; heterozygote model: OR = 0.621, 95% CI 0.427-0.903, p = 0.013; dominant model: OR = 0.575, 95% CI 0.399-0.831, p = 0.003; and recessive model: OR = 0.711, 95% CI 0.515-0.981, p = 0.038) and DR (homozygote model: OR = 0.770, 95% CI 0.621-0.955, p = 0.0.017) risk. Stratified analyses by ethnicity indicated that PAI-1 4G5G polymorphism was associated with DN and DR risk in Asians and Caucasians, respectively.
CONCLUSIONS
The present meta-analysis revealed that the PAI-1 4G5G polymorphism was associated with increased risk of DN and DR risk. However, well-designed large-scale clinical studies are required to further validate our results.
PubMed: 33520873
DOI: 10.1007/s40200-020-00675-1 -
CNS Drugs Aug 2015Concerns about the harms of intravenous alteplase (recombinant tissue plasminogen activator) continue to deter physicians from treating patients with acute ischemic... (Meta-Analysis)
Meta-Analysis Review
Intravenous Recombinant Tissue Plasminogen Activator Does Not Impact Mortality in Acute Ischemic Stroke at Any Time Point up to 6 Months: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.
BACKGROUND AND OBJECTIVE
Concerns about the harms of intravenous alteplase (recombinant tissue plasminogen activator) continue to deter physicians from treating patients with acute ischemic stroke with the only drug proven to positively impact outcomes and reduce disability. Recent literature indicates an increase in mortality with alteplase within 7 days, an effect that does not persist from 3 months onwards. The objective of this meta-analysis was to pool mortality estimates from randomized controlled clinical trials (RCTs) at 7 days, 30 days, 90 days, and 6 months after stroke onset.
METHODS
PubMed, Embase, Scopus, CENTRAL, and clinicaltrials.gov were searched through to April 2014, using "hedges" for tissue plasminogen activator, acute ischemic stroke, and placebo. Two independent authors abstracted data and assessed study quality. Data were pooled using Dersimonian and Laird's random effects model.
RESULTS
Eleven RCTs (n = 6905) were included in the final analysis. Two authors independently performed study selection and data abstraction. There was no publication bias and total variance attributable to heterogeneity was not significant (I(2) < 50%) at any time point. There was no difference in mortality between alteplase and placebo groups at any time point. Trials that randomized patients beyond 3 h (excluded patients within the 3-h window) did not drive the mortality difference seen at any time point. Exclusion sensitivity analysis revealed that exclusion of the NINDS trial rendered the 7-day difference significant towards increased mortality with alteplase. Quality adjustment did not alter the results.
CONCLUSION
Intravenous alteplase did not impact mortality in patients with acute ischemic stroke at any of the measured time points up to 6 months (i.e., there was no increase in the risk of death with alteplase). Therefore, intravenous alteplase should be given to all eligible patients with acute ischemic stroke to improve long-term neurologic outcomes. The effects of alteplase on early survival are more complex than previously understood.
Topics: Administration, Intravenous; Brain Ischemia; Fibrinolytic Agents; Humans; Randomized Controlled Trials as Topic; Stroke; Time Factors; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 26251162
DOI: 10.1007/s40263-015-0265-8 -
Environmental Research Dec 2022Ambient air pollution is one of the major global risk factors for cardiovascular health, and coagulation changes have been proposed to mediate this risk. Plasminogen... (Meta-Analysis)
Meta-Analysis Review
Ambient air pollution is one of the major global risk factors for cardiovascular health, and coagulation changes have been proposed to mediate this risk. Plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), soluble P-selectin (sP-selectin) and tissue plasminogen activator (t-PA) are major coagulation biomarkers. However, there has been no systematic meta-analysis to summarize associations of ambient air pollution with these coagulation biomarkers. To assess the overall associations between ambient particulate matter (PM, PM), ozone (O), nitrogen dioxide (NO), carbon monoxide (CO) and major coagulation biomarkers including PAI-1, vWF, sP-selectin and t-PA based on the existing epidemiological research. We performed a systematic literature search of publications reporting the associations of ambient air pollutants (PM, PM, O, NO and CO) with coagulation biomarkers (PAI-1, vWF, sP-selectin and t-PA) in PubMed, Web of Science, EMBASE, and Scopus databases as of April 5, 2022. Then, we performed a random-effect meta-analysis, which included 27 articles, and then identified the potential sources of heterogeneity. The pooled percent changes of coagulation biomarkers per 10 μg/m increase in short-term exposure to ambient PM were 2.43% (95% CI: 0.59%, 4.29%) in PAI-1, 1.08% (95% CI: 0.21%, 1.96%) in vWF and 1.14% (95% CI: 0.59%, 1.68%) in sP-selectin, respectively. We also found significant associations of short-term exposure to ambient O with PAI-1 (1.62%, 95% CI: 0.01%, 3.25%), sP-selectin (9.59%, 95% CI:2.78%, 16.86%) and t-PA (0.45%, 95% CI: 0.02%, 0.88%), respectively. Short-term exposures to ambient PM, NO and CO were not significantly associated with changes in coagulation biomarkers. In conclusion, short-term exposures to PM and O are associated with significant increases in coagulation biomarkers, suggesting an activated coagulation state upon air pollution exposure.
Topics: Air Pollutants; Air Pollution; Biomarkers; Carbon Monoxide; Environmental Exposure; Nitrogen Dioxide; Ozone; P-Selectin; Particulate Matter; Plasminogen Activator Inhibitor 1; Tissue Plasminogen Activator; von Willebrand Factor
PubMed: 36030918
DOI: 10.1016/j.envres.2022.114210 -
Journal of Clinical Medicine Apr 2021Infection by SARS-CoV-2 is associated with a high risk of thrombosis. The laboratory documentation of hypercoagulability and impaired fibrinolysis remains a challenge.... (Review)
Review
Infection by SARS-CoV-2 is associated with a high risk of thrombosis. The laboratory documentation of hypercoagulability and impaired fibrinolysis remains a challenge. Our aim was to assess the potential usefulness of viscoelastometric testing (VET) to predict thrombotic events in COVID-19 patients according to the literature. We also (i) analyzed the impact of anticoagulation and the methods used to neutralize heparin, (ii) analyzed whether maximal clot mechanical strength brings more information than Clauss fibrinogen, and (iii) critically scrutinized the diagnosis of hypofibrinolysis. We performed a systematic search in PubMed and Scopus databases until 31st December 2020. VET methods and parameters, and patients' features and outcomes were extracted. VET was performed for 1063 patients (893 intensive care unit (ICU) and 170 non-ICU, 44 studies). There was extensive heterogeneity concerning study design, VET device used (ROTEM, TEG, Quantra and ClotPro) and reagents (with non-systematic use of heparin neutralization), timing of assay, and definition of hypercoagulable state. Notably, only 4 out of 25 studies using ROTEM reported data with heparinase (HEPTEM). The common findings were increased clot mechanical strength mainly due to excessive fibrinogen component and impaired to absent fibrinolysis, more conspicuous in the presence of an added plasminogen activator. Only 4 studies out of the 16 that addressed the point found an association of VETs with thrombotic events. So-called functional fibrinogen assessed by VETs showed a variable correlation with Clauss fibrinogen. Abnormal VET pattern, often evidenced despite standard prophylactic anticoagulation, tended to normalize after increased dosing. VET studies reported heterogeneity, and small sample sizes do not support an association between the poorly defined prothrombotic phenotype of COVID-19 and thrombotic events.
PubMed: 33923851
DOI: 10.3390/jcm10081740